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EPPIC-Net: Platform Protocol to Assess Treatments for Painful Diabetic Peripheral Neuropathy
This is a Platform Protocol to perform Phase II clinical trials in The Early Phase Pain
Investigation Clinical Network (EPPIC-Net), under The Helping to End Addiction Long-termSM
Initiative, or NIH HEAL InitiativeSM, related to the treatment of Painful Diabetic Peripheral
Neuropathy (PDPN) in a platform setting to test multiple assets under a single protocol.
Nalini Sehgal
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05476276
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Inclusion Criteria:
1. Able to provide informed consent. Legally Authorized Representatives (LARs) will not
be permitted.
2. 18 years of age and older
3. Diagnosis of diabetes mellitus
4. Meets the Toronto Criteria for probable clinical sensorimotor polyneuropathy, with
PDPN symptoms present for at least six months. This is defined as a combination of
symptoms and signs with any two or more of the following (must be present bilaterally
in the distal lower extremities): neuropathic symptoms, decreased distal sensation, or
unequivocally decreased (or absent) ankle reflexes. Specifically:
a. The presence of any neuropathic symptoms on either the "Douleur Neuropathique en 4
Questions" (DN4) or the EPPIC-Net Neuropathy Exam will suffice to demonstrate
"neuropathic symptoms." b. Decreased distal sensation is satisfied by any of the
following: i. "Yes" is checked at least once under Question 3 of the DN4 which queries
hypoesthesia to touch and pinprick.
ii. At least one score of "reduced" or "absent" on the right AND at least one score of
"reduced" or "absent" on the left in any of the following items from the EPPIC-Net
Neuropathy Exam:
• Pin sensation in segments 1 or 2 (i.e. the toes and feet)
• Vibration at the great toe
• Joint position at the great toe
• Light touch/touch pressure at the great toe
• Temperature at the great toe
• Monofilament at the great toe c. Decreased or absent ankle reflexes is satisfied
by a score of "reduced" or "absent" on the right AND left in the "Ankle reflex"
item in the EPPIC-Net Neuropathy Exam.
5. A score of at least 4 on the "Douleur Neuropathique en 4 Questions" (DN4).
6. Pain reporting during a pre-defined 7-day screening period meets study criteria (to be
established using a centrally-administered screening algorithm) which may account for
mean pain intensity reported, variability in reported values, and adherence in
reporting.
7. Patient reported daily 11-point NRS (for average and worst pain over the last 24
hours) is completed on at least 5 out of the 7 days in the baseline period.
8. Participants must be willing and able to comply with scheduled visits, the treatment
schedule, laboratory testing, and other requirements of the study (e.g., completion of
app-based daily reporting).
9. Females may be included if they meet at least one of the following criteria (note that
individual ISAs may specify more stringent measures to prevent pregnancy):
a. Are not of childbearing potential, defined as one or more of the following: i.
Post-menopausal for at least 1 year ii. Surgically sterile (bilateral tubal ligation,
bilateral oophorectomy, or hysterectomy) iii. XY genotype iv. Turner syndrome v.
Uterine agenesis. b. Are completely abstinent from sexual activity capable of
resulting in pregnancy (as part of their preferred and usual lifestyle). This will
include females whose sole sexual partner is a male who has undergone surgical
sterilization or vasectomy.
c. Women of childbearing potential will agree to practice an effective form of two
types of birth control, which are defined as those, alone or in combination, that
result in a low failure rate (i.e., less than 1% per year) when used consistently and
correctly. This must be done before, throughout, and for 30 days after the last dose
of study drug. Acceptable methods are: i. Hormonal methods such as the vaginal ring,
or oral, implantable, injectable, or transdermal contraceptives for a minimum of 1
full cycle (based on the participant's usual menstrual cycle period) before study drug
administration.
ii. Intrauterine device. iii. Barrier method of contraception: condoms with or without
a spermicidal agent, diaphragm or cervical cap with spermicide
10. Specific requirements of male participants (regarding contraception) will be defined
in the ISAs based on the potential toxicity profile of the asset.
Exclusion Criteria:
3.1.1. Neuