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within category "Brain & Neurological"
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Preparing for Prevention of Huntington's Disease (PREVENT-HD) (PREVENT-HD)
This is a prospective investigation which aims to address key challenges to the design of
clinical trials to prevent the onset of Huntington's disease (HD). The project will provide
necessary psychometric data for clinical outcome assessments (COAs) and biomarkers (BMs) in
the cerebral spinal fluid (CSF) to address questions of central importance to the success of
these measures for premanifest clinical trials. Of the 258 participants: 52 will be low risk
of motor diagnosis, 102 high risk of motor diagnosis, 52 with diagnosed HD (stages I or II),
and 52 healthy controls. Participants can expect to be in the study for up to 2 years.
Jane Paulsen
All
18 Years to 80 Years old
NA
This study is also accepting healthy volunteers
NCT04818060
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Inclusion Criteria for HD Participants:
• Estimated at low or high probability of motor diagnosis based on the multivariate risk
score (MRS)
• Willing to commit to two in-person assessment visits (baseline and 2-year follow-up)
and remote assessments as needed
• No active comorbidities (i.e. receiving stable treatment)
• All medications will be allowed although the protocol will mandate documentation of
medications and analyses will particularly assess potential impact of medications on
outcomes (i.e., sedation of abnormal movements)
• If previously measured, CAG results must be 36 or above (previous CAG is not a
requirement, but this threshold will be upheld for those participants who have their
CAG scores and/or have them in their medical record).
Inclusion Criteria for Healthy Controls (HC):
• Willing to commit to two in-person assessment visits (baseline and 2-year follow-up)
and remote assessments as needed
• In generally good health
• IQ > 70
• Able to undergo an MRI scan
Exclusion Criteria (for all Participants):
• Evidence of unstable medical or psychiatric illness (including substance abuse)
• History of severe learning disability, mental retardation, or other central nervous
system (CNS) disease or event (e.g., seizures, head trauma, additional neurological
diagnoses)
• Treatment with phenothiazine-derivative antiemetic medications such as
prochlorperazine, metoclopramide, promethazine and Inapsine greater than 3 times per
month
• History of serious alcohol or drug abuse within the past year
• Unable (determined by patient's prescribing doctor) to not take tryptophan, leucine,
niacin or niacinamide-containing dietary supplements, anti-inflammatory medications,
anti-coagulants (such as warfarin and heparin) or anti-platelets (such as aspirin) in
the past 14 days to assure safety during lumbar puncture
• Unable to fast (no food or drink, only water) overnight before the lumbar puncture
A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma
This phase III trial investigates the best dose of vinblastine in combination with
selumetinib and the benefit of adding vinblastine to selumetinib compared to selumetinib
alone in treating children and young adults with low-grade glioma (a common type of brain
cancer) that has come back after prior treatment (recurrent) or does not respond to therapy
(progressive). Selumetinib is a drug that works by blocking a protein that lets tumor cells
grow without stopping. Vinblastine blocks cell growth by stopping cell division and may kill
cancer cells. Giving selumetinib in combination with vinblastine may work better than
selumetinib alone in treating recurrent or progressive low-grade glioma.
Kenneth Desantes, M.D.
All
2 Years to 25 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04576117
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Inclusion Criteria:
• Feasibility phase: patients must be >= 2 years and =< 21 years of age at the time of
enrollment
• Efficacy phase: patients must be >= 2 years and =< 25 years of age at the time of
enrollment
• All patients > 21 years of age at the time of enrollment must have had initial
diagnosis of low-grade glioma by 21 years of age
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have eligibility confirmed by rapid central pathology and central
molecular screening reviews performed on APEC14B1
• Non-neurofibromatosis type 1 (non-NF1), non-tuberous sclerosis complex (non-TSC)
low-grade glioma (LGG) without a BRAFV600E or IDH1 mutation
• Patients must have progressive or recurrent LGG. Note: Biopsy may be at either
initial diagnosis or recurrence
• Patients must have measurable disease, defined as having a two-dimensional
measurable tumor volume of >= 1 cm^2
• Tumor size will be measured to include both solid and cystic components of
the tumor (whether or not tumor is enhancing) + fluid attenuated inversion
recovery (FLAIR) signal
• Eligible histologies will include all tumors considered low-grade glioma or
low-grade astrocytoma (World Health Organization [WHO] grade 1 and II) by the WHO
Classification of Tumors of the Central Nervous System •4th Edition Revised,
with the exception of subependymal giant cell astrocytoma
• Patients with metastatic disease or multiple independent primary LGGs are
eligible
• Patients must be progressive or recurrent after having been treated with at least one
prior tumor-directed therapy before enrollment
• Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry
onto this study (4 weeks if prior nitrosourea);
• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy
with a biologic agent;
• Radiation therapy (RT): >= 2 weeks (wks) for local palliative RT (small port); >=
6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of
pelvis; >= 6 wks must have elapsed if other substantial bone marrow (BM)
radiation;
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to =< grade 1;
• MEK inhibitor or vinblastine: Must not have received treatment with a MEK
inhibitor or vinblastine within 6 months of study enrollment
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^ 2 or a serum creatinine based on age/gender as follows (within 7 days
prior to enrollment):
• 2 to < 6 years: 0.8 mg/dL (male) 0.8 mg/dL (female)
• 6 to < 10 years: 1 mg/dL (male) 1 mg/dL (female)
• 10 to < 13 years: 1.2 mg/dL (male) 1.2 mg/dL (female)
• 13 to < 16 years: 1.5 mg/dL (male) 1.4 mg/dL (female)
• >= 16 years: 1.7 mg/dL (male) 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study
regardless of their total and indirect [unconjugated] bilirubin levels as long as
their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
(within 7 days prior to enrollment)
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L
• Albumin >= 2 g/L (within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF
result is given as a range of values, then the upper value of the range will be used)
by echocardiogram (within 4 weeks prior to enrollment)
• Corrected QT interval (QTc interval) =< 450 msec by electrocardiogram (EKG) (within 4
weeks prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (within 7 days prior to
enrollment)
• Platelets >= 100,000/uL (unsupported) (within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should not have
experienced a significant increase in seizure frequency within 2 weeks prior to
enrollment
• Stable neurological examination for >= 1 week
• HYPERTENSION:
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile
for age, height, and gender at the time of enrollment (with or without the use of
anti-hypertensive medications);
• Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time
of enrollment (with or without the use of anti-hypertensive medications)
• Note for patients of all ages: Adequate blood pressure can be achieved using
medication for the treatment of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks
prior to enrollment
• For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors)
and/or spine (depending on the site[s] of primary disease) with and without contrast
must be performed within 4 weeks prior to enrollment
• Note: If surgical resection or biopsy is performed at the time of progression or
recurrence, a post-operative MRI is required
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Patients must have the ability to swallow whole capsules
Exclusion Criteria:
• Prior therapy with vinblastine and/or a MEK inhibitor is permitted, with the following
exceptions:
• Patients must not have had progressive disease while on therapy with vinblastine
or a MEK inhibitor;
• Patients must not have discontinued vinblastine or selumetinib due to toxicity
• Patients with a concurrent malignancy or history of treatment (other than surgery) for
another tumor within the last year are ineligible
• Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons
involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
• Patients may not be receiving any other investigational agents
• Patients must not have known hypersensitivity to selumetinib, vinblastine, or similar
compounds
• CYP3A4 agents: Patients must not have received fluconazole or drugs that are strong
inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment
• Patients with any serious medical or psychiatric illness/condition, including
substance use disorders or ophthalmological conditions, likely in the judgment of the
investigator to interfere or limit compliance with study requirements/treatment
• Patients who, in the opinion of the investigator, are not able to comply with the
study procedures are not eligible
• PRE-EXISTING CONDITIONS (CARDIAC):
• Known genetic disorder that increases risk for coronary artery disease. Note: The
presence of dyslipidemia in a family with a history of myocardial infarction is
not in itself an exclusion unless there is a known genetic disorder documented;
• Symptomatic heart failure
• New York Heart Association (NYHA) class II-IV prior or current
cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• PRE-EXISTING CONDITIONS (OPHTHALMOLOGIC CONDITIONS):
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular
pressure (IOP) > 22 mmHg or upper limit of normal (ULN) adjusted by age are
not eligible
• Any multivitamin containing vitamin E must be stopped prior to study enrollment even
if it contains less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of a surgical biopsy,
placement of a vascular access device or cerebrospinal fluid (CSF) diverting procedure
such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt
• Note: Patients must have healed from any prior surgery
• Patients who have an uncontrolled infection are not eligible
• Female patients who are pregnant are not eligible since fetal toxicities and
teratogenic effects have been noted for several of the study drugs. A pregnancy test
is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation and for
12 weeks after stopping study therapy are not eligible
• Note: Women of child-bearing potential and males with sexual partners who are
pregnant or who could become pregnant (i.e., women of child-bearing potential)
should use effective methods of contraception for the duration of the study and
for 12 weeks after stopping study therapy to avoid pregnancy and/or potential
adverse effects on the developing embryo
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Recurrent Low Grade Astrocytoma, Recurrent WHO Grade 2 Glioma, Refractory Low Grade Astrocytoma, Refractory Low Grade Glioma, Refractory WHO Grade 1 Glioma, Brain and Nervous System, Brain/Central Nervous System
Study of TJ033721 in Subjects With Advanced or Metastatic Solid Tumors
This is an open label, multi-center, multiple dose Phase 1 study to evaluate the safety,
tolerability, MTD PK, and PD of TJ033721 in subjects with advanced or metastatic solid
tumors.
Jeremy Kratz, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04900818
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Inclusion Criteria:
• Subjects with advanced or metastatic solid tumor in subjects whose disease has
progressed despite standard therapy, or who has no further standard therapy, or who is
unsuitable for available standard treatment options.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with adequate
organ function
• Have known PD-L1 status with prior testing by immunohistochemistry and a corresponding
combined positive score (CPS)
For dose expansion study only:
• Advanced or metastatic gastric cancer, gastroesophageal junction carcinoma, and
esophageal adenocarcinoma without further standard therapy or unsuitable for available
standard treatment options.
• Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay
Exclusion Criteria
• Prior exposure to CLDN18.2 -targeted therapy
• Prior exposure to 4-1BB agonists
• Second malignancy within the last 3 years with the exception of cutaneous squamous
cell carcinoma or cutaneous basal cell carcinoma or cervical carcinoma in situ
• Known active or chronic Hepatitis B or Hepatitis C, other hepatitides
• Unstable/active ulcer or digestive tract bleeding within 6 weeks
• Active autoimmune disease requiring systemic treatment within the past 2 years
• Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or
pneumonitis requiring treatment
• Known active CNS metastases and/or carcinomatous meningitis. Subjects with previously
treated brain metastases may participate provided they are clinically stable and
without requirement of steroid treatment for at least 14 days prior to first dose of
study treatment;
• New York Heart Association (NYHA) Class 3 or 4 congestive heart failure,
severe/unstable angina, myocardial infarction (MI), symptomatic congestive heart
failure, cerebrovascular accident, transient ischemic attack (TIA), arterial embolism,
pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), deep vein
thrombosis, or coronary artery bypass grafting (CABG) in the previous 6 months
• Diagnosis of immunodeficiency such as known active HIV
• Any active infection requiring parenteral treatment
Solid Tumor, Advanced Cancer, Metastatic Cancer, Gastric Cancer, Gastroesophageal Junction Carcinoma, Esophageal Adenocarcinoma, Lip, Oral Cavity and Pharynx, Esophagus, Colon, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Melanoma, Skin, Kaposi's Sarcoma, Breast, Cervix, Corpus Uteri, Other Female Genital, Other Male Genital, Kidney, Eye and Orbit, Brain and Nervous System, Other Endocrine System, Ill-Defined Sites, Anal, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Ovary, Sarcoma, Uterus
Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)
The purpose of this study is to find out whether the study drug, LY3537982, is safe and
effective in cancer patients who have a specific genetic mutation (KRAS G12C). Patients must
have already received or were not able to tolerate the standard of care, except for specific
groups who have not had cancer treatment. The study will last up to approximately 4 years.
Dustin Deming, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04956640
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Inclusion Criteria:
• Patients have measurable disease per Response Evaluation Criteria in Solid Tumors
version 1.1 (RECIST v1.1).
• Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or
circulating tumor deoxyribonucleic acid (DNA).
• Participants must have a histological or a cytologically proven diagnosis of locally
advanced, unresectable, and/or metastatic cancer and meet cohort-specific criteria.
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Have adequate organ function.
• Have discontinued all previous treatments for cancer with resolution of any
significant ongoing adverse events (AEs), (except in certain scenarios).
• Must be able to swallow capsule/tablet.
• Agree and adhere to contraceptive use, if applicable.
• For some parts of the study, (i.e., one of the two arms with LY3537982 in combination
with pembrolizumab and the arm of LY3537982 in combination with pembrolizumab,
pemetrexed, and platinum therapy) histologically or cytologically confirmed Stage
IIIB-IIIC or Stage IV NSCLC that is previously untreated in the advanced/metastatic
setting and not suitable for curative intent radical surgery or radiation therapy.
Previously untreated patients who received adjuvant and neoadjuvant therapy are
eligible if the last dose of the systemic treatment was completed at least 6 months
prior to enrollment. For untreated patients in the arm with LY3537982 in combination
with pembrolizumab noted above, a single cycle of pembrolizumab may be initiated
within 21 days prior to enrollment. For untreated patients in the arm of LY3537982 in
combination with pembrolizumab, pemetrexed, and platinum therapy, a single cycle of
any or all of the drugs other than LY3537982 may be initiated within 21 days prior to
enrollment. Start of study treatment may be delayed to allow sufficient time for
recovery from treatment-related toxicity.
• For one part of the study, participants must have received at least one prior
oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC.
Exclusion Criteria:
• Disease suitable for local therapy administered with curative intent.
• Have an active, ongoing, or untreated infection.
• Have a serious pre-existing medical condition(s) that, in the judgment of the
investigator, would preclude participation in this study.
• Have a serious cardiac condition.
• Have a second active primary malignancy or have been diagnosed and/or treated for an
additional malignancy within 3 years prior to enrollment.
• Have symptomatic central nervous system (CNS) malignancy or metastasis and/or
carcinomatous meningitis. Patients with treated CNS metastases are eligible for this
study if their disease is asymptomatic, radiographically stable for at least 30 days,
and they do not require treatment with steroids in the two-week period prior to study
treatment. This only applies to some parts of the study.
• Have received prior treatment with any KRAS G12C small molecule inhibitor, except in
certain scenarios where such prior therapy is allowed as per protocol.
• The following patients will be excluded from some parts of the study:
• Experienced certain serious side effects with prior immunotherapy.
• Have an active autoimmune disease that has required systemic anti-autoimmune
treatment in the past 2 years.
• Have received a live vaccine within 30 days prior to the first dose of study
drug.
• Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the trial through 180 days after the last dose of study
medication.
• Known allergic reaction against any of the components of the study treatments.
Lip, Oral Cavity and Pharynx, Esophagus, Colon, Anus, Liver, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Melanoma, Skin, Kaposi's Sarcoma, Breast, Cervix, Corpus Uteri, Other Female Genital, Other Male Genital, Kidney, Eye and Orbit, Brain and Nervous System, Other Endocrine System, Ill-Defined Sites, Anal, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Ovary, Sarcoma, Uterus, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Endometrial Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Biliary Tract Neoplasms
Effect on Body Movement and Mental Skills in Patients Who Received Gadolinium-based Contrast Media for Magnetic Resonance Examination Multiple Times Within 5 Years (ODYSSEY)
This study is a postmarketing requirement jointly carried out by four NDA holders (Bayer AG,
Bracco, GE Healthcare and Guerbet) and the CRO IQVIA.
The study aims to create detailed images of the organs and tissue of the human body during
x-ray, CT-scan or MRI investigations, doctors are using contrast media (a kind of dye) which
can be given to patients by injection into a blood vessel or by mouth.
In this study researchers want to find out whether so called gadolinium-based contrast agents
(GBCAs) have an effect on body movement and mental skills when given to participants multiple
times within 5 years.
The study plans to enroll about 2076 participants suffering from a condition for which they
are likely to have at least annually a MRI or another imaging examinations. Only adults up to
65 years will be considered to join this study. During the study duration of 5 years
participants will receive annually a MRI or other imaging tests (such as CT-scan, x-ray) and
will visit the study doctor at least 7 times for physical examinations, laboratory
investigations and tests on body movement and mental skills.
Richard Bruce, MD
All
18 Years to 64 Years old
Phase 4
This study is NOT accepting healthy volunteers
NCT04373564
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Inclusion Criteria:
• Participant must be neurologically normal, defined as free of unstable neurologic and
psychiatric disease as confirmed by a normal neurologic examination at screening
• Participant (GBCA-exposed or controls) agrees to undergo unenhanced magnetic resonance
imaging (UE-MRI) of the brain at enrollment and at the end of the observation period
(5 years)
• Participants should have at least 1 of the following indications: a) Medium to high
risk for breast cancer or dense breasts undergoing breast cancer screening with MRI,
b) Elevated prostate-specific antigen (PSA) and under active diagnostic surveillance
for prostate cancer, c) Chronic liver disease (eg, liver cirrhosis limited to Child
class A, post-hepatitis chronic hepatopathy, or primary sclerosing cholangitis) for
surveillance of hepatocellular carcinoma development, d) Low-grade colorectal cancer
or neuroendocrine tumor undergoing screening for liver metastases or e) Branch-duct
intraductal papillary mucinous neoplasm (IPMN) of the pancreas (maximum size ≤2 cm)
undergoing imaging surveillance.
In addition, for participants in the GBCA Arms only:
• Each participant should be likely to undergo ≥5 GBCA-enhanced MR examinations with the
same GBCA at least annually throughout the 5-year study duration
• Prospective participants with up to 3 well documented GBCA administrations prior to
study screening are acceptable, provided that the imaging was performed with the same
GBCA as the one to be prospectively used in the study. If the GBCA used cannot be
identified, he/she cannot be enrolled.
For the Control Arm:
• Participants who never had and are not likely to receive any GBCA injection during the
course of the study
• Each control participant must be willing to undergo UE-MRI of the brain at baseline
and at Year 5. In Years 1 to 4, the control participants will undergo their clinically
indicated UE-MRIs, computed tomography (CT), ultrasound, or X-ray procedures
Exclusion Criteria:
• As evidenced by history or determined in the neurologic exam at screening, concurrent
neurological and/or psychiatric disease (or treatments) that could influence the
results of the study's motor and cognitive tests (e.g. Cerebrovascular disease,
Multiple sclerosis, Neurodegenerative disease, Malignant disease other than listed in
indications, Carcinoid tumors, Epilepsy, Prior neurosurgery, Psychotic disorders or
any prior psychotic episode not otherwise specified •any documented prior history of
chronic schizophrenia, Remittent or current medically confirmed major depressive
disorder or bipolar disorder, History of long-term major depression or bipolar
affective disorder with an active episode in the past 2 to 5 years, Neurodevelopmental
disorders (eg, trisomy 21), Uncontrolled severe migraine, Uncontrolled or controlled
anxiety or depression within 6 months before enrollment, Screening scores of ≤24 on
the MMSE and/or ≥11 on the Hospital Anxiety and Depression Scale (HADS)).
• Prior, planned, or ongoing chemotherapy or brain irradiation
• Use of concomitant medication(s) affecting neuro-cognitive or motor function
• Substance or alcohol abuse as determined by the investigator
• Alcoholic cirrhosis
• Renal disease, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73
m2
• History of environmental/occupational/other exposure to one or more chemicals that may
affect cognitive and/or motor function, including, but not limited to, heavy metals
(arsenic [As], cadmium [Cd], lead [Pb], manganese [Mn], and mercury [Hg]), pesticides,
solvents, or carbon monoxide.
• Clinical indications requiring >1 contrast enhanced magnetic resonance imaging
(CE-MRI) every 6 months
• Pregnant or nursing (lactating) women
• Presence of any metal-containing joint implants/prostheses
In addition, for participants in either of the GBCA Arms only:
•Receipt of a GBCA or generic prior to study entry other than the specific GBCA to be
administered during the course of the study.
For participants in the Control Arm only:
• Participants with any previous exposure to a GBCA.
• Participants with any contraindication to UE-MRI examinations.
Motor Function, Cognitive Function, Contrast Media, Breast
Study of GS-1811 Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors
This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine
the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GS-1811 as
monotherapy and in combination with zimberelimab in participants with advanced solid tumors.
This study will be conducted in 6 parts (Parts A, B, and E: monotherapy, Parts C and D:
combination therapy, and Part F for both monotherapy and combination therapy) in participants
with advanced solid tumors who have received, been intolerant to, or been ineligible for all
treatments known to confer clinical benefit or in participants with select solid tumors.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05007782
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Key
Inclusion Criteria:
• Disease:
• Part A: Individuals with histologically or cytologically confirmed advanced solid
tumors who have received, been intolerant to, or been ineligible for all
treatment known to confer clinical benefit.
• Part B: Individuals with histologically or cytologically confirmed select
indications who have received, been intolerant to, or been ineligible for all
treatment known to confer clinical benefit.
• Part C: Individuals with histologically or cytologically confirmed advanced solid
tumors who have received, been intolerant to, or been ineligible for all
treatments known to confer clinical benefit or whose disease is indicated for
anti- programmed cell death protein 1 or programmed cell death ligand 1 (PD-[L]1)
monoclonal antibody monotherapy.
• Part D: Individuals with pathologically confirmed select advanced solid tumors.
• Part E: Individuals with pathologically confirmed select advanced solid tumors.
Participants must have received, have been intolerant to, or have been ineligible
for all treatment known to confer clinical benefit.
• Part F: Individuals with pathologically-confirmed select advanced solid tumors.
Participants must have received, have been intolerant to, or have been ineligible
for all treatments known to confer clinical benefit; or, for participants who
will undergo combination therapy, have disease which is indicated for
anti-PD-(L)1 mAb monotherapy.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for
individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D, E, and F.
• Adequate organ function.
• Male individuals and female individuals of childbearing potential who engage in
heterosexual intercourse must agree to use methods of contraception.
• Tissue requirement:
• Parts A, C, D, E and F: Must provide pre-treatment adequate tumor tissue sample
prior to enrollment.
• Part B and select participants in Parts C and F: Must have fresh pre-treatment
and on-treatment biopsies for biomarker analysis.
Key
Exclusion Criteria:
• Concurrent anticancer treatment.
• Any anti-cancer therapy, whether investigational or approved, within protocol
specified time prior to initiation of study including: immunotherapy or biologic
therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14
days), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21
days).
• Any prior CCR8 directed therapy.
• Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell
transplantation. Exception: prior corneal transplant without requirement for systemic
immunosuppressive agents is allowed.
• Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected
carcinoma in situ, localized prostate cancer, or superficial bladder cancer after
undergoing potentially curative therapy with no evidence of disease. Individuals with
other previous malignancies are eligible if disease-free for > 2 years.
• History of intolerance, hypersensitivity, or treatment discontinuation due to severe
immune-related adverse events (irAEs) on prior immunotherapy.
• History of autoimmune disease or active autoimmune disease requiring systemic
treatment within 2 years.
• History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis
(excluding localized radiation pneumonitis).
• Active and clinically relevant bacterial, fungal, or viral infection that is not
controlled or requires IV antibiotics.
• Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human
immunodeficiency virus (HIV).
• Positive serum pregnancy test or breastfeeding female.
• Live vaccines within 30 days prior to first dose.
• Significant cardiovascular disease.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Advanced Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Study of DF1001 in Patients With Advanced Solid Tumors
DF1001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell
activation signals to specific receptors on cancer cells. The study will occur in two phases.
The first phase will be a dose escalation phase, enrolling patients with various types of
solid tumors that express human epidermal growth factor receptor 2 (HER2). The second phase
will include a dose expansion using the best dose selected from the first phase of the study.
Multiple cohorts will be opened with eligible patients having either HER2 activated non-small
cell lung cancer, hormone receptor (HR) positive HER2 negative metastatic breast cancer, or
HER2 positive metastatic breast cancer. DF1001-001 will be administered as monotherapy or in
combination; combinations are DF1001 + nivolumab, DF1001 + Nab paclitaxel, and DF1001 +
sacituzumab govitecan-hziy.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04143711
Show full eligibility criteria
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Inclusion Criteria:
General (applies to all cohorts)
1. Signed written informed consent.
2. Male or female patients aged ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry
and an estimated life expectancy of at least 3 months.
4. Baseline Left Ventricular Ejection Fraction (LVEF) ≥ 55% measured by echocardiography
(preferred) or multigated acquisition (MUGA) scan.
5. Adequate hematological function.
6. Adequate hepatic function.
7. Adequate renal function.
8. Effective contraception for women of child bearing potential (WOCBP) patients as
defined by World Health Organization (WHO) guidelines for 1 "highly effective" method
or 2 "effective" methods.
Inclusion Criteria:
NSCLC (HER2 Activated) Exploratory Efficacy Cohorts •Monotherapy and
Combination with Sacituzumab Govitecan-hziy.
1. Have progression of unresectable locally advanced or metastatic NSCLC after last
systemic therapy (as confirmed by investigator) or be intolerant of last systemic
therapy.
2. Have HER2 overexpression status (IHC 2+ or 3+), or ERBB2 amplification, or HER2
activating mutation
3. Have recurrent or progressive disease during or after platinum doublet-based
chemotherapy.
4. Have received and progressed on or after anti-PD-(L)1 therapy.
Inclusion Criteria:
Metastatic Breast Cancer (HR+/HER2-) Exploratory Efficacy Cohort -
Monotherapy and Combination with Sacituzumab Govitecan-hziy.
1. Documented evidence of HR+ metastatic breast cancer
2. Documented evidence of HER2- status.
3. Disease progression or recurrence after prior therapy.
Inclusion Criteria:
Metastatic Breast Cancer (HER2+) Exploratory Efficacy Cohorts -
Combination with Sacituzumab Govitecan-hziy
1. Have histologically confirmed HER2+ breast cancer.
2. Have received prior treatment with trastuzumab, pertuzumab, ado-trastuzumab emtansine
(T-DM1), or trastuzumab deruxtecan (T-DXd).
3. Have progression of unresectable locally advanced metastatic breast cancer after last
systemic therapy or be intolerant of last systemic therapy.
Inclusion Criteria:
Dose Escalation
1. Evidence of objective disease, but participation does not require a measurable lesion.
2. Locally advanced or metastatic solid tumors, for which no standard therapy exists, or
standard therapy has failed.
3. HER2 expression by immunohistochemistry and/or erbb2 amplification and/or erbb2
activating mutations.
Inclusion Criteria:
"3+3" Nivolumab Combination Cohort
1. Eligible to receive nivolumab per its label for a malignancy of epithelial origin; or
2. Have no standard therapy available, or standard therapy has failed, and must not have
received nivolumab prior to joining the study.
3. HER2 expression by immunohistochemistry and/or ebb2 amplification and/or erbb2
activating mutations must be documented on either archival tissue or fresh tumor
biopsy.
Inclusion Criteria:
"3+3" Nab paclitaxel Combination Cohort
1. Patients must be eligible for treatment with nab-paclitaxel per its label, or have no
standard therapy available, or standard therapy has failed.
2. HER2 expression by immunohistochemistry and/or erbb2 amplification and/or erbb2
activating mutations must be documented on either archival tissue or fresh tumor
biopsy.
Inclusion Criteria:
Safety/PK/PD Expansion Cohorts (Monotherapy and Combination Therapy).
1. Fresh tumor biopsy must be obtained during the screening window.
2. HER2 expression by immunohistochemistry (IHC).
3. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
Inclusion Criteria:
Urothelial Bladder Cancer Expansion Cohort(s).
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically or cytologically documented locally advanced or metastatic transitional
cell carcinoma of the urothelium (including renal pelvis, ureters, urinary urothelial,
urethra).
3. Patients must have received a platinum containing chemotherapy and an anti PD-1 or
anti PD-L1 for the treatment of urothelial bladder cancer.
Inclusion Criteria:
Breast Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1
2. Histologically documented (metastatic or locally advanced) breast cancer.
3. Absence of erbb2 amplification by ISH and/or HER2 IHC of 0, 1+, or 2+.
4. Patient must have progressed after one line of systemic chemotherapy.
Inclusion Criteria:
Breast Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1
2. Histologically documented (metastatic or locally advanced) breast cancer.
3. Erbb2 amplification by ISH and/or HER2 IHC of 3+, or 2+. If Herceptest score is 2+,
ISH results should demonstrate erbb2 amplification.
Inclusion Criteria:
Basket erbb2 amplified Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Documented history of erbb2 amplification.
3. Patients must have received at least one line of an approved or established therapy.
Inclusion Criteria:
Gastric Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) gastric cancer or cancer of the
gastro-esophageal junction.
3. Tumor must have been declared HER2 positive.
Inclusion Criteria:
Gastric Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) gastric cancer or cancer of the
gastro-esophageal junction.
3. Tumor must have been declared HER2 low; ISH non-amplified and/or HER2 IHC of 0, 1+ or
2+. If Herceptest score is 0, HER2 must be detected by IHC on at least 1+ of the tumor
cells.
Inclusion Criteria:
Esophageal Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) esophageal cancer.
3. Tumor must have been declared HER2 positive.
Inclusion Criteria:
Esophageal Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) esophageal cancer.
3. Tumor must have been declared HER2 low; ISH non-amplified and/or HER2 IHC of 0, 1+ or
2+. If Herceptest score is 0, HER2 must be detected by IHC on at least 1+ of the tumor
cells.
Inclusion Criteria:
Non-small Cell Lung Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or
recurrent disease that has been confirmed to have HER2 expression (at least 1+,
however, patients must not carry an erbb2 amplification) via archival or fresh biopsy
tissue prior to study enrollment.
3. Patients must have recurrent or progressive disease during or after platinum
doublet-based chemotherapy.
Inclusion Criteria:
Non-small Cell Lung Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or
recurrent disease that has been confirmed to have amplification of erbb2 via archival
or fresh biopsy tissue prior to study enrollment.
3. Patients must have recurrent or progressive disease during or after platinum
doublet-based chemotherapy.
Exclusion Criteria:
1. Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy [with the
exception of palliative bone directed radiotherapy], immune therapy, or cytokine
therapy except for erythropoietin), major surgery (excluding prior diagnostic biopsy),
concurrent systemic therapy with steroids or other immunosuppressive agents, or use of
any investigational drug within 28 days or 5 half-lives before the start of study
treatment. Note: Patients receiving bisphosphonates are eligible provided treatment
was initiated at least 14 days before the first dose of DF1001.
2. Previous malignant disease other than the target malignancy to be investigated in this
study within the last 3 years, with the exception of basal or squamous cell carcinoma
of the skin or cervical carcinoma in situ.
3. Rapidly progressive disease.
4. Active or history of central nervous system (CNS) metastases.
5. Receipt of any organ transplantation including autologous or allogeneic stem-cell
transplantation.
6. Significant acute or chronic infections (including historic positive test for human
immunodeficiency virus [HIV], or active or latent hepatitis B or active hepatitis C
tested during the screening window).
7. Preexisting autoimmune disease (except for patients with vitiligo) needing treatment
with systemic immunosuppressive agents for more than 28 days within the last 3 years
or clinically relevant immunodeficiencies (eg, dys-gammaglobulinemia or congenital
immunodeficiencies), or fever within 7 days of Day 1.
8. Known severe hypersensitivity reactions to mAbs (≥ Grade 3 NCI-CTCAE v5.0), any
history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partly
controlled asthma).
9. Persisting toxicity related to prior therapy > Grade 1 NCI-CTCAE v5.0, however
alopecia and sensory neuropathy ≤ Grade 2 is acceptable.
10. Pregnancy or lactation in females during the study.
11. Known alcohol or drug abuse.
12. Serious cardiac illness
13. NYHA III of IV heart failure or systolic dysfunction (LVEF < 55%)
14. High-risk uncontrolled arrhythmias ie, tachycardia with a heart rate > 100/min at rest
15. Significant ventricular arrhythmia (ventricular tachycardia) or higher-grade
Atrioventricular block (AV-block; second-degree AV-block Type 2 [Mobitz 2] or
third-degree AV-block)
16. Angina pectoris requiring anti-anginal medication
17. Clinically significant valvular heart disease
18. Evidence of transmural infarction on ECG
19. Poorly controlled hypertension (defined by: systolic > 180 mm Hg or diastolic > 100 mm
Hg)
20. Clinically relevant uncontrolled cardiac risk factors, clinically relevant pulmonary
disease or any clinically relevant medical condition in the opinion of the
Investigator that may limit participation in this study.
21. Severe dyspnea at rest due to complications of advanced malignancy or requiring
supplementary oxygen therapy.
22. All other significant diseases (e.g., inflammatory bowel disease), which, in the
opinion of the Investigator, might impair the patient's ability to participate
23. Any psychiatric condition that would prohibit the understanding or rendering of
informed consent.
24. Legal incapacity or limited legal capacity.
25. Incapable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol .
Solid Tumor, Adult, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Testing if High Dose Radiation Only to the Sites of Brain Cancer Compared to Whole Brain Radiation That Avoids the Hippocampus is Better at Preventing Loss of Memory and Thinking Ability
This phase III trial compares the effect of stereotactic radiosurgery to standard of care
memantine and whole brain radiation therapy that avoids the hippocampus (the memory zone of
the brain) for the treatment of small cell lung cancer that has spread to the brain.
Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high
dose of radiation directly to the tumor and may cause less damage to normal tissue. Whole
brain radiation therapy delivers a low dose of radiation to the entire brain including the
normal brain tissue. Hippocampal avoidance during whole-brain radiation therapy (HA-WBRT)
decreases the amount of radiation that is delivered to the hippocampus which is a brain
structure that is important for memory. The drug, memantine, is also often given with whole
brain radiotherapy because it may decrease the risk of side effects related to thinking and
memory. Stereotactic radiosurgery may decrease side effects related to memory and thinking
compared to standard of care HA-WBRT plus memantine.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04804644
Show full eligibility criteria
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Inclusion Criteria:
• Pathologically (histologically or cytologically) proven diagnosis of small cell lung
cancer within 5 years of registration. If the original histologic proof of malignancy
is greater than 5 years, then pathological (i.e., more recent) confirmation is
required (e.g., from a systemic or brain metastasis);
• Patients with de novo or recurrent small cell lung cancer are permitted.
• Ten or fewer brain metastases ≤ 3 cm in largest diameter and outside a 5-mm margin
around either hippocampus must be visible on contrast-enhanced magnetic resonance
imaging (MRI) performed ≤ 21 days prior to study entry.
• Brain metastases can be diagnosed synchronous to the initial diagnosis of small
cell lung cancer or metachronous to the initial diagnosis and management of small
cell lung cancer.
• The total tumor volume must be 30 cm^3 or less. Lesion volume will be
approximated by measuring the lesion's three perpendicular diameters on contrast
enhanced, T1-weighted MRI and the product of those diameters will be divided by 2
to estimate the lesion volume (e.g. xyz/2). Alternatively, direct volumetric
measurements via slice by slice contouring on a treatment planning software
package can be used to calculate the total tumor volume.
• Brain metastases must be diagnosed on MRI, which will include the following
elements:
• REQUIRED MRI ELEMENTS
• Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D)
spoiled gradient (SPGR). Acceptable 3D SPGR sequences include
magnetization prepared 3D gradient recalled echo (GRE) rapid gradient
echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (Brain Volume
Imaging) or 3D Fast FE (field echo). The T1-weighted 3D scan should use
the smallest possible axial slice thickness, not to exceed 1.5 mm.
• Pre-contrast T1 weighted imaging (3D imaging sequence strongly
encouraged).
• A minimum of one axial T2 FLAIR (preferred) or T2 sequence is required.
This can be acquired as a two dimensional (2D) or 3D image. If 2D, the
images should be obtained in the axial plane.
• ADDITIONAL RECOMMENDATIONS
• Recommendation is that an axial T2 FLAIR (preferred) sequence be
performed instead of a T2 sequence.
• Recommendation is that that pre-contrast 3D T1 be performed with the
same parameters as the post-contrast 3D T1.
• Recommendation is that imaging be performed on a 3 Tesla (3T) MRI.
• Recommendation is that the study participants be scanned on the same
MRI instrument at each time point.
• Recommendation is that if additional sequences are obtained, these
should meet the criteria outlined in Kaufmann et al., 2020.
• If additional sequences are obtained, total imaging time should not
exceed 60 minutes.
• History/physical examination
• Age ≥ 18
• Karnofsky performance status of ≥ 70
• Creatinine clearance ≥ 30 ml/min
• Following the diagnosis of brain metastases, patients can initiate and treat with
systemic (chemotherapy and/or immunotherapy) before enrollment only if their brain
metastases are asymptomatic and not located in eloquent locations (e.g., brainstem,
pre-/post-central gyrus, visual cortex). However, within 21 days prior to enrollment,
brain MRI must be repeated to confirm eligibility.
• Patients with symptomatic brain metastases and/or brain metastases in eloquent
locations (e.g., brainstem, pre-/post central gyrus, visual cortex) are eligible
for enrollment on the trial; however, the specific treatment approach of starting
with systemic therapy alone and delaying brain radiation is not recommended for
these patients.
• Concurrent immunotherapy with brain radiation (SRS or HA-WBRT) is permitted.
• Negative urine or serum pregnancy test (in women of childbearing potential) within 14
days prior to registration. Women of childbearing potential and men who are sexually
active must use contraception while on study.
• Patients may have had prior intracranial surgical resection. Patients must have
completed prior intracranial surgical resection at least 14 days prior to
registration.
• Because neurocognitive testing is the primary goal of this study, patients must be
proficient in English or French Canadian.
• The patient must provide study-specific informed consent prior to study entry.
• Patients with impaired decision-making capacity are not permitted on study.
• ELIGIBILITY CRITERIA PRIOR TO STEP 2 REGISTRATION
• The following baseline neurocognitive tests must be completed within 21 days prior to
Step 2 registration: HVLT-R, TMT, and COWA. The neurocognitive test will be uploaded
into RAVE for evaluation by Dr. Wefel. Once the upload is complete, within 3 business
days a notification will be sent via email to the RA to proceed to Step 2.
• NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step
1 registration.
Exclusion Criteria:
• Planned infusion of cytotoxic chemotherapy on the same day as SRS or HA-WBRT
treatment. Patients may have had prior chemotherapy. Concurrent immunotherapy is
permitted.
• Prior allergic reaction to memantine.
• Intractable seizures while on adequate anticonvulsant therapy; more than 1 seizure per
month for the past 2 months.
• Patients with definitive leptomeningeal metastases.
• Known history of demyelinating disease such as multiple sclerosis.
• Contraindication to MR imaging such as implanted metal devices that are
MRI-incompatible, allergy to MRI contrast that cannot be adequately addressed with
pre-contrast medications, or foreign bodies that preclude MRI imaging. (Questions
regarding MRI compatibility of implanted objects should be reviewed with the Radiology
Department performing the MRI).
• Current use of (other N-methyl-D-aspartate [NMDA] antagonists) amantadine, ketamine,
or dextromethorphan.
• Radiographic evidence of hydrocephalus or other architectural change of the
ventricular system resulting in significant anatomic distortion of the hippocampus,
including placement of external ventricular drain or ventriculoperitoneal shunt.
• Mild cases of hydrocephalus not resulting in significant anatomic distortion of
the hippocampus are permitted.
• Prior radiotherapy to the brain, including SRS, WBRT, or prophylactic cranial
irradiation (PCI).
• Severe, active co-morbidity defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration
• Chronic obstructive pulmonary disease exacerbation or other acute respiratory
illness precluding study therapy at the time of registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
Metastatic Lung Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Recurrent Lung Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8, Lung
Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)
A Phase 2 multi-center open-label basket trial of nab-sirolimus for adult and adolescent
patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or
TSC2 genes
Dustin Deming, MD
All
12 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05103358
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Patients must have a malignant solid tumor with a pathogenic inactivating TSC1 or TSC2
alteration. Genetic alterations should be identified using NGS in tumor tissue or
liquid biopsy).
• Patients will be enrolled after the central evaluation of NGS report confirms
eligibility.
2. Patients must have solid tumors that are metastatic or locally advanced where surgical
resection is not an option or likely to result in severe morbidity.
3. Patients must have received all standard therapies appropriate for their tumor type
and stage of disease or, in the opinion of the Investigator, the patient would be
unlikely to tolerate or derive clinically meaningful benefit from appropriate standard
of care therapy, or the patient has no satisfactory alternative treatments.
4. Patients must have 1 or more measurable target lesions by computed tomography (CT)
scan or magnetic resonance imaging (MRI) (RECIST v1.1).
5. Age: 12 years or older.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or Karnofsky
Performance Status (KPS) ≥80 or Lansky play-performance scale for pediatric patients
≥80.
7. Adequate liver function:
1. Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's
syndrome, then ≤3 × ULN)
2. Aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if attributable to liver
metastases)
8. Adequate renal function: creatinine clearance ≥30 mL/min, Cockcroft-Gault CCr =
((140-age) × weight[kg]) / (72 × SCr[mL/min]) × 0.85, if female
9. Adequate hematologic parameters:
1. Absolute neutrophil count (ANC) ≥1.0 × 109/L (growth factor support allowed)
2. Platelet count ≥100,000/mm3 (100 × 109/L) (transfusion and/or growth factor
support allowed)
3. Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed)
10. Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be ≤350
mg/dL.
11. Minimum of 4 weeks since any major surgery, completion of radiation, or completion of
prior systemic anticancer therapy, or at least 5 half-lives if the prior therapy is a
single agent small-molecule therapeutic, and adequately recovered from the acute
toxicities of any prior therapy, including neuropathy, to Grade ≤1.
12. Male or non-pregnant and non-breastfeeding female:
1. Females of childbearing potential must agree to use effective contraception or
abstinence without interruption from 28 days prior to starting investigational
product (IP) throughout 3 months after last dose of IP and have a negative serum
pregnancy test (beta human chorionic gonadotropin, β-hCG) result at screening and
agree to ongoing pregnancy testing during the course of the study, and after the
end of study treatment. A second form of birth control is required even if she
has had a tubal ligation.
2. Male patients must agree not to donate sperm and must practice abstinence or
agree to use a condom during sexual contact with a pregnant female or a female of
childbearing potential while participating in the study and throughout 3 months
after last dose of IP. A second form of birth control is required even if he has
undergone a successful vasectomy.
13. The patient or the patient's parent(s) or legal guardian(s) understand(s) and sign(s)
the informed consent.
14. Willingness and ability to comply with scheduled visits, laboratory tests, and other
study procedures.
Exclusion Criteria:
1. Prior treatment with an mTOR inhibitor, including nab-sirolimus.
2. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective
treatment, either ongoing or completed ≤7 days prior to enrollment.
3. Patients with primary brain tumors or PEComa.
4. Patients who have any severe and/or uncontrolled medical or psychiatric conditions or
other conditions that could affect their participation including:
1. Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal
cord compression, untreated brain metastases or symptomatic or unstable brain
metastases. Note: Patients with stable brain metastases (defined as asymptomatic
or no requirement for high-dose [defined as dexamethasone 10 mg daily or higher]
or increasing dose of systemic corticosteroids) and without imminent need of
radiation therapy are eligible. If applicable, patients must have completed brain
radiation therapy and recovered adequately from any associated toxicity and/or
complications prior to eligibility assessment. For patients who have received
prior radiation therapy, post-treatment MRI scan should show no increase in brain
lesion size/volume.
2. Unstable angina pectoris, symptomatic congestive heart failure (New York Heart
Association, NYHA class III or IV), myocardial infarction ≤6 months prior to
first study treatment, serious uncontrolled cardiac arrhythmia or any other
clinically significant cardiac disease.
3. Pre-existing severely impaired lung function. If a patient has a pre-existing
pulmonary condition, eligible patients should have a spirometry and diffusing
capacity for carbon monoxide (DLCO) that is >50% of the normal predicted value
and/or O2 saturation that is >88% at rest on room air (Note: spirometry and
pulmonary function tests [PFTs] not required to be performed unless clinically
indicated).
4. Nonmalignant medical illnesses that are uncontrolled or whose control may be
jeopardized by the treatment with the study therapy.
5. A history of malignancies other than the one under treatment unless the patient
is disease-free for more than 5 years from diagnosis. Note, controlled
non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental
prostate cancer, certain low grade hematologic malignancies (eg CLL, follicular
lymphoma, etc), or other adequately treated carcinoma-in-situ may be eligible,
after discussion with the medical monitor.
6. Uncontrolled hypertension (systolic blood pressure ≥160 mm-Hg and/or diastolic
blood pressure ≥100 mm Hg).
7. Patients with history of interstitial lung disease and/or pneumonitis, or
pulmonary hypertension.
8. Individuals with known human immunodeficiency virus (HIV) infection are excluded
from this study as combination antiretroviral therapy could potentially result in
significant pharmacokinetic interactions. In addition, these individuals are at
increased risk of serious infections due to the immunosuppressive effects of mTOR
inhibition.
9. Active Hepatitis B or Hepatitis C, with detectable viral load.
5. Regarding concomitant medications with significant CYP3A4 and P-gp interactions,
discontinuation of strong inhibitors (eg, ketoconazole, itraconazole, voriconazole,
erythromycin, clarithromycin, telithromycin, and others), strong inducers (eg,
rifampin, rifabutin), and known CYP3A4 substrates with a narrow therapeutic window
(eg, fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide,
quinidine, or terfenadine) is required at least 5 half lives prior to receiving the
first dose of nab-sirolimus, whichever is longer.
Tumor, Tumor, Solid, Metastasis, Metastatic Cancer, Cancer, Cancer Metastatic, Tumors, Neoplasms, Neoplasm Metastasis, Solid Tumor, Advanced Solid Tumor, Advanced Cancer, Malignant Solid Tumor, Malignant Solid Neoplasm, Malignant Neoplasm, Malignant Tumor, TSC, TSC1, TSC2, Metastatic Solid Tumor, Metastatic Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Lung, Melanoma/Skin cancer, Sarcoma, Uterus
A Phase 2b Clinical Study With a Combination Immunotherapy in Newly Diagnosed Patients With Glioblastoma
The purpose of this study is to assess progression-free survival (PFS) and overall survival
(OS) in newly diagnosed Glioblastoma (GBM) participants treated with IGV-001 as compared with
placebo.
Ankush Bhatia, M.D.
All
18 Years to 70 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04485949
Show full eligibility criteria
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Key
Inclusion Criteria:
• Has a Karnofsky performance scale (KPS) score ≥ 70 at screening
• Has a new diagnosis of GBM (WHO GRADE III or Grade IV GBM) based on the treating
neurosurgeon's best clinical judgement
• Has a diagnostic contrast-enhanced magnetic resonance imaging (MRI) scan with fluid
attenuated inversion-recovery (FLAIR) sequence of the brain at screening. Participants
must have a confirmed measurable disease pre-operatively with at least 1 lesion
measuring a total bi-perpendicular product of 4 centimeter square (cm^2) in 2
different planes (axial, sagittal, or coronal)
• The tumor must be located in the supratentorial compartment
• Has adequate bone marrow and organ function at screening
Key
Exclusion Criteria:
• Has bi-hemispheric disease, multicentric disease, or disease burden involving the
brain stem or cerebellum based on MRI post-gadolinium enhancement
• Has received any previous surgical resection or any anticancer intervention for glioma
• Has any history of glioma, a concurrent malignancy, or malignancy within 3 years of
randomization, unless definitive therapy is completed, with the exception of basal or
squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the
cervix or breast that has completed curative therapy
• Has any severe immunocompromised condition (eg, human immunodeficiency virus (HIV)
with a cluster of differentiation [CD] 4+ cell count <200*10^6/liter [L]) or any
active uncontrolled autoimmune disease (eg, Crohn's disease)
• Has an active cardiac disease or a history of cardiac dysfunction
• Is receiving any other investigational agent(s) or has received an investigational
agent within 30 days or 5 half-lives of investigational agent use, whichever is
longer, prior to screening
• Is partaking in another interventional study. Participants who are partaking in an
observational study are eligible
• Has received a live vaccine within 30 days of screening
• Has active and uncontrolled/untreated hepatitis B virus (HBV), hepatitis C virus
(HCV), HIV, or any other active infections that, in the Investigator's opinion, would
impair or prohibit a participant's participation in this study.
• Is receiving treatment with Tumor Treating Fields or Optune®
Brain and Nervous System, Brain/Central Nervous System, Glioblastoma
A Study to See if Memantine Protects the Brain During Radiation Therapy Treatment for Primary Central Nervous System Tumors
This phase III trial compares memantine to usual treatment in treating patients with primary
central nervous system tumors. Memantine may block receptors (parts of nerve cells) in the
brain known to contribute to a decline in cognitive function. Giving memantine may make a
difference in cognitive function (attention, memory, or other thought processes) in children
and adolescents receiving brain radiation therapy to treat a primary central nervous system
tumors.
Kenneth Desantes, M.D.
All
4 Years to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04939597
Show full eligibility criteria
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Inclusion Criteria:
• >= 4 and < 18 years at time of study entry
• Patients must weigh 15 kg or greater at time of study entry
• Primary central nervous system tumors that have not received prior cranial
radiotherapy
• Planned focal, cranial or craniospinal radiation treatment for a primary central
nervous system tumor
• The patient must have receptive and expressive language skills in English, French or
Spanish since the neurocognitive function and quality of life (QOL) assessment
instruments are available in these languages only
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 4 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 male; 0.8 female
• Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 male; 1 female
• Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 male; 1.2 female
• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 male; 1.4 female
• Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 male; 1.4 female
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L
• The patient must be able to undergo magnetic resonance imaging
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Life expectancy of less than 18 months
• Pre-existing conditions:
• Any contraindication or allergy to study drug (memantine or placebo)
• Intractable seizures while on adequate anticonvulsant therapy, defined as more
than one seizure per month for the past 2 months or since initiating
anticonvulsant therapy
• History of neurodevelopmental disorder such as Down syndrome, Fragile X,
William's Syndrome, intellectual disability (presumed intelligence quotient [IQ]
< 70), etc
• Co-morbid systemic illnesses, psychiatric conditions, social situations, or other
severe concurrent disease which, in the judgment of the investigator, would make
the patient inappropriate for entry into this study or interfere significantly
with the proper assessment of safety and toxicity of the prescribed regimens or
would limit compliance with the study requirements
• Patients with a motor, visual, or auditory condition that precludes participation
in computerized neurocognitive assessments
• Patients with any medical condition or taking medications that lead to
alterations of urine pH towards the alkaline condition (e.g., renal tubular
acidosis, carbonic anhydrase inhibitors, sodium bicarbonate)
• Personal history of prior cranial or craniospinal radiotherapy is not allowed
• Note: Prior anti-cancer therapy including surgery, chemotherapy, targeted agents
are allowed as per standard of care clinical treatment guidelines
• Female patients who are pregnant are excluded since fetal toxicities and teratogenic
effects have been noted for the study drug. A pregnancy test is required for female
patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who do not agree to use an
effective contraceptive method for the duration of their study participation
Central Nervous System Carcinoma, Brain and Nervous System, Brain/Central Nervous System
First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Advanced Solid Tumor Patients and in Combination With Fulvestrant in Patients With Advanced Breast Cancer
This is an open-label, FIH study designed to evaluate the maximum tolerated dose, recommended
Phase 2 dose, safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic
activity of RLY-2608, in advanced solid tumor patients with a
Phosphatidylinositol-4,5-bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutation in
blood and/or tumor per local assessment. The study will evaluate RLY-2608 as a single agent
for patients with unresectable or metastatic solid tumors, RLY-2608 + fulvestrant and
RLY-2608 + fulvestrant + CDK4/6 inhibitor (palbociclib or ribociclib) combination arms for
patients with HR+ HER2- locally advanced or metastatic breast cancer. The RLY-2608 single
agent arm, RLY-2608 + fulvestrant combination arm, and triple combination arms will have 2
parts: a dose escalation (Part 1) and a dose expansion (Part 2).
Kari Wisinski, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05216432
Show full eligibility criteria
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Key Inclusion Criteria
Patient has ECOG performance status of 0-1
One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor per local
assessment
•Other potentially oncogenic PIK3CA mutations may be considered but must be approved by
the Sponsor prior to enrollment.
Part 1 •Ability to provide archived tumor tissue or be willing to undergo pretreatment
tumor biopsy to assess PIK3CA status retrospectively Part 2 •Submit tumor tissue prior to
study drug initiation for determination of PIK3CA mutation retrospectively.
Key Inclusion for RLY-2608 Single Agent Arm
• [For Part 1]: Evaluable disease per RECIST v1.1
• [For Part 2]: Measurable disease per RECIST v1.1
• Disease that is refractory to standard therapy, intolerant to standard therapy, or has
declined standard therapy.
• Part 1- histologically or cytologically confirmed diagnosis of unresectable or
metastatic solid tumor
• Part 2 •Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the
following tumor types:
Group 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group 3:
cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian, head
and neck squamous cell, and cervical cancers Group 5: unresectable or metastatic solid
tumors with PIK3CA double mutations
Key Inclusion for Combination Arms
• [For Part 1 and Part 2]: Evaluable disease per RECIST v1.1
• Male or female with histologically or cytologically confirmed diagnosis of HR+, HER2-
unresectable or metastatic breast cancer that is not amenable to curative therapy.
Females may be postmenopausal, premenopausal, or perimenopausal. Premenopausal or
perimenopausal females must have a histologically or cytologically confirmed diagnosis
of HR+ HER2- advanced or metastatic breast cancer that is not amenable to curative
therapy and must have been previously treated with GnRH agonist at least 4 weeks prior
to start of study drug
• [For Part 1 and Part 2]: Had previous treatment for advanced or metastatic breast
cancer with:
1. ≤1 line of chemotherapy,
2. ≥1 cyclin-dependent kinases (CDK) 4/6 inhibitor, and
3. ≥1 antiestrogen therapy including, but not limited to, selective
estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor
modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole,
anastrozole, exemestane), and
4. ≥1 PARP inhibitor, if appropriate, if documented germline BRCA1/2 mutation Note:
Systemic local, loco-regional, or adjuvant treatment is not to be included in
enumeration or previous treatment
[For RLY-2608 + fulvestrant arm; Part 2, Group 2]: Received prior treatment with a PI3Kα
inhibitor and discontinued the inhibitor due to intolerance and not disease progression,
where intolerance is defined as treatment discontinuation due to treatment related AE (eg.
hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction
and/or life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome.
Key Exclusion Criteria
Prior treatment with PI3Kα, AKT, or mTOR inhibitors (except for RLY-2608 + fulvestrant arm,
Part 2, Group 2).
Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose
≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%.
History of hypersensitivity to PI3K inhibitors. For combination arms only: hypersensitivity
to fulvestrant, palbociclib, and/or ribociclib, as appropriate for the combination.
For triple combination arms only: history of pneumonitis or interstitial lung disease.
For the single agent and combination arms other than with ribociclib: mean QT interval
corrected using Fridericia's formula (QTcF) >480 msec. For the combination arms with
ribociclib: mean QTcF ≥450 msec.
Patient has a history of prolonged QT syndrome or torsades de pointes. Patient has a
familial history of prolonged QT syndrome.
Clinically significant, uncontrolled cardiovascular disease CNS metastases or primary CNS
tumor that is associated with progressive neurologic symptoms
PIK3CA Mutation, Solid Tumor, Adult, HER2-negative Breast Cancer, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer, Unresectable Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
A Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases
This phase II trial compares the effect of encorafenib, binimetinib, and nivolumab versus
ipilimumab and nivolumab in treating patients with BRAF- V600 mutant melanoma that has spread
to the brain (brain metastases). Encorafenib and binimetinib may stop the growth of tumor
cells by blocking some of the enzymes needed for cell growth. Ipilimumab and nivolumab are
monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread.
This trial aims to find out which approach is more effective in shrinking and controlling
brain metastases from melanoma.
Vincent Ma, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04511013
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Inclusion Criteria:
• Participants must have histologically and pathologically confirmed melanoma that has
metastasized to the brain
• Any primary (cutaneous, acral/mucosal, etc) or unknown origin are permitted, except
that participants with uveal primary are not eligible
• Participants must have BRAF-V600 mutant melanoma documented by a Clinical Laboratory
Improvement Act (CLIA)-certified laboratory
• All participants must have an magnetic resonance imaging (MRI) of the brain within 28
days prior to registration and must have central nervous system metastases with at
least one measurable brain metastasis >= 0.5 cm in size (per modified RECIST 1.1) that
has not been irradiated, or progressed (in the opinion of the treating physician)
after prior radiation therapy. Participating sites MUST use MRI slice thickness of =<
1.5 mm and are recommended to adhere to the 'minimum' Brain Tumor Imaging Protocol for
Clinical Trials in Brain Metastases (BTIP-BM) compliant MRI acquisition protocol.
Computed tomography (CT) of the head cannot substitute for brain MRI. (NOTE: All
central nervous system [CNS] disease must be documented on BOTH the Brain Metastases
Baseline Tumor Assessment Form, using modified RECIST, and the Baseline Tumor
Assessment Form [RECIST 1.1] using RECIST 1.1.)
• Participants may have measurable or non-measurable extracranial disease. All
measurable disease must be assessed within 28 days prior to randomization; all
non-measurable disease must be assessed within 42 days prior to randomization. Please
note, while any extracranial disease will also be assessed and followed, participants
are NOT required to have extracranial disease for randomization. NOTE: All disease
must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1).
CNS disease must be documented on BOTH the Brain Metastases Baseline Tumor Assessment
Form, using modified RECIST, and the Baseline Tumor Assessment Form (RECIST 1.1) using
RECIST 1.1
• Participants may have leptomeningeal disease
• Participants may be receiving corticosteroids for brain metastases at a dose of up to
8 mg of dexamethasone per day. The dose must not have exceeded 8 mg per day for at
least 7 days prior to randomization
• Participants must have Zubrod performance status =< 2
• Participants must have complete history and physical examination within 28 days prior
to randomization
• Participants must be able to swallow and retain pills
• Hemoglobin >= 8.0 g/dL (within 28 days prior to randomization)
• Absolute neutrophil count >= 1,500/mcL (within 28 days prior to randomization)
• Platelets >= 75,000/mcL (within 28 days prior to randomization)
• Total bilirubin =< 1.5 institutional upper limit of normal (ULN) (within 28 days prior
to randomization)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x
institutional ULN (in participants with liver metastases =< 5 x ULN) (within 28 days
prior to randomization)
• Creatinine =< 2.0 institutional ULN (within 28 days prior to randomization)
• Participants with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, participants must be class 2B or better
• Participants with a prior or concurrent malignancy whose natural history or treatment
(in the opinion of the treating physician) does not have the potential to interfere
with the safety or efficacy assessment of the investigational regimen are eligible for
this trial
• Participants with known human immunodeficiency virus (HIV)-infection are eligible
providing they are on effective anti-retroviral therapy and have undetectable viral
load at their most recent viral load test and within 90 days prior to randomization
• Participants with a known history of hepatitis C virus (HCV) infection must have been
treated and cured. Participants with HCV infection who are currently on treatment must
have an undetectable HCV viral load prior to randomization
• Participants must agree to participate in image banking. Images must be submitted via
the Triad System
• Participants must be offered the opportunity to participate in specimen and blood
collections
• Participants must be informed of the investigational nature of this study and must
sign and give informed consent in accordance with institutional and federal guidelines
• As a part of the OPEN registration process the treating institution's identity is
provided in order to ensure that the current (within 365 days) date of institutional
review board approval for this study has been entered in the system
Exclusion Criteria:
• Participants must not have received prior systemic therapy for metastatic disease.
Prior systemic therapy received only in the neoadjuvant and/or adjuvant setting (e.g.,
BRAF/MEK inhibitor therapy, anti-PD-1 therapy or anti-CTLA4 therapy, alfa-interferon,
etc.) is permitted. If patients received prior neoadjuvant/adjuvant therapy, they must
have had eventual disease relapse prior to randomization
• Participants must not have had prior radiation therapy within 7 days prior to
randomization
• Participants must not be planning to require any additional form of systemic
anti-tumor therapy for melanoma while on protocol treatment
• Participants must not be planning to use hormonal contraceptives
• Participants must not have a serious active infection requiring systemic therapy at
time of randomization in the opinion of the treating physician
• Participants must not have active autoimmune disease that has required treatment in
the past 6 months with use of biologic disease modifying agents (.e.g. infliximab,
adalimumab). Patients on non-biologic disease modifying agents (e.g. methotrexate) or
patients on corticosteroids =< 10 mg prednisone daily or equivalent (to treat
auto-immune disease), or on replacement therapy (e.g., thyroxine, insulin) are
eligible if deemed in the best interest of the patient by treating physician
• Participants must not have had grade 3 or 4 immune-related adverse events on
ipilimumab or nivolumab that required more than 12 weeks of immune suppression with
corticosteroids
• Participants must not have had adverse events related to encorafenib and/or
binimetinib specifically, that required discontinuation of one or both drugs. (Please
note this does not apply to other BRAF/MEK inhibitor drugs.)
• Participants must not be pregnant or nursing. Women/men of reproductive potential must
have agreed to use an effective method of contraception. (NOTE: Patients must agree to
not use hormonal contraceptives, as encorafenib can result in decreased concentration
and loss of efficacy.) A woman is considered to be of "reproductive potential" if she
has had menses at any time in the preceding 12 consecutive months. In addition to
routine contraceptive methods, "effective contraception" also includes heterosexual
celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy
prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal
ligation. However, if at any point a previously celibate participant chooses to become
heterosexually active during the time period for use of contraceptive measures
outlined in the protocol, he/she is responsible for beginning contraceptive measures
Acral Lentiginous Melanoma, Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Cutaneous Melanoma, Metastatic Malignant Neoplasm in the Brain, Metastatic Melanoma, Metastatic Mucosal Melanoma, Pathologic Stage IV Cutaneous Melanoma AJCC v8, Melanoma, Skin, Melanoma/Skin cancer
Safety and Efficacy of ALXN1720 in Adults With Generalized Myasthenia Gravis
The purpose of this study is to evaluate the safety and efficacy of ALXN1720 for the
treatment of generalized MG (gMG) in adults with autoantibodies against acetylcholine
receptor (AChR).
Stephanie Gardon
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05556096
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Inclusion Criteria:
• Diagnosis of MG with generalized muscle weakness meeting the clinical criteria defined
by Myasthenia Gravis Foundation of America (MGFA) Class II, III or IV
• Positive serological test for autoantibodies against AChR
Exclusion Criteria:
• History of thymectomy, or any other thymic surgery within 12 months prior to Screening
• Untreated thymic malignancy, carcinoma, or thymoma
• History of Neisseria meningitidis infection
• Pregnancy, breastfeeding, or intention to conceive during the course of the study
Generalized Myasthenia Gravis, Myasthenia gravis and other myoneural disorders, Other, Brain & Neurological
A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT
This phase II trial studies the best approach to combine chemotherapy and radiation therapy
(RT) based on the patient's response to induction chemotherapy in patients with
non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain
or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond
well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose
chemotherapy followed by conventional RT in patients who did not respond to induction
chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa,
work in different ways to stop the growth of tumor cells, either by killing the cells, by
stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high
energy x-rays or high-energy protons to kill tumor cells and shrink tumors. Studies have
shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to
chemotherapy before receiving radiation therapy, are more likely to be free of the disease
for a longer time than are patients for whom the chemotherapy does not efficiently eliminate
or reduce the size of the tumor. The purpose of this study is to see how well the tumors
respond to induction chemotherapy to decide what treatment to give next. Some patients will
be given RT to the spine and a portion of the brain. Others will be given high dose
chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving
treatment based on the response to induction chemotherapy may lower the side effects of
radiation in some patients and adjust the therapy to a more efficient one for other patients
with localized NGGCT.
Kenneth Desantes, M.D.
All
3 Years to 29 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04684368
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Inclusion Criteria:
• Patients must be >= 3 years and < 30 years at the time of study enrollment
• Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar
and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation
of AFP above institutional normal or > 10 ng/mL or human chorionic gonadotropin (hCG)
beta > 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on
APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers
and cytology must be within 31 days prior to enrollment and start of protocol therapy
[repeat if necessary]. Serum tumor markers, AFP and hCGbeta must be within 7 days
prior to enrollment and start of protocol therapy [repeat if necessary]). Basal
ganglia or other primary sites are excluded
• Patients with any of the following pathological elements are eligible: endodermal
sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma
and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant
elements listed above are present. Patients with only mature teratoma are excluded.
Patients with pure germinoma admixed with mature teratoma are excluded (would be
eligible for pure germinoma protocols)
• Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to
enrollment. If surgical resection is performed, patients must have pre-operative and
post operative brain MRI with and without gadolinium. The post operative brain MRI
should be obtained within 72 hours of surgery. If patient has a biopsy only,
post-operative brain MRI is recommended but not required (within 31 days prior to
study enrollment and start of protocol therapy )
• Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to
enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior
to study enrollment and start of protocol therapy)
• Lumbar CSF must be obtained prior to study enrollment unless medically
contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be
obtained at the time of surgery, then it should be performed at least 10 days
following surgery and prior to study enrollment. False positive cytology can occur
within 10 days of surgery
• Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained prior
to enrollment unless medically contraindicated. Ventricular CSF obtained at the time
of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar
CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor
markers should be collected first
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to
enrollment)
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to
enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days
prior to enrollment)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 7 days
prior to enrollment):
• Age: Maximum serum creatinine (mg/dL)
• 3 to < 6 years: 0.8 (male), 0.8 (female)
• 6 to < 10 years: 1 (male), 1 (female)
• 10 to < 13 years: 1.2 (male), 1.2 (female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: male (1.7), 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L (within 7 days prior to enrollment)
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L
• Central nervous system function defined as:
• Patients with seizure disorder may be enrolled if on anticonvulsants and well
controlled
• Patients must not be in status epilepticus, coma or assisted ventilation prior to
study enrollment
• Protocol therapy must begin within 31 calendar days of definitive surgery or clinical
diagnosis, whichever is later. If a biopsy only was performed, the biopsy date will be
considered the date of definitive surgery. For patients who have a biopsy or
incomplete resection at diagnosis followed by additional surgery, the date of the last
resection will be considered the date of definitive surgery.
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
• NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:
• English-, Spanish-, or French- speaking
• Note: Patients who speak a language other than English, Spanish, or French will
be allowed to participate in ACNS2021 but will not complete the neurocognitive
and quality of life assessments
• No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g.,
Down syndrome, fragile X, William syndrome, intellectual disability). Patients with
NF1 will be allowed to participate
• Additional eligibility criteria for the COG Standardized Neuropsychological Battery
only: must be at a site that has a psychologist to administer the battery
• Note: If not eligible for the COG Standardized Battery, patients should still
complete the Behavior Rating Inventory of Executive Function, Second Edition
(BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior
Assessment System Third Edition (ABAS-3), and Behavior Assessment System for
Children, Third Edition (BASC-3) questionnaires
Exclusion Criteria:
• Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)
• Patients with only mature teratoma and non-elevated markers upon tumor sampling at
diagnosis
• Patients who have received any prior tumor-directed therapy for their diagnosis of
NGGCT other than surgical intervention and corticosteroids
• Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or
intraoperative evidence of dissemination)
• Female patients who are pregnant, since fetal toxicities and teratogenic effects have
been noted for several of the study drugs
• Note: Serum and urine pregnancy tests may be falsely positive due to
HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by
institutional standards
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
Central Nervous System Nongerminomatous Germ Cell Tumor, Choriocarcinoma, Embryonal Carcinoma, Immature Teratoma, Malignant Teratoma, Mixed Germ Cell Tumor, Pineal Region Germ Cell Tumor, Pineal Region Immature Teratoma, Pineal Region Yolk Sac Tumor, Suprasellar Germ Cell Tumor, Brain and Nervous System, Brain/Central Nervous System
This study will evaluate the effectiveness and safety of an investigational product (IP),
intravenous (IV) ganaxolone, to treat participants with status epilepticus (SE).
Aaron Struck, Medical Student
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04391569
Show full eligibility criteria
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Inclusion Criteria:
1. Participant, participant's parent, guardian, or legal authorized representative (LAR)
must provide signed of informed consent/assent, and once capable (per institution
guidelines), there must be documentation of consent/assent by the participant
demonstrating they are willing and aware of the investigational nature of the study
and related procedures. Where allowed by law, where the participant lacks the capacity
to make informed decisions regarding his/her medical treatment options, the treating
clinician may follow their deferred consenting practices. The clinician will make the
final decision based on the best interests of the particiapant.
2. Male or females 12 years of age and older at the time of the first dose of IP
3. SE meeting the following criteria:
a. A diagnosis of SE with or without prominent motor features based on clinical and
EEG findings:
i. Diagnosis is established by:
• For SE with prominent motor features: Clinical and EEG seizure activity
indicative of convulsive, myoclonic or focal motor SE.
• For SE without prominent motor features (nonconvulsive SE): Appropriate clinical
features and an EEG indicative of non-convulsive status epilepticus (NCSE)
ii. For any type of SE:
• At least 6 minutes of cumulative seizure activity over a 30-minute period within
the hour before IP initiation, AND
• Seizure activity during the 30 minutes immediately prior to IP initiation
b. The treating clinician(s) anticipate that IV anesthesia is likely to be the
next treatment for SE that persists following initiation of IP
4. Participants must have received any two or more of the following agents for treatment
of the current episode of SE administered at an adequate dose and for a sufficient
duration, in the judgment of the investigator, to demonstrate efficacy
• Benzodiazepines,
• IV Fosphenytoin/phenytoin,
• IV Valproic acid,
• IV Levetiracetam,
• IV Lacosamide,
• IV Brivaracetam, or
• IV Phenobarbital
5. Body mass index (BMI) < 40 or, if BMI is not able to be calculated at screening,
participant is assessed by investigator as not morbidly obese
Exclusion Criteria:
1. Life expectancy of less than 24 hours
2. Anoxic brain injury or an uncorrected rapidly reversable metabolic condition as the
primary cause of SE (e.g., hypoglycemia < 50 milligram per deciliter [mg/dL] or
hyperglycemia > 400 mg/dL)
3. Participants who have received high-dose IV anesthetics (e.g., midazolam, propofol,
thiopental, or pentobarbital) during the current episode of SE for more than 18 hours,
or who continue to have clinical or electrographic evidence of persistent seizures
while receiving high-dose IV anesthetics.
4. Clinical condition or advance directive that would NOT permit use of IV anesthesia
5. Participants known or suspected to be pregnant
6. Participants with known allergy or sensitivity to progesterone or allopregnanolone
medications/supplements
7. Receiving a concomitant IV product containing Captisol®
8. Known or suspected hepatic insufficiency or hepatic failure leading to impaired
synthetic liver function.
9. Known or suspected stage 3B (moderate to severe; estimated glomerular filtration rate
[eGFR] 44-30 milliliter/minutes/1.73-meter square [mL/min/1.73m^2]), stage 4 (severe;
eGFR 29-15 mL/min/1.73m^2), or stage 5 (kidney failure; eGFR < 15 mL/min/1.73m^2 or
dialysis) kidney disease
10. Use of an investigational product for which less than 30 days or 5 half-lives have
elapsed from the final product administration. Participation in a non-interventional
clinical study does not exclude eligibility.
Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA)
The primary goal of the trial is to determine if the experimental arms (rivaroxaban or
ticagrelor or both) are superior to the clopidogrel arm for lowering the 1-year rate of
ischemic stroke, intracerebral hemorrhage, or vascular death.
Azam Ahmed, MD
All
30 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05047172
Show full eligibility criteria
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Inclusion Criteria:
• Acute focal symptoms or signs of any duration associated with imaging, pathological,
or other objective evidence of arterial infarction OR clinical evidence of cerebral,
spinal cord, or retinal focal arterial ischemic injury based on symptoms persisting
greater than or equal to 24 hours that occurred within 30 days prior to randomization
• Index stroke is attributed to 70-99% stenosis (or flow gap on MRA) of a major
intracranial artery (carotid artery, middle cerebral artery (M1 or M2), vertebral
artery (V4), basilar artery, posterior cerebral artery (P1), or anterior cerebral
artery (A1)) documented by CTA, MRA, or catheter angiography
• Modified Rankin Scale score of ≤ 4, at time of consent
• Ability to swallow pills
• At least 30 years of age, inclusive, at time of consent
• Subjects 30-49 years of age are required to meet at least ONE of the following
additional criteria below to qualify for the study:
1. diabetes treated with insulin for at least 15 years
2. at least 2 of the following atherosclerotic risk factors: hypertension (BP >
140/90 or on antihypertensive therapy); dyslipidemia (LDL > 130 mg /dl or HDL <
40 mg/dl or fasting triglycerides > 150 mg/dl or on lipid lowering therapy);
smoking; non-insulin dependent diabetes or insulin dependent diabetes of less
than 15 years duration; any of the following vascular events occurring in a
parent or sibling who was < 55 years of age for men or < 65 years of age for
women at the time of the event: myocardial infarction, coronary artery bypass,
coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting,
peripheral vascular surgery for atherosclerotic disease
3. personal history of any of the following: myocardial infarction, coronary artery
bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or
peripheral vascular surgery for atherosclerotic disease
4. any stenosis of an extracranial carotid or vertebral artery, another intracranial
artery, subclavian artery, coronary artery, iliac or femoral artery, other lower
or upper extremity artery, mesenteric artery, or renal artery that was documented
by non-invasive vascular imaging or catheter angiography and is considered
atherosclerotic
5. aortic arch atheroma documented by non-invasive vascular imaging or catheter
angiography
6. any aortic aneurysm documented by non-invasive vascular imaging or catheter
angiography that is considered atherosclerotic
• Negative pregnancy test in a female who has had any menses in the last 18 months and
has not had surgery that would make her unable to become pregnant
• Subject is willing and able to return for all follow-up evaluations required by the
protocol
• Subject is available by phone
• Subject understands the purpose and requirements of the study and can make him/herself
understood
• Subject has provided informed consent (use of a LAR is not permitted)
Exclusion Criteria:
• Previous treatment of target lesion with a stent, angioplasty, or other mechanical
device, including mechanical thrombectomy for the qualifying stroke, or plan to
perform one of these procedures
• Plan to perform concomitant endarterectomy, angioplasty or stenting of an extracranial
vessel tandem to the symptomatic intracranial stenosis
• Intracranial tumor (except meningioma) or any intracranial vascular malformation
• Thrombolytic therapy within 24 hours prior to randomization
• Progressive neurological signs within 24 hours prior to randomization
• History of any intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural)
• Intracranial arterial stenosis due to: arterial dissection; MoyaMoya disease; any
known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy;
neurosyphilis; any other intracranial infection; any intracranial stenosis associated
with CSF pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle
cell disease; neurofibromatosis; benign angiopathy of central nervous system;
postpartum angiopathy; suspected vasospastic process; reversible cerebral
vasoconstriction syndrome (RCVS); suspected recanalized embolus
• Presence of any of the following unequivocal cardiac sources of embolism: chronic or
paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis,
intracardiac clot or vegetation, myocardial infarction within three months, left
atrial spontaneous echo contrast
• Known allergy or contraindication to aspirin, rivaroxaban, clopidogrel, or ticagrelor
• Uncontrolled severe hypertension (systolic pressure > 180 mm Hg or diastolic pressure
> 115 mm Hg), active peptic ulcer disease, major systemic hemorrhage within 30 days
prior to randomization, active bleed or bleeding diathesis, platelets < 100,000,
hematocrit < 30, INR > 1.5, clotting factor abnormality that increases the risk of
bleeding, current alcohol or substance abuse, severe liver impairment (AST or ALT > 3
x normal, cirrhosis), or CrCl < 15 mL/min or on dialysis
• Major surgery (including stenting of any vessel; open femoral, aortic, or carotid
surgery; or cardiac surgery) within previous 30 days prior to randomization or planned
in the next 90 days after randomization
• Any condition other than intracranial arterial stenosis that requires the subject to
take any antithrombotic medication other than aspirin (NOTE: exceptions allowed for
subcutaneous heparin for deep vein thrombosis (DVT) prophylaxis)
• Dementia or psychiatric problem that prevents the subject from following an outpatient
program reliably
• Co-morbid conditions that may limit survival to less than 12 months
• Pregnancy or of childbearing potential and unwilling to use contraception for the
duration of this study, or currently breastfeeding
• Current or anticipated concomitant oral or intravenous therapy with strong CYP3A4
inhibitors or CYP3A4 substrates that cannot be stopped for the course of this study
• Enrollment in another study that would conflict with the current study
This Study Aims to Find the Best Dose of BI 907828 (Brigimadlin) in Patients With Different Types of Advanced Cancer (Solid Tumors)
This study is open to adults with different types of advanced cancer (solid tumors). The
purpose of this study is to find out the most suitable dose of BI 907828 (brigimadlin) the
participants can tolerate. The most suitable dose is used in the second part to find out
whether brigimadlin makes tumors shrink.
In this study, brigimadlin is given to humans for the first time. Brigimadlin is a so-called
MDM2 inhibitor that is being developed to treat cancer. Brigimadlin is taken as a tablet.
Participants either take a dose of brigimadlin on one day every 3 weeks or on two days every
4 weeks.
The participants are in the study for as long as they benefit from and can tolerate
treatment. The doctors regularly check the participants' general health during the study.
Jeremy Kratz, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT03449381
Show full eligibility criteria
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Inclusion Criteria:
• Provision of signed and dated, written informed consent form ICF in accordance with
ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or
analyses.
• Pathologically documented, advanced solid tumors.
• Patients fulfilling one or more of the following criteria:
• Radiologically documented disease progression or relapse
• Patients who are not eligible to receive standard of care treatments, and for
whom no proven treatments exist.
• Patients with MDM2 amplified sarcomas who require first line treatment (for Ph
Ib/dose expansion •Cohort 1 only).
• Patients with MDM2 amplified sarcomas may fulfil any one of the above three criteria
to be considered eligible.
• Phase Ia (dose escalation) only:
• Patient has a tumor with either a known TP53 wild type status, or unknown TP53 status,
and regardless of MDM2 amplification status, at the time of study entry.
• Phase Ib (expansion phase) only:
• Cohort 1: TP53 wt and MDM2-amplified sarcoma with advanced/metastatic disease at any
line of therapy. If TP53 status is not available during screening, the patient may be
included with unknown TP53 status if a tissue sample is submitted for central
laboratory assessment. If TP53 status cannot be evaluated, the patient may be included
if agreed between the Investigator and Sponsor.
• Cohort 2: TP53 wt and MDM2- amplified NSCLC, urothelial, gastric, biliary tract
(including cholangiocarcinoma, intra- and extrahepatic biliary tree, gall blander and
ampulla of vater) or pancreatic solidPDAC tumors who have had at least one previous
line of therapy for advanced/metastatic disease. If TP53 status cannot be evaluated
the patient may be included if agreed between the Investigator and Sponsor
• Phase Ia (dose escalation) only:
• Patient with either measurable or non-measurable disease.
• Non-evaluable disease allowed.
• Phase Ib (expansion phase) only:
• At least one target lesion that can be accurately measured per RECIST v.1.1.
• Phase Ia:
• Patient must be willing to undergo blood sampling for PK, pharmacodynamic, biomarker,
and PGx analyses.
• Phase Ib:
• Patient must be willing to undergo tumor biopsy sampling for pharmacodynamic analyses
and blood sampling for PK, pharmacodynamics, and biomarker analyses.
• Willingness to provide a fresh tumor tissue sample obtained after relapse/ progression
during or after prior therapy. In case a fresh biopsy cannot be obtained (e.g.
inaccessible lesions or patient safety concern), an archived specimen, collected
before screening within 12 months of enrollment, may be submitted. If these
requirements cannot be met, then the patient may be allowed to enter the study at
Sponsor discretion, after agreement between the Investigator and Sponsor.
• Further inclusion criteria apply
Exclusion Criteria:
• Previous administration of BI 907828 (brigimadlin) or any other MDM2-p53 or MDMX
(MDM4)-p53 antagonist.
• Known TP53 mutant tumor.
• Symptomatic metastases from non-brain tumors. Note: Patients with previously treated
brain metastases may participate provided they are stable, without evidence of
progression by imaging (using the identical imaging modality for each assessment,
either MRI or computed tomography (CT) scan), for at least four weeks prior to the
first dose of trial treatment, and any neurologic symptoms have returned to baseline;
have no evidence of new or enlarging brain metastases. Patients on corticosteroids
must have a stable dose for at least 5 days prior to baseline MRI.
• Patients with history of bleeding diathesis.
• Major surgery (major according to the Investigator's assessment) performed within 12
weeks prior to start of study treatment, or planned within 12 months after screening
(e.g. hip replacement).
• Any other documented active or suspected malignancy or history of malignancy within 3
years prior to screening, except appropriately treated basal cell carcinoma of the
skin or in situ carcinoma of uterine cervix, or other local tumors considered cured by
local treatment.
• Patients who must or wish to continue the intake of restricted medications or any drug
considered likely to interfere with the safe conduct of the trial.
• Further exclusion criteria apply.
Neoplasms, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene
This phase I trial tests the safety, side effects, and best dose of neratinib in combination
with trastuzumab deruxtecan in treating patients with solid tumors that have spread to other
parts of the body (metastatic) or that cannot be removed by surgery (unresectable), and have
changes in a gene called human epidermal growth factor receptor 2 (HER2). Neratinib is in a
class of medications called kinase inhibitors. It works by blocking the action of an abnormal
protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor
cells. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates.
It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug,
called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and
delivers deruxtecan to kill them. Adding neratinib to trastuzumab deruxtecan may be able to
shrink cancer with a change in the HER2 gene.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05372614
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Inclusion Criteria:
• Patients must have histologically confirmed malignancy that is metastatic or
unresectable with participation in this clinical trial determined to be the best
option for next treatment in the opinion of the investigator
• Patients must have a solid tumor with HER2-positivity as determined by any one or more
of the following:
• HER2 overexpression defined by IHC 3+
• ERBB2 amplification by ISH or next-generation sequencing as determined by any
CLIA certified lab
• A known HER2 activating mutation
• HER2 overexpression by IHC/ISH will follow histology specific ASCO-CAP guidelines
for breast and gastric cancers. For tumor histologies without specific guidelines
the following criteria will apply:
• HER2 IHC should be performed first, followed by ISH methods in cases showing
2+ (equivocal) expression by IHC. Positive (IHC 3+) or negative (IHC 0 or
1+) do not require further ISH testing. Cases with HER2:CEP17 ratio ≥2 or an
average HER2 copy number ≥6.0 signals per cell are considered positive by
ISH
• Known HER2 activating mutations:
• G309A/E
• S310F/Y
• S653C
• V659E
• G660D
• R678Q
• E693K
• Q709L
• L755S/P
• Del. 755-759
• D769Y/H
• G776V/C
• V777L
• V842I
• T862A
• L869R
• H878Y
• All exon 20 insertions, including:
• A771_Y772insYVMA
• A775_G776insYVMA
• Y772_A775dup
• P780_Y781insGSP
• G778_P780dup
• V697L
• T733I
• D769N
• L841V
• L866M
• R896C
• If a different mutation is identified, contact the study chair for conferral.
Synonymous mutations are not eligible
• Patients must have received at least 1 prior line of therapy in the
advanced/metastatic setting. No limitation on number of prior therapies; however,
patients may not have received neratinib or DS-8201a previously. Prior HER2-targeted
therapy other than neratinib or DS-8201a is allowed (e.g., trastuzumab, pertuzumab,
TDM-1, lapatinib, etc.)
• Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of neratinib in combination with DS-8201a in patients < 18 years of age,
children are excluded from this study
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
(Karnofsky >= 70%)
• Hemoglobin >= 9.0 g/dL (>= 8.0 g/dL for gastric cancer [GC] only) (within 14 days of
enrollment)
• No transfusions with red blood cells or platelets are allowed within 1 week prior
to screening assessment
• Serum albumin >= 2.5 g/dL (within 14 days of enrollment)
• Leukocytes >= 3.0 K/cumm (within 14 days of enrollment)
• Absolute neutrophil count >= 1.5 K/cumm (within 14 days of enrollment)
• No administration of granulocyte colony-stimulating factor (G-CSF) is allowed
within 1 week prior to screening assessment
• Platelets >= 100 K/cumm (within 14 days of enrollment)
• No transfusions with red blood cells or platelets are allowed within 1 week prior
to screening assessment
• Total bilirubin =< 1.5 × institutional upper limit of normal (ULN), (< 3 × ULN in the
presence of documented Gilbert's syndrome or liver metastases at baseline) (within 14
days of enrollment)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 x ULN (if liver metastases are present =< 5 x ULN) (within 14 days of enrollment)
• International normalized ratio (INR)/prothrombin time (PT) and activated partial
thromboplastin time (aPTT) =< 1.5 x institutional ULN (within 14 days of enrollment)
• This applies only to patients who are not receiving therapeutic anticoagulation
that may affect INR. Those who are on therapeutic anticoagulation, should be on a
stable dose for 4 weeks and should be considered within therapeutic range
• Creatinine =< 1.5 x institutional ULN OR Glomerular filtration rate (GFR) >= 30
mL/min/1.73 m^2 (using the Cockcroft-Gault equation) (within 14 days of enrollment)
• Patients who are human immunodeficiency virus (HIV)-positive may participate IF they
meet the following eligibility requirements:
• They must be stable on their anti-retroviral regimen, and they must be healthy
from an HIV perspective
• They must have a CD4 count of greater than 250 cells/mcL over the past 6 months
on this same anti-retroviral regimen and must not have had a CD4 count < 200
cells/ul over the past 2 years, unless it was deemed related to THE CANCER AND/OR
CHEMOTHERAPY-induced bone marrow suppression
• For patients who have received chemotherapy in the past 6 months, a CD4
count < 250 cells/ul during chemotherapy is permitted as long as viral loads
were undetectable during this same chemotherapy
• They must have an undetectable viral load and a CD4 count >= 250 cells/uL within
7 days of enrollment
• They must not be currently receiving prophylactic therapy for an opportunistic
infection and must not have had an opportunistic infection within the past 6
months HIV-infected patients should be monitored every 12 weeks for viral load
and CD4 counts
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if the following criteria are met:
1) follow-up brain imaging done at least in 4 weeks after central nervous system
(CNS)-directed therapy shows no evidence of progression and 2) the patient no longer
requires steroids, or is on a stable steroid dose > 4 weeks
• Patients with radiographically new or progressive brain metastases (active brain
metastases) or leptomeningeal disease are eligible only if has no progressive clinical
symptoms and if the treating physician determines that immediate CNS specific
treatment is not required and is unlikely to be required during the first cycle of
therapy
• Patients should be New York Heart Association functional classification of class 2B or
better
• Patients must have left ventricular ejection fraction (LVEF) >= 50% by either an
echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before
randomization/enrollment
• Dose expansion phase (PD cohort): Patients must have disease that is evaluable or
measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Dose expansion phase (PD cohort): Patients must have at least one lesion suitable for
biopsy without significant risk to the patient. The biopsiable lesion can be the same
as the evaluable lesion for response by RECIST 1.1
• Patients who had clinically significant side effects from prior cancer therapy must
have recovered to grade 1 or below
• HER2 antibody conjugated to a topoisomerase 1 inhibitor agents as well as other
therapeutic agents used in this trial are known to be teratogenic; thus, women of
child-bearing potential and men must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry, for the duration of
study participation, and for at least 1 month after the last dose of neratinib, or at
least 7 months after the last dose of DS-8201a, whichever is longer (women of
childbearing potential [WOCBP] only). Should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she should inform
her treating physician immediately. Men treated or enrolled on this protocol must also
agree to use adequate contraception prior to the study, for the duration of study
participation, and 3 months after the last dose of neratinib, or 4 months after
completion of DS-8021a administration, whichever is longer
• Women of non-child-bearing potential defined as pre-menopausal females with a
documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of
spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous
follicle-stimulating hormone [FSH] > 40 mIU/mL and estradiol < 40 pg/mL [< 147 pmol/L]
is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose
menopausal status is in doubt will be required to use one of the contraception methods
outlined for women of child-bearing potential if they wish to continue their HRT
during the study. Otherwise, they must discontinue HRT to allow confirmation of
post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4
weeks will elapse between the cessation of therapy and the blood draw; this interval
depends on the type and dosage of HRT. Following confirmation of their post-menopausal
status, they can resume use of HRT during the study without use of a contraceptive
method
• Male subjects must not freeze or donate sperm starting at screening and throughout the
study period, and at least 4 months after the final study drug administration.
Preservation of sperm should be considered prior to enrollment in this study
• Female subjects must not donate, or retrieve for their own use, ova from the time of
screening and throughout the study treatment period, and for at least 7 months after
the final study drug administration
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity who have a legally-authorized
representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
• With the exception of medications that are under investigation in the study (e.g.,
standard of care, comparators, or combination therapies), the following medications,
treatment, and procedures will be prohibited during the treatment period. The sponsor
must be notified if a subject receives any of these during the study:
• Other anticancer therapy, including small-molecule targeted agents within 2 weeks
or five half-lives, whichever is longer; chemotherapy otherwise not specified
(including, but not limited to cytotoxic chemotherapy, antibody drug conjugates,
retinoid therapy, hormonal therapy) within 3 weeks; immunotherapy or monoclonal
antibody within 4 weeks; and nitrosureas or mitomycin C within 6 weeks
(concurrent use of hormones for noncancer-related conditions [e.g., insulin for
diabetes and hormone replacement therapy] is acceptable)
• Other investigational therapeutic agents
• Patients who have had major surgery or radiation within 4 weeks; palliative
stereotactic radiation within 2 weeks (except for palliative radiation to known
metastatic sites as long as it does not affect assessment of response or
interrupt treatment for more than the maximum time specified in dose modification
section)
• Radiotherapy to the thorax (palliative radiation to known metastatic sites in the
thoracic spine is permitted in this study)
• Concomitant use of chronic systemic (IV or oral) corticosteroids or other
immunosuppressive medications except for managing adverse events (inhaled
steroids or intra-articular steroid injections are permitted in this study);
chronic replacement dose steroids (e.g., for those with adrenal insufficiency)
are permitted in this study
• Subjects with bronchopulmonary disorders who require intermittent use of
bronchodilators (such as albuterol) will not be excluded from this study
• Concomitant treatment with chloroquine or hydroxychloroquine is not allowed
during the study treatment due to concern for overlapping toxicities. If
treatment with chloroquine and hydroxychloroquine treatment is absolutely
required, study treatment must be interrupted. If chloroquine or
hydroxychloroquine is administered, then a wash-out period of more than 14 days
is required before restarting study treatment
• Patients with a history of (non-infectious) interstitial lung disease
(ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where
suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Patients with clinically severe pulmonary compromise resulting from intercurrent
pulmonary illnesses including, but not limited to, any underlying pulmonary disorder
(i.e. pulmonary emboli within three months of the study enrollment, severe asthma,
severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural
effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with
potential pulmonary involvement (i.e. rheumatoid arthritis, Sjogren's, sarcoidosis,
etc.), or prior pneumonectomy
• Patients with history of allergic reactions attributed to compounds of similar
chemical or biologic composition to DS-8201a, the inactive ingredients in the drug
product, or neratinib
• Patients who have a history of severe hypersensitivity reactions to other monoclonal
antibodies
• Patients receiving any medications or substances that are moderate or strong
inhibitors or inducers of CYP3A4 and P-glycoprotein are ineligible. Avoid concomitant
use with proton pump inhibitors and P-glycoprotein substrates. Because the lists of
these agents are constantly changing, it is important to regularly consult a
frequently-updated medical reference. As part of the enrollment/informed consent
procedures, the patient will be counseled on the risk of interactions with other
agents, and what to do if new medications need to be prescribed or if the patient is
considering a new over-the-counter medicine or herbal product
• Patients with a medical history of myocardial infarction within 6 months before
enrollment, or symptomatic congestive heart failure (CHF) (New York Heart Association
class II to IV)
• Patients with a corrected QT interval (QTc) prolongation to > 470 ms (females) or >
450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram
(ECG)
• Patients with clinically significant corneal disease in the opinion of the
investigator
• Patients with a pleural effusion, ascites, or pericardial effusion that requires
drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy
(CART). (Drainage and CART are not allowed within 2 weeks prior to screening
assessment) (GC indication)
• Patients with spinal cord compression
• Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or
antifungals
• Patients with unresolved toxicities from previous anticancer therapy, defined as
toxicities (other than alopecia) not yet resolved to grade =< 1 or baseline. Subjects
with chronic grade 2 toxicities may be eligible per the discretion of the investigator
after consultation with the sponsor medical monitor or designee (e.g., grade 2
chemotherapy-induced neuropathy)
• Patients with substance abuse or any other medical conditions such as clinically
significant cardiac or psychological conditions, that may, in the opinion of the
investigator, interfere with the subject's participation in the clinical study or
evaluation of the clinical study results
• Pregnant women are excluded from this study because DS-8201a is a HER2 antibody
conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or
abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with DS-8201a,
breastfeeding should be discontinued if the mother is treated with DS-8201a. These
potential risks may also apply to other agents used in this study
• Prior treatment with neratinib or DS-8201a
• Clinically significant chronic gastrointestinal disorder with diarrhea as a major
symptom; G2 or greater diarrhea at baseline. Please contact the study PI for any
patient with more than two episodes of diarrhea per day averaged over at least a 7 day
period at time of screening to determine whether the diarrhea would be considered
clinically significant
• Inability to swallow tablets
• Patients with active additional malignancy or a personal history of additional
malignancy that may affect outcome of disease under treatment (patients with a prior
or concurrent malignancy whose natural history or treatment does not have the
potential to interfere with the safety or efficacy assessment of the investigational
regimen at the discretion of the treating investigator are allowed)
• Patients with prior allogeneic organ transplantation including allogeneic stem cell
transplantation
Malignant Solid Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
This study collects blood and tissue samples from patients with cancer and without cancer to
evaluate tests for early cancer detection. Collecting and storing samples of blood and tissue
from patients with and without cancer to study in the laboratory may help researchers develop
tests for the early detection of cancers.
David Kosoff, MD
All
40 Years to 75 Years old
N/A
This study is also accepting healthy volunteers
NCT05334069
Show full eligibility criteria
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Inclusion Criteria:
• Participants with a cancer diagnosis: Documentation of disease:
• Histologic documentation: Histologically confirmed diagnosis of invasive cancer
• Stage: Stage I-IV per American Joint Committee on Cancer (AJCC) 7th edition, with
the exception of patients with leukemia, lymphoma, and multiple myeloma
• For leukemia: Type (chronic lymphocytic leukemia [CLL], chronic myeloid
leukemia [CML], acute lymphoblastic lymphoma [ALL], acute myeloid leukemia
[AML])
• For lymphoma: Stage I-IV based on Ann Arbor staging
• For multiple myeloma: Stage I, II, III based on Revised International
Staging System (RISS)
• One of the following tumor types:
• Colorectal
• Bladder
• Head and neck
• Hepatobiliary
• Lung
• Lymphoma
• Leukemia
• Ovary *** For these specific cancer types only, patients may be enrolled
prior to histologic confirmation of malignancy. Sites are required to
contact the study chairs to review appropriateness for enrollment
• Pancreas *** For these specific cancer types only, patients may be enrolled
prior to histologic confirmation of malignancy. Sites are required to
contact the study chairs to review appropriateness for enrollment
• Multiple myeloma
• Gastric, esophageal or gastroesophageal
• Breast
• Thyroid
• Kidney
• For these specific cancer types only, patients may be enrolled prior to
histologic confirmation of malignancy. Sites are required to contact
the study chairs to review appropriateness for enrollment
• Endometrium
• Prostate
• Melanoma
*** For these specific cancer types only, patients may be enrolled prior to
histologic confirmation of malignancy. Sites are required to contact the
study chairs to review appropriateness for enrollment
• Sarcoma
• Participants with a cancer diagnosis: No prior definitive systemic or local
anti-cancer intervention
• Participants with a cancer diagnosis: Age >= 40 and =< 75
• Participants with a cancer diagnosis: No known current pregnancy by self-report
• Participants with a cancer diagnosis: No known or prior history of in situ or invasive
malignancy (excluding in situ non-melanoma skin cancers) other than the current cancer
diagnosis
• Participants with a cancer diagnosis: Willingness to provide blood samples for
research use
• Participants with a cancer diagnosis: Absence of medical contraindications to a
research blood draw volume of 60 mL
• Participants with a cancer diagnosis: No history of organ transplantation
• Participants with a cancer diagnosis: Ability to read and comprehend English or
Spanish
* Eligibility is restricted to individuals who can comprehend and read English or
Spanish given that participation in the study will require the ability to read and
complete questionnaires that are available only in those two languages
• Participants without a cancer diagnosis and without suspicion of cancer: Age >= 40 and
=< 75
• Participants without a cancer diagnosis and without suspicion of cancer: No known
current pregnancy by self-report
• Participants without a cancer diagnosis and without suspicion of cancer: No known or
prior history of in situ or invasive malignancy (excluding in situ non-melanoma skin
cancers)
• Participants without a cancer diagnosis and without suspicion of cancer: Willingness
to provide blood samples for research use
• Participants without a cancer diagnosis and without suspicion of cancer: Absence of
medical contraindications to a research blood draw volume of 60 mL
• Participants without a cancer diagnosis and without suspicion of cancer: No history of
organ transplantation
• Participants without a cancer diagnosis and without suspicion of cancer: Ability to
read and comprehend English or Spanish
* Eligibility is restricted to individuals who can comprehend and read English or
Spanish given that participation in the study will require the ability to read and
complete questionnaires that are available only in those two languages
• Participants with a high suspicion of cancer: High suspicion of ovarian cancer,
pancreatic cancer, kidney cancer, or melanoma by clinical and/or radiological
assessment, with plans for histologic or cytologic confirmation within 28 days after
study blood draw
* Examples of highly suspicious cases include: elevated CA125 and abnormal
transvaginal ultrasound, suspicious renal or pancreatic mass on imaging, suspicious
cutaneous lesion concerning for melanoma
• Participants with a high suspicion of cancer: Central review of radiology reports
and/or clinical documentation conducted by study chairs
• Participants with a high suspicion of cancer: Age >= 40 and =< 75
• Participants with a high suspicion of cancer: No known current pregnancy by
self-report
• Participants with a high suspicion of cancer: No known or prior history of in situ or
invasive malignancy (excluding in situ non-melanoma skin cancers) other than the
current cancer diagnosis
• Participants with a high suspicion of cancer: Willingness to provide blood samples for
research use
• Participants with a high suspicion of cancer: Absence of medical contraindications to
a research blood draw volume of 60 mL
• Participants with a high suspicion of cancer: No history or organ transplantation
• Participants with a high suspicion of cancer: Ability to read and comprehend English
or Spanish * Eligibility is restricted to individuals who can comprehend and read
English and Spanish given that participation in the study will require the ability to
read and complete questionnaires that are available only in those two languages
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Uterus, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Ann Arbor Stage I Lymphoma, Ann Arbor Stage II Lymphoma, Ann Arbor Stage III Lymphoma, Ann Arbor Stage IV Lymphoma, Chronic Lymphocytic Leukemia, Chronic Myeloid Leukemia, Gastroesophageal Junction Adenocarcinoma, Head and Neck Carcinoma, Hematopoietic and Lymphoid Cell Neoplasm, Invasive Breast Carcinoma, Kidney Carcinoma, Malignant Hepatobiliary Neoplasm, Malignant Solid Neoplasm, Melanoma, Muscle-Invasive Bladder Carcinoma, RISS Stage I Plasma Cell Myeloma, RISS Stage II Plasma Cell Myeloma, RISS Stage III Plasma Cell Myeloma, Sarcoma, Stage I Bladder Cancer AJCC v6 and v7, Stage I Breast Cancer AJCC v7, Stage I Colorectal Cancer AJCC v6 and v7, Stage I Esophageal Cancer AJCC V7, Stage I Gastric Cancer AJCC V7, Stage I Lung Cancer AJCC v7, Stage I Ovarian Cancer AJCC v6 and v7, Stage I Pancreatic Cancer AJCC v6 and v7, Stage I Prostate Cancer AJCC v7, Stage I Uterine Corpus Cancer AJCC v7, Stage II Bladder Cancer AJCC v6 and v7, Stage II Breast Cancer AJCC v6 and v7, Stage II Colorectal Cancer AJCC v7, Stage II Esophageal Cancer AJCC v7, Stage II Gastric Cancer AJCC v7, Stage II Lung Cancer AJCC v7, Stage II Ovarian Cancer AJCC v6 and v7, Stage II Pancreatic Cancer AJCC v6 and v7, Stage II Prostate Cancer AJCC v7, Stage II Uterine Corpus Cancer AJCC v7, Stage III Bladder Cancer AJCC v6 and v7, Stage III Breast Cancer AJCC v7, Stage III Colorectal Cancer AJCC v7, Stage III Esophageal Cancer AJCC v7, Stage III Gastric Cancer AJCC v7, Stage III Lung Cancer AJCC v7, Stage III Ovarian Cancer AJCC v6 and v7, Stage III Pancreatic Cancer AJCC v6 and v7, Stage III Prostate Cancer AJCC v7, Stage III Uterine Corpus Cancer AJCC v7, Stage IV Bladder Cancer AJCC v7, Stage IV Breast Cancer AJCC v6 and v7, Stage IV Colorectal Cancer AJCC v7, Stage IV Esophageal Cancer AJCC v7, Stage IV Gastric Cancer AJCC v7, Stage IV Lung Cancer AJCC v7, Stage IV Ovarian Cancer AJCC v6 and v7, Stage IV Pancreatic Cancer AJCC v6 and v7, Stage IV Prostate Cancer AJCC v7, Stage IV Uterine Corpus Cancer AJCC v7, Thyroid Gland Carcinoma
This is a pediatric basket study to investigate the safety and efficacy of afamitresgene
autoleucel in HLA-A*02 eligible and MAGE-A4 positive subjects aged 2-21 years of age with
advanced cancers
Christian Capitini, MD
All
2 Years to 21 Years old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05642455
Show full eligibility criteria
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Inclusion Criteria:
• Age 2-21 years
• Body weight ≥ 10 kg
• Subject has histologically confirmed diagnosis of any one of the following cancers:
(A) Synovial Sarcoma, (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma
• Must have previously received a systemic chemotherapy
• Measurable disease according to RECIST v1.1 (or INCR, 2017 Neuroblastoma only).
• HLA-A*02 positive
• Tumor shows MAGE-A4 expression confirmed by central laboratory.
• Performance Status: ECOG 0-1 or Lansky Score ≥ 80
Exclusion Criteria:
• HLA-A*02:05 in either allele; or any A*02 having same protein sequence as HLA-A*02:05
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to fludarabine, cyclophosphamide.
• History of autoimmune or immune mediated disease
• Known central nervous system (CNS) metastases.
• Other prior malignancy that is not considered by the Investigator to be in complete
remission
• Clinically significant cardiovascular disease
• Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C
virus, or human T cell leukemia virus
• Pregnant or breastfeeding
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus, Synovial Sarcoma, Malignant Peripheral Nerve Sheath Tumor (MPNST), Neuroblastoma, Osteosarcoma
Comparing the Addition of Radiation Either Before or After Surgery for Patients With Brain Metastases
This phase III trial compares the addition of stereotactic radiosurgery before or after
surgery in treating patients with cancer that has spread to the brain (brain metastases).
Stereotactic radiosurgery is a type of radiation therapy that delivers a high dose of
radiation only to the small areas of cancer in the brain and avoids the surrounding normal
brain tissue. Surgery and radiation may stop the tumor from growing for a few months or
longer and may reduce symptoms of brain metastases.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05438212
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Inclusion Criteria:
• Radiographic confirmation of 1-4 brain metastases, one of which requires resection, as
defined by magnetic resonance imaging (MRI) with contrast obtained within 14 days
prior to registration
• The maximum diameter of the lesion to be resected on the post-contrast MRI, as
measured on any orthogonal plane (axial, sagittal, coronal), must measure > 2.0
cm and < 5.0 cm.
• The maximum diameter of the lesions not to be resected must measure < 4.0 cm
• Known active or history of invasive non-central nervous system (CNS) primary cancer
based on documented pathologic diagnosis within the past 3 years
• All brain metastases must be located > 5 mm from the optic chiasm and outside the
brainstem
• Patient is able to medically tolerate surgery and SRS
• The lesion chosen for surgical therapy must be deemed an appropriate target for safe,
gross total resection by the treating surgeon
• History/physical examination within 14 days prior to registration
• Age >= 18
• Karnofsky performance status (KPS) >= 60 within 14 days prior to registration
• A negative urine or serum pregnancy test (in persons of childbearing potential) within
=< 14 days prior to registration. Childbearing potential is defined as any person who
has experienced menarche and who has not undergone surgical sterilization
(hysterectomy or bilateral oophorectomy) or who is not postmenopausal for at least 12
consecutive months
• Participants who are sexually active must agree to use medically acceptable forms of
contraception during treatment on this study to prevent pregnancy
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information
Exclusion Criteria:
• Prior cranial radiotherapy, including whole brain radiotherapy, or SRS to the
resection site
• Note: The index lesion to be resected cannot have been previously treated with
SRS (i.e. repeat radiosurgery to the same location/lesion is not allowed on this
protocol). Previous SRS to other lesions is allowed
• Evidence of leptomeningeal disease (LMD)
• Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as
positive cerebrospinal fluid (CSF) cytology and/or unequivocal radiologic or
clinical evidence of leptomeningeal involvement. Patients with leptomeningeal
symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be
considered to have LMD even in the absence of positive CSF cytology. In contrast,
an asymptomatic or minimally symptomatic patient with mild or nonspecific
leptomeningeal enhancement (MRI) would not be considered to have LMD. In that
patient, CSF sampling is not required to formally exclude LMD, but can be
performed at the investigator's discretion based on level of clinical suspicion
• Any medical conditions which would make this protocol unreasonably hazardous,
including, but not limited to: contraindications to general endotracheal anesthesia;
intracranial surgery; and stereotactic radiosurgery
• Primary histology of germ cell tumor, small cell carcinoma or lymphoma
• More than one brain metastasis planned for resection
• Inability to undergo MRI with contrast
• Planned administration of cytotoxic chemotherapy or tyrosine/multi-kinase inhibitors
within the 3 days prior to, the day of, or within 3 days after the completion of SRS
• Note: chemotherapy and immunotherapy outside of this window are allowed
Metastatic Malignant Neoplasm in the Brain, Colon, Rectum, Lung, Breast, Prostate, Colon and Rectum
Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical
trials to study cancer treatment directed by genetic testing. Patients with solid tumors that
have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places
in the body (advanced) and have progressed on at least one line of standard systemic therapy
or have no standard treatment that has been shown to prolong overall survival may be
candidates for these trials. Genetic tests look at the unique genetic material (genes) of
patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may
benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed
to match patients to a treatment that may work to control their tumor and may help doctors
plan better treatment for patients with locally advanced or advanced solid tumors.
Nataliya Uboha, MD
All
Not specified
Phase 2
This study is NOT accepting healthy volunteers
NCT05564377
Show full eligibility criteria
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Inclusion Criteria:
• Patient must have measurable disease
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
between 0-2 OR patient must have Lansky performance status of >= 50% or Karnofsky
performance status of >= 50%
• Patient must be deemed potentially eligible for a ComboMATCH Treatment Trial as
assessed by the enrolling provider
• All patients must have sequencing results available from a National Cancer Institute
(NCI) credentialed Designated Laboratory (DL)
• Patients must have locally advanced or advanced histologically documented solid tumors
requiring therapy and meet one of the following criteria:
• Patients must have progressed on at least one line of standard systemic therapy
OR
• Patients whose disease has no standard treatment that has been shown to prolong
overall survival
• Patient must meet one of the following requirements:
• Patients 18 years and older who have tumor amenable to minimal risk image-guided
or direct vision biopsy and must be willing and able to undergo a tumor biopsy to
obtain samples for research if the patient is to enroll in a ComboMATCH treatment
trial OR
• Patients 18 years and older who do not have disease that is biopsiable at minimal
risk to the patient must confirm availability of an archival tumor tissue
specimen for submission for research if the patient enrolls to a ComboMATCH
Treatment Trial. This tumor tissue must meet the following criteria:
• Tissue must have been collected within 12 months prior to registration to
the EAY191 Registration Trial
• Patient must not have had a Response Evaluation Criteria in Solid Tumors
(RECIST) response (complete response [CR] or partial response [PR]) to any
intervening therapy after collection of the tissue
• Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be
available OR
• Patients under 18 years old must confirm availability of an archival tumor tissue
specimen for submission for research if patient enrolls to a ComboMATCH Treatment
Trial. This tumor tissue must meet the following criteria:
• Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be
available
• NOTE: See specific ComboMATCH Treatment Trial protocol for tissue collection and
management instructions. Performance of the mandatory research biopsy or
submission of pre-trial formalin-fixed paraffin-embedded (FFPE) and collection
and submission of the blood specimens for the integrated studies will be
performed under the consent authority of the specific treatment trial protocol to
which the patient is registered. No procedures to collect specimens for research
only are to be performed for patients registered to the EAY191 Registration Trial
only
• NOTE: Each ComboMATCH Treatment Trial contains specific eligibility criteria. If
patient is found to not be eligible for the assigned ComboMATCH Treatment Trial,
indication of ineligibility will trigger re-evaluation and potential assignment to
another Treatment Trial
Advanced Malignant Solid Neoplasm, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Locally Advanced Malignant Solid Neoplasm, Malignant Female Reproductive System Neoplasm, Metastatic HER2-Negative Breast Carcinoma, Metastatic Malignant Solid Neoplasm, Recurrent Endometrial Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Malignant Female Reproductive System Neoplasm, Recurrent Malignant Solid Neoplasm, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma, Unresectable HER2-Negative Breast Carcinoma, Unresectable Malignant Solid Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Study of Chemotherapy Plus Ipatasertib for People With Solid Tumors With AKT Mutations, A ComboMATCH Treatment Trial
This phase II ComboMATCH treatment trial tests the usual treatment of chemotherapy
(paclitaxel) plus ipatasertib in patients with solid tumor cancers that that cannot be
removed by surgery (unresectable), has spread to nearby tissue or lymph nodes (locally
advanced) or from where it first started (primary site) to other places in the body
(metastatic), and has an AKT genetic change. Chemotherapy drugs, such as paclitaxel, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Targeted therapy, such as
Ipatasertib, may stop the growth of tumor cells by blocking some of the enzymes needed for
cell growth. The addition of ipatasertib to paclitaxel in solid tumors with an AKT genetic
change could increase the percentage of tumors that shrink as well as lengthen the time that
the tumors remain stable (without progression). Researchers hope to learn if paclitaxel plus
ipatasertib will shrink this type of cancer or stop its growth.
Nataliya Uboha, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05554380
Show full eligibility criteria
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Inclusion Criteria:
• Patient must have enrolled onto EAY191 and must have been given a treatment assignment
to ComboMATCH to EAY191-S3 based on the presence of an actionable mutation as defined
in EAY191
• GENERAL COMBOMATCH EAY191 REGISTRATION INCLUSION CRITERIA:
• Participants must be enrolled on the ComboMATCH Master Registration Trial EAY191
• Participants must have an activating AKT mutation (a known mutation in AKT1, AKT2, or
AKT3, a single nucleotide variant, insertion, or deletion) as determined by the
ComboMATCH screening assessment
• GENERAL COMBOMATCH EAY191 REGISTRATION EXCLUSION CRITERIA:
• Participants must not have an activating KRAS, NRAS, HRAS, or BRAF mutation (a single
nucleotide variant, insertion, or deletion) as determined by the ComboMATCH screening
assessment
• Participants must have disease that can be safely biopsied and agree to a
pre-treatment biopsy or have archival tissue available from within 12 months prior to
the date of registration on the ComboMATCH Registration Trial (EAY191)
• Participants must have a histologically confirmed non-breast solid malignancy
• Participants must have locally advanced, unresectable, or metastatic disease in the
opinion of the treating investigator
• Participants must have measurable disease documented by CT or MRI. Measurable disease
must be assessed within 28 days prior to registration. Non-measurable disease must be
assessed within 42 days prior to registration. The CT from a combined positron
emission tomography (PET)/CT may be used only if it is of diagnostic quality. All
known sites of disease must be assessed and documented on the Baseline Tumor
Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
Participants whose only measurable disease is within a previous radiation therapy port
must demonstrate clearly progressive disease (in the opinion of the treating
investigator) prior to registration
• Participants with known brain metastases must have a CT/MRI scan to evaluate for
central nervous system (CNS) disease and show no evidence of progression within 42
days prior to registration
• Participants must have completed any CNS-directed therapy and/or local therapy for
spinal cord compression at least 28 days prior to registration
• Participants must not have spinal cord compression or brain metastases unless: (1)
metastases have been locally treated and have remained clinically controlled and
asymptomatic for at least 14 days prior to registration, AND (2) participant has no
residual neurological dysfunction and has been off corticosteroids for at least 24
hours prior to registration
• Participants must not have leptomeningeal disease
• Participants must have progressed within 6 months of taxane-based therapy in the
neoadjuvant/adjuvant or metastatic setting
• Participants must not have received any prior AKT inhibitor (e.g., capivasertib or
ipatasertib); prior PI3K/mTOR inhibitor is acceptable
• Participants must not be planning to receive any concurrent chemotherapy,
immunotherapy, biologic, radiation, or hormonal therapy for cancer treatment while
receiving treatment on this study
• Participants must be >= 18 years of age
• Participants must be able to swallow oral medications whole
• Participants must have a pre-study history and physical exam done within 28 days prior
to registration
• Participants must have a Zubrod performance status of 0-2 within 28 days prior to
registration
• Participants must have adverse events resolved =< grade 1 related to any prior
therapy, except alopecia within 14 days prior to registration
• Participants with neuropathy must have resolved to < grade 2 within 14 days prior to
registration
• Leukocytes >= 3 x 10^3/uL (within 28 days prior to registration)
• Absolute neutrophil count >= 1.5 x 10^3/uL (within 28 days prior to registration)
• Platelets >= 100 x 10^3/uL (within 28 days prior to registration)
• Total bilirubin =< institutional upper limit of normal (ULN) unless history of
Gilbert's disease. Participants with history of Gilbert's disease must have total
bilirubin =< 5 x institutional ULN (within 28 days prior to registration)
• Aspartate aminotransferase (AST) & alanine aminotransferase (ALT) =< 3 x institutional
ULN (within 28 days prior to registration)
• Participants must have adequate cardiac function, class IIB (2B) or better.
Participants with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification
• Participants must have a measured OR calculated creatinine clearance >= 50 mL/min
using the following Cockcroft-Gault formula. This specimen must have been drawn within
28 days prior to registration
• Participants with known human immunodeficiency virus (HIV)-infection must be receiving
anti-retroviral therapy and have an undetectable viral load test on the most recent
test results obtained within 6 months prior to registration
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have
undetectable HBV viral load on suppressive therapy within 28 days prior to
registration
• Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured. Participants with HCV infection who are currently on treatment must
have an undetectable HCV viral load within 28 days prior to registration
• Participants must have an electrocardiography (ECG) performed (if clinically indicated
with a corrected QTc interval of =< 470 msec) within 28 days prior to registration
• Participants must not have a history of allergic reactions attributed to compounds of
similar chemical or biologic composition to ipatasertib and/or paclitaxel
• Participants must not have an active small/large bowel inflammation such as ulcerative
colitis or Crohn's disease
• Participants must not have grade 2 or higher uncontrolled intercurrent illness
• NOTE: To receive an agent, participant must not have any uncontrolled
intercurrent illness requiring antibiotic/antiviral/antifungal therapy or
interventional procedures. Participants with infections unlikely to be resolved
within 2 weeks following registration should not be considered for the trial
• Participants must not have a known grade 2 or higher uncontrolled or untreated
hypercholesterolemia or hypertriglyceridemia
• Participants must not have any of the following:
• Cirrhosis at a level of Child-Pugh B (or worse),
• Cirrhosis (any degree) and a history of hepatic encephalopathy, or
• Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful
ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
• Participants must not be receiving any medications or substances that are inhibitors
or inducers of CYP3A. Treatment with strong CYP3A inhibitors or strong CYP3A inducers
within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to
initiation of study drug is prohibited.
• NOTE: Because the lists of these agents are constantly changing, it is important
to regularly consult a frequently updated medical reference. As part of the
enrollment/informed consent procedures, the participant will be counseled on the
risk of interactions with other agents, and what to do if new medications need to
be prescribed or if the participant is considering a new over-the-counter
medicine or herbal product. The participant wallet card should be presented to
the participant
• Participants must not have baseline fasting glucose (after 8-hour fast) > 160 mg/dL
(8.9 mmol/L) within 28 days prior to registration
• Participants with known diabetes mellitus must not require insulin therapy or have a
baseline fasting glucose >150 mg/dL (8.3 mmol/L) or high glycosylated hemoglobin
(Hb)A1c, (>= 8.0%), suggesting poorly controlled diabetes
• Participants who are on a stable dose of oral diabetes medication >= 2 weeks prior to
initiation of study drug treatment are eligible for enrollment
• Participants with a prior or concurrent malignancy whose natural history or treatment
(in the opinion of the treating physician) must not have a potential to interfere with
the safety or efficacy assessment of the investigational regimen
• Participants must not have lung disease requiring active systemic therapy or placing
participants at increased risk of toxicity related to study-directed therapy
including, but not limited to pneumonitis, interstitial lung disease, idiopathic
pulmonary fibrosis, cystic fibrosis, aspergillosis, active tuberculosis, or history of
opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
• Participants must not be pregnant or nursing. Individuals who are of reproductive
potential must have agreed to use an effective contraceptive method with details
provided as a part of the consent process. A person who has had menses at any time in
the preceding 12 consecutive months or who has semen likely to contain sperm is of
"reproductive potential". In addition to routine contraceptive methods, "effective
contraception" also includes surgery intended to prevent pregnancy (or with a
side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy,
bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the
semen
• Participants must not have psychiatric illness/social situations that would limit
compliance with study requirements
Locally Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Malignant Solid Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) (ACTION)
This is a randomized, double-blind, placebo-controlled, parallel-group, international, Phase
3 study in patients with newly diagnosed H3 K27M-mutant diffuse glioma to assess whether
treatment with ONC201 following frontline radiotherapy will extend overall survival and
progression-free survival in this population. Eligible participants will have histologically
diagnosed H3 K27M-mutant diffuse glioma and have completed standard frontline radiotherapy.
Ankush Bhatia, M.D.
All
Not specified
Phase 3
This study is NOT accepting healthy volunteers
NCT05580562
Show full eligibility criteria
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Inclusion Criteria:
1. Able to understand the study procedures and agree to participate in the study by
providing written informed consent (by participant or legally authorized
representative), and assent when applicable.
2. Body weight ≥ 10 kg at time of randomization.
3. Histologically diagnosed H3 K27M-mutant diffuse glioma (new diagnosis). Detection of a
missense K27M mutation in any histone H3-encoding gene detected by testing of tumor
tissue (immunohistochemistry [IHC] or next-generation sequencing [NGS] in a Clinical
Laboratory Improvement Amendments [CLIA]-certified or equivalent laboratory). [Site to
provide (as available): ≥ 10 unstained formalin-fixed paraffin-embedded (FFPE) slides
from tumor tissue.]
4. At least one, high-quality, contrast-enhanced MRI of the brain obtained prior to
starting radiotherapy for submission to sponsor's imaging vendor for central read. For
participants who had a surgical resection, this scan must be post-resection; for
participants who did not have a resection, this scan may be pre- or post-biopsy.
5. At least one, high-quality, contrast-enhanced MRI of the brain obtained 2 to 6 weeks
after completion of frontline radiotherapy. If unable to obtain contrast-enhanced
imaging due to lack of venous access after multiple attempts, a patient may still be
eligible after collection of a nonenhanced MRI of the brain. [Site to also provide all
available MRIs completed prior to initiating treatment with study intervention.]
6. Received frontline radiotherapy
1. Initiated radiotherapy within 12 weeks from the initial diagnosis of H3
K27M-mutant diffuse glioma.
2. Completed radiotherapy within 2 to 6 weeks prior to randomization
3. Completed standard fractionated radiotherapy (eg. 54 to 60 Gy in 28 to 33
fractions given over approximately 6 weeks or hypofractionated radiotherapy (eg.
40 Gy in 15 fractions given over approximately 3 weeks).
7. Karnofsky Performance Status or Lansky Performance Status ≥ 70 at time of
randomization.
8. Stable or decreasing dose of corticosteroids and anti-seizure medications for 7 days
prior to randomization, if applicable. Stable steroid dose is defined as ≤ 2 mg/day
increase (based on dexamethasone dose or equivalent dose of an alternative steroid).
Exclusion Criteria:
1. Primary spinal tumor.
2. Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter
and diffuse involvement of the pons.
3. Evidence of leptomeningeal spread of disease or cerebrospinal fluid dissemination.
4. Any known concurrent malignancy.
5. New lesion(s) outside of the radiation field.
6. Received whole-brain radiotherapy.
7. Received proton therapy for glioma.
8. Use of any of the following treatments within the specified time periods prior to
randomization:
1. ONC201 or ONC206 at any time.
2. Systemic bevacizumab (includes biosimilars) at any time since the initial
diagnosis of H3 K27M-mutant diffuse glioma.
3. Temozolomide within past 3 weeks.
4. Tumor treating fields at any time.
5. DRD2 antagonist within past 2 weeks.
6. Any investigational therapy within past 4 weeks.
7. Strong CYP3A4 inhibitors within 3 days.
8. Strong CYP3A4 inducers (includes enzyme-inducing antiepileptic drugs) within 2
weeks.
9. Laboratory test results meeting any of the following parameters within 2 weeks prior
to randomization:
1. Absolute neutrophil count < 1.0 × 109/L or platelets < 75 × 109/L.
2. Total bilirubin > 1.5 × upper limit of normal (ULN) (participants with Gilbert's
syndrome may be included with total bilirubin > 1.5 × ULN if direct bilirubin is
≤ 1.5 × ULN).
3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN.
4. Creatinine clearance ≤ 60 mL/min as calculated by the Cockcroft Gault equation
(or estimated glomerular filtration rate < 60 mL/min/1.73 m2).
10. QTc > 480 msec (based on mean from triplicate electrocardiograms) during screening.
11. Known hypersensitivity to any excipients used in the study intervention formulation.
12. Pregnant, breastfeeding, or planning to become pregnant while receiving study
intervention or within 3 months after the last dose. Participants of childbearing
potential must have a negative serum pregnancy test within 72 hours prior to receiving
the first dose of study intervention.
13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring systemic therapy or psychiatric illness/social situations that
would limit compliance with study requirements.
14. Any other condition (eg, medical, psychiatric, or social) that, in the opinion of the
investigator, may interfere with participant safety or the ability to complete the
study according to the protocol.
Brain and Nervous System, Brain/Central Nervous System, H3 K27M, Glioma
A Randomized, Double-Blind, Placebo-Controlled Trial of IkT-148009 in Untreated Parkinson's Disease
This study investigates the safety and tolerability of drug IkT-148009 in untreated
Parkinson's disease volunteers (30 to 80 years old). It also looks at the pharmacokinetics of
IkT-148009 in the body and evaluates the effect of IkT-148009 on motor and non-motor features
of the disease. This 12 week study is designed to be 3:1 randomized across 3 doses of
IkT-148009 or placebo. Each participant will self-administer one of 3 doses or placebo of
IkT-148009 once daily (QD) with food for 12 weeks. For more information, visit our website:
www.the201trial.com
Kathleen Shannon
All
30 Years to 80 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT05424276
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Inclusion Criteria
1. Participants who are diagnosed with PD consistent with UK Brain Bank criteria and MDS
Research Criteria; must include bradykinesia with sequence effect and motor asymmetry.
2. Receiving no anti-parkinsonian therapy
3. Modified Hoehn/Yahr Stage < 3.0
4. Montreal Cognitive Assessment ≥ 24
5. Patient expected to be able to participate in trial without need for additional
anti-parkinsonian therapy
Sex and Contraceptive/Barrier Requirements:
1. Male participants must agree to practice an acceptable method of highly effective
birth control from the screening visit, while on study and for 30 days after receiving
the last dose of study drug. Highly effective methods of birth control include sexual
abstinence, vasectomy, or a condom with spermicide (men) in combination with their
partner's highly effective method.
2. Female participants of childbearing potential and male participants with female
partners of childbearing potential must agree to either remain abstinent or use
adequate and reliable contraception throughout the study and at least 30 days after
the last dose of study drug has been taken.
Informed Consent:
1. Capable of giving signed ICF as described in Appendix 1 which includes compliance with
the requirements and restrictions listed in the ICF and in this protocol.
Other Inclusions:
1. Approved as an appropriate and suitable candidate by the EAC.
Exclusion Criteria
1. Diagnosis/suspicion of secondary or atypical parkinsonism
2. Previous procedure or surgery for PD, or anticipation of these during the study
3. High likelihood of needing anti-parkinsonian treatment over the study period, in the
opinion of the investigator
4. Clinically significant orthostatic hypotension
5. Clinically significant hallucinations requiring antipsychotic use in the 12 months
prior to Screening
6. Clinically significant medical, surgical, psychiatric, or laboratory abnormalities in
the judgement of the treating investigator or the EAC
Prior/Concomitant Therapy:
1. Past treatment with levodopa, dopaminergic agonists, monoamine oxidase-B inhibitors,
supplements containing levodopa (i.e. Mucana pruriens), or A2A antagonists for more
than 28 days, or treatment with any of these medications or supplements within 28 days
prior to screening
2. Past treatment with irreversible monoamine oxidase-B inhibitors (e.g., selegiline) for
more than 28 days; must be discontinued for at least 90 days before screening
3. Currently receiving moderate or strong Cytochrome P450 (CYP) 3A4/5 inducers or
CYP3A4/5 inhibitors (except for topical administration)
4. Currently receiving any antipsychotic, metoclopramide, reserpine, or amphetamine.
Prior/Concurrent Clinical Study Experience:
1. Current participation in another investigational clinical trial and/or receipt of any
investigational medication within 90 days prior to screening
2. Previous randomization into this or another IkT-148009 study
Diagnostic Assessments:
1. Active suicidal ideation within one year prior to screening visit, as determined by
the Columbia Suicide Rating Scale (answer of "yes" on question 4 or 5)
2. Current diagnosis or history of substance abuse (excluding nicotine or caffeine) by
Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria
3. Medical or recreational use of marijuana in the 3 months prior to the screening visit
4. Any social or behavioral reason that would preclude completion of the study, in the
judgement of the investigator
5. Any skin condition that would interfere with obtaining adequate samples
6. Evidence of advanced, age-related macular degeneration (neovascular or geographic
atrophy) or intermediate macular degeneration as defined by Beckman classification
(Large drusen > 125 um and/or any AMD pigmentary abnormalities). Evidence of
retina/choroid neovascularization from any cause. Evidence of central serous
retinopathy.
7. Abnormal amylase and/or lipase at screening (may be repeated during screening period)
8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than
2.5 times the upper limit of normal (ULN)
9. Significant renal impairment as determined by the following criteria:
• Creatinine clearance (CrCL) less than or equal to 60 mL/min for subjects < 65
years of age
• Creatine clearance (CrCL) greater than or equal to 55 mL/min and the absence of
proteinuria or hematuria for subjects ≥ 65 years of age
10. Currently lactating, pregnant or planning on becoming pregnant during the study
Randomized Study in Children and Adolescents With Migraine: Acute Treatment
The purpose of this study is to test the safety and efficacy of BHV-3000 versus placebo in
the acute treatment of moderate or severe migraine in children and adolescents.
Ali Zandieh
All
6 Years to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04649242
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Inclusion Criteria:
1. History of migraine (with or without aura) for > 6 months before Screening according
to the IHS Classification ICHD-319 specifications for pediatric migraine. History may
be verified using both medical records and recall by the participant and/or
participant's parent(s)/legal representative(s).
2. History of 1 to 8 moderate or severe attacks per month during the 2 months prior to
enrollment, with attacks lasting > 3 hours without treatment, and attacks occurring at
intervals > 24 hours.
3. Prophylactic migraine medication are permitted if the dose has been stable for at
least 12 weeks prior to the Baseline Visit, and the dose is not expected to change
during the course of the study.
1. Participants may remain on one (1) medication with possible migraine prophylactic
effects, excluding CGRP antagonists [biologic or small molecule], during the
treatment phases.
2. Concomitant use of a CGRP antagonist, such as erenumab or fremanezumab, is
prohibited.
3. Previously discontinued prophylactic migraine medication must have done so at
least 90 days prior to the Screening Visit.
4. Verbally distinguish between migraine and other types of headaches.
5. Participants must have a weight > 40 kg at the Screening Visit.
6. Adequate venous access for blood sampling.
7. Male and female participants ≥ 6 to < 18 years of age (participants must not reach
their 18th birthday during the study).
Exclusion Criteria:
1. History of cluster headache or hemiplegic migraine headache.
2. Confounding and clinically significant pain syndrome that may interfere with the
participant's ability to participate in this study.
3. Current psychiatric condition that is uncontrolled and/or untreated for a minimum of 6
months prior to the Screening Visit. Participants with a lifetime history of psychosis
and/or mania.
4. History of suicidal behavior or major psychiatric disorder.
5. Current diagnosis or history of substance abuse; positive drug test at Screening.
6. History of moderate or severe head trauma or other neurological disorder (including
seizure disorder) or systemic medical disease that is likely to affect central nervous
system functioning.
7. Recent or planned surgery, requiring general anesthesia, <8 weeks prior to the
Screening Visit.
8. Participant has had gastrointestinal surgery that interferes with physiological
absorption and motility (i.e., gastric bypass, duodenectomy, or gastric banding).
9. Current diagnosis of viral hepatitis or a history of liver disease.
10. Conditions considered clinically relevant in the context of the study such as
uncontrolled hypertension (high blood pressure), diabetes, a life-threatening allergy
Long-term Safety Study of Rimegepant in Pediatric Subjects for the Acute Treatment of Migraine
The purpose of this study is to test the long-term safety of rimegepant in the acute
treatment of moderate or severe migraine in children and adolescents (≥ 6 to < 18 years of
age).
Ali Zandieh
All
6 Years to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04743141
Show full eligibility criteria
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Inclusion Criteria:
1. History of migraine (with or without aura) for ≥ 6 months before Screening
2. History of 1 to 8 moderate or severe attacks per month during the 2 months prior to
enrollment.
3. 1 or more migraine days requiring treatment during the Observation Phase.
4. Prophylactic migraine medication is permitted if the dose has been stable for at least
12 weeks prior to the Baseline Visit
5. Ability to distinguish between migraine and other types of headaches.
6. Weight ≥ 40 kg at the Screening Visit.
7. Adequate venous access for blood sampling.
8. Male and female participants ≥ 6 to < 18 years of age (participants must not reach
their 18th birthday before enrollment into the study)
Exclusion Criteria:
1. History of cluster headache or hemiplegic migraine headache.
2. Confounding and clinically significant pain syndrome
3. Current uncontrolled and/or untreated psychiatric condition for a minimum of 6 months
prior to the Screening Visit (lifetime history of psychosis and/or mania are
excluded).
4. History of suicidal behavior or major psychiatric disorder.
5. Current diagnosis or history of substance abuse; positive drug test at Screening.
Acute Treatment of Migraine, Other, Brain & Neurological
Study of DF9001 in Patients With Advanced Solid Tumors
DF9001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell
activation signals to specific receptors on cancer cells. The study will occur in two phases.
The first phase will be a dose escalation phase, enrolling patients with various types of
solid tumors that express epidermal growth factor receptor (EGFR). A combination therapy
cohort will be opened for enrollment, DF9001 + nivolumab. The second phase will include a
dose expansion using the best dose selected from the first phase of the study. Multiple
cohorts will be opened with eligible patients having selected solid tumors.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05597839
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Inclusion Criteria:
General (applies to all cohorts)
1. Signed written informed consent.
2. Male or female patients aged ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry
and an estimated life expectancy of at least 3 months.
4. Adequate hematological function.
5. Adequate hepatic function.
6. Adequate renal function.
7. Effective contraception for women of child bearing potential (WOCBP) patients as
defined by World Health Organization (WHO) guidelines for 1 "highly effective" method
or 2 "effective" methods.
Inclusion Criteria:
Dose Escalation (Monotherapy and Combination)
1. Histologically or cytologically proven locally advanced or metastatic solid tumors of
epithelial origin with documented EGFR expression on tumor tissue by IHC and must have
progressed on standard of care therapy.
2. Evidence of objective disease, but participation does not require a measurable lesion.
Inclusion Criteria:
Safety PK/PD Expansion Cohorts
1. Histologically or cytologically proven locally advanced or metastatic solid tumor from
the following list, where standard therapy has failed, that has been confirmed to have
EGFR expression via archival or fresh biopsy tissue prior to study enrollment.
i. NSCLC ii. HNSCC iii. CRC iv. Esophageal adenocarcinoma v. Gastric cancer vi. Renal
cell carcinoma vii. Pancreatic cancer
2. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
3. Able and willing to have a fresh tumor biopsy obtained during the screening window and
an on-treatment biopsy for pharmacodynamic analysis.
Inclusion Criteria:
Head and Neck Squamous Cell Carcinoma (HNSCC) Expansion Cohorts
1. Histologically or cytologically documented relapsed or metastatic HNSCC that has been
confirmed to have EGFR expression via archival or fresh biopsy tissue prior to study
enrollment. Primary tumor locations include oropharynx, oral cavity, hypopharynx, or
larynx. Participants may not have a primary tumor site of nasopharynx (any histology).
2. Participants must have radiographic disease progression while on or after having
received both platinum-based chemotherapy and an anti-PD-(L)1 antibody, administered
either concurrent or sequentially.
3. Documented EGFR expression by IHC.
4. Able and willing to have a fresh tumor biopsy obtained during the screening window and
an on-treatment biopsy for pharmacodynamic analysis.
Inclusion Criteria:
Colorectal Cancer (CRC) Expansion Cohorts
1. Histologically or cytologically documented relapsed or metastatic colorectal cancer
that has been confirmed to have EGFR expression via archival or fresh biopsy tissue
prior to study enrollment.
2. Must have received 1 line of either FOLFOX, CAPOX, FOLFIRI, or FOLFOXIRI with or
without a biological agent. Prior treatment with an anti-EGFR antibody is required for
RAS wild-type participants.
3. Participants cannot be known mismatch repair (MMR)/MSI high.
4. Participants must not have received an anti-PD-(L)1.
5. Participants must have radiographic disease progression while or after receiving
treatment for their advanced (recurrent/unresectable/metastatic) disease.
6. Presence of at least 1 tumor lesion accessible for biopsy. A fresh tumor biopsy must
be obtained and shipped for analysis at the Sponsor-designated laboratory during the
screening window and while on study treatment in accordance with the study Laboratory
Manual.
Inclusion Criteria:
Non-Small Cell Lung Cancer (NSCLC) Expansion Cohorts
1. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV (per
the 7th IASCLC classification of NSCLC), or recurrent disease that has been confirmed
to have EGFR expression via archival or fresh biopsy tissue prior to study enrollment.
2. Patients must have recurrent or progressive disease during or after first line
combination therapy with checkpoint inhibitors and platinum-based chemotherapy. They
must not have received any subsequent lines of therapy.
3. Patients with Stage IIIB must be ineligible for local therapies with curative intent
(eg, radiotherapy or surgery).
4. Patients must have received and progressed on or after anti-PD-(L)1 therapy including
those with actionable genomic alterations.
5. Status for actionable mutations (EGFR, ALK, ROS1, RET, etc.) must be known (when
testing is available as per country/region standard of care practices); patients with
actionable mutations must have received and progressed on, have been intolerant to, or
not be a candidate for standard TKIs (as available per country/region standard of care
practices).
6. Presence of at least 1 tumor lesion accessible for biopsy. A fresh tumor biopsy must
be obtained and shipped for analysis at the Sponsor-designated laboratory during the
screening window and while on study treatment in accordance with the study Laboratory
Manual.
Exclusion Criteria:
1. Participants must not have had chemotherapy, radiotherapy (other than palliative
bone-directed radiotherapy), or major surgery, or received another investigational
agent within 28 days or 5-half-lives of the drug (if known), whichever is shorter,
before the start of study treatment.
2. Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy [except for
palliative bone-directed radiotherapy], immune therapy, or cytokine therapy [except
for erythropoietin]), major surgery (excluding prior diagnostic biopsy), concurrent
systemic therapy with steroids or other immunosuppressive agents, or use of any
investigational drug within 28 days or 5-half-lives of the drug (if known), whichever
is shorter, before the start of study treatment. Short-term administration of systemic
steroids (eg, for allergic reactions or the management of irAEs) is allowed.
Note: Participants receiving bisphosphonate or denosumab are eligible, provided
treatment was initiated at least 14 days before the first dose of DF9001.
3. Previous malignant disease other than the target malignancy to be investigated in this
study within the last 3 years, with the exception of basal or squamous cell carcinoma
of the skin, low-grade prostate cancer (Gleason score of ≤6), or cervical carcinoma in
situ.
4. Life expectancy of less than 3 months.
5. Participants with brain metastases are excluded, unless all of the following criteria
are met:
• Central nervous system (CNS) lesions are asymptomatic, previously treated and no
active therapy is required (i.e., no steroids for edema).
• Imaging demonstrates stability of disease 28 days from last treatment for CNS
metastases.
6. Receipt of any organ transplantation, including autologous or allogeneic stem-cell
transplantation.
7. Significant acute or chronic infections (including historic positive test for human
immunodeficiency virus [HIV], or active or latent hepatitis B or active hepatitis C
tested during the screening window). If HBsAg is negative and the anti-hepatitis B
core antibody is positive, then hepatitis B viral DNA load must be undetectable.
8. Preexisting autoimmune disease (except for participants with vitiligo) needing
treatment with systemic immunosuppressive agents for more than 28 days within the last
3 years, or clinically relevant immunodeficiencies (eg, dysgammaglobulinemia or
congenital immunodeficiencies). Participants with a history of immune related
endocrinopathies (e.g. hypothyroidism, type 1 diabetes mellitus [TIDM] and adrenal
insufficiency) that are stable on hormone replacement therapy may be eligible for this
study.
9. Participants with a known medical history that may place them at risk of known
toxicities of EGFR-blockage.
• History of or ongoing keratitis, ulcerative keratitis, or corneal perforation,
• History of cardiopulmonary arrest unless this was caused by an acute, reversible
etiology that is no longer present.
• History of or ongoing pulmonary fibrosis or interstitial lung disease.
10. Known severe hypersensitivity reactions to monoclonal antibodies (≥Grade 3 of the
NCI-CTCAE v5.0), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more
features of partly controlled asthma).
11. Persisting toxicity related to prior therapy >Grade 1 NCI-CTCAE v5.0; however,
alopecia ≤Grade 2, endocrinopathies ≤Grade 2, and sensory neuropathy ≤Grade 2 is
acceptable.
12. Participants who have received an anti-PD-(L)1 as a previous line of therapy are
eligible for the study, unless they have experienced either:
• a Grade 3 or 4 drug-related toxicity during and attributed to treatment with the
anti-PD-(L)1.
• a Grade 2 drug-related toxicity that impacted either the lungs or the nervous
system, caused by the administration of the anti-PD-(L)1.
13. Pregnancy or lactation in females during the study.
14. Known alcohol or drug abuse.
15. Serious cardiac illness or medical conditions, including but not limited to:
• History of New York Heart Association class III or IV heart failure or systolic
dysfunction (left ventricular ejection fraction [LVEF] <55%).
• High-risk uncontrolled arrhythmias (eg, tachycardia with a heart rate >100/min at
rest).
• Significant ventricular arrhythmia (ventricular tachycardia) or higher-grade
atrioventricular (AV) block (eg, AV-block, second degree AV block Type 2 [Mobitz
2], or third-degree AV-block).
• Angina pectoris requiring anti-anginal medication.
• Clinically significant valvular heart disease.
• Evidence of transmural infarction on ECGs.
• Poorly controlled hypertension (defined as systolic >160 mm Hg or diastolic >100
mm Hg).
• Clinically relevant uncontrolled cardiac risk factors, clinically relevant
pulmonary disease, or any clinically relevant medical condition in the opinion of
the Investigator that may limit participation in this study.
• Severe dyspnea at rest due to complications of advanced malignancy or requiring
supplementary oxygen therapy.
16. All other significant diseases (eg, inflammatory bowel disease), which, in the opinion
of the Investigator, might impair the participant's ability to participate.
17. Any psychiatric condition that would prohibit the understanding or rendering of
informed consent.
18. Legal incapacity or limited legal capacity.
19. Incapable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the ICF and in this protocol.
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus, Solid Tumor, Adult
Testing the Addition of Whole Brain Radiotherapy Using a Technique That Avoids the Hippocampus to Stereotactic Radiosurgery in People With Cancer That Has Spread to the Brain and Come Back in Other Areas of the Brain After Earlier Stereotactic Radiosurgery
This phase III trial compares the effect of adding whole brain radiotherapy with hippocampal
avoidance and memantine to stereotactic radiosurgery versus stereotactic radiosurgery alone
in treating patients with cancer that has spread to the brain and come back in other areas of
the brain after earlier stereotactic radiosurgery. Hippocampus avoidance during whole-brain
radiation therapy decreases the amount of radiation that is delivered to the hippocampus,
which is a brain structure that is important for memory. The medicine memantine is also often
given with whole brain radiation therapy because it may decrease the risk of side effects of
radiation on thinking and memory. Stereotactic radiosurgery delivers a high dose of radiation
only to the small areas of cancer in the brain and avoids the surrounding normal brain
tissue. Adding whole brain radiotherapy with hippocampal avoidance and memantine to
stereotactic radiosurgery may be effective in shrinking or stabilizing cancer that has spread
to the brain and returned in other areas of the brain after receiving stereotactic
radiosurgery.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04588246
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Inclusion Criteria:
• Patients must have developed their first or second distant brain relapse(s) at least 8
weeks after upfront SRS and within 21 days prior to randomization
• Distant brain relapse lesions to be treated must measure =< 3.0 cm in maximal
extent and total volume of distant brain relapses to be treated must measure < 30
mL on the contrast-enhanced diagnostic magnetic resonance imaging (MRI) brain
scan obtained within 21 days prior to randomization
• Distant brain relapse lesions must be diagnosed on MRI, which will include the
following elements:
• REQUIRED MRI ELEMENTS
• Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D)
spoiled gradient (SPGR). Acceptable 3D SPGR sequences include
magnetization-prepared 3D gradient recalled echo (GRE) rapid gradient
echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (brain volume
imaging) or 3D fast FE (field echo). The T1-weighted 3D scan should use
the smallest possible axial slice thickness, not to exceed 1.5 mm
• Pre-contrast T1 weighted imaging (3D imaging sequence strongly
encouraged)
• A minimum of one axial T2 fluid attenuated inversion recovery (FLAIR)
(preferred) or T2 sequence is required. This can be acquired as a 2D or
3D image. If 2D, the images should be obtained in the axial plane
• ADDITIONAL RECOMMENDATIONS
• Recommendation is that an axial T2 FLAIR (preferred) sequence be
performed instead of a T2 sequence
• Recommendation is that that pre-contrast 3D T1 be performed with the
same parameters as the post-contrast 3D T1
• Recommendation is that imaging be performed on a 3 Tesla (3T) MRI
• Recommendation is that the study participants be scanned on the same
MRI instrument at each time point
• Recommendation is that if additional sequences are obtained, these
should meet the criteria outlined in Kaufmann et al., 2020
• If additional sequences are obtained, total imaging time should not
exceed 60 minutes
• Brain metastasis velocity (BMV) since upfront SRS must be >= 4 brain metastases/year
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry
• Pathologically (histologically or cytologically) proven diagnosis of non-small cell
lung cancer, melanoma, breast cancer, renal cell carcinoma, or gastrointestinal cancer
within 10 years prior to randomization. If the original histologic proof of malignancy
is greater than 10 years, then pathological (i.e., more recent) confirmation is
required (e.g., from a systemic metastasis or brain metastasis)
• Other histologies are not permitted
• History and physical examination within 28 days prior to randomization
• Karnofsky performance status of >= 70 within 28 days prior to randomization
• Calculated creatinine clearance (CrCl) >= 30 ml/min (within 28 days prior to
randomization)
• Blood urea nitrogen (BUN) within 1.5 times the institutional upper limit of normal
(ULN) (e.g., if the ULN is 20 mg/dL, then BUN up to 30 mg/dL is permitted) (within 28
days prior to randomization)
• Negative urine or serum pregnancy test (in women of childbearing potential) within 14
days prior to randomization
Exclusion Criteria:
• Prior WBRT or prophylactic cranial irradiation
• Local relapse of metastasis previously treated with upfront SRS (i.e., relapse outside
previously SRS-treated metastases is allowed)
• Brain metastases from primary germ cell tumor, small cell carcinoma, or lymphoma
• Definitive leptomeningeal metastasis
• Planned cytotoxic chemotherapy on the same day as SRS or HA-WBRT; concurrent
immunotherapy is permitted
• Radiographic evidence of enlargement or other architectural distortion of the lateral
ventricles, including placement of external ventricular drain or ventriculoperitoneal
shunt
• Known history of demyelinating disease such as multiple sclerosis
• Inability to swallow pills
• Contraindication to MR imaging such as non-MR conditional implanted metal devices or
unknown metallic foreign bodies, or contraindication to gadolinium contrast
administration during MR imaging, such as anaphylactic allergy that cannot be
adequately addressed with pre-contrast medications or acute kidney injury
• Contraindications to memantine, including:
• Allergy, including prior allergic reaction to memantine
• Intractable seizures on adequate anticonvulsive therapy-more than 1 seizure per
month for the past 2 months
• Current use of N-methyl-D-aspartate (NMDA) agonist
• Current alcohol or drug abuse, which can exacerbate lethargy/dizziness with
memantine
• Severe, active co-morbidity defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of randomization
• Chronic obstructive pulmonary disease exacerbation or other acute respiratory
illness precluding study therapy at the time of randomization
• Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic
disease
• Renal tubular acidosis or metabolic acidosis
• Human immunodeficiency virus (HIV) positive with CD4 count < 200
cells/microliter. Note that patients who are HIV positive are eligible, provided
they are under treatment with highly active antiretroviral therapy (HAART) and
have a CD4 count >= 200 cells/microliter within 30 days prior to randomization.
Note also that HIV testing is not required for eligibility for this protocol
• Pregnant or lactating women, or women of childbearing potential and men who are
sexually active and not willing/able to use medically acceptable forms of
contraception; this exclusion is necessary because the medication and radiation
involved in this study has unknown effects on the unborn fetus
Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Metastatic Digestive System Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Metastatic Melanoma, Metastatic Renal Cell Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8, Recurrent Brain Neoplasm, Stage IV Lung Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8, Brain and Nervous System, Brain/Central Nervous System
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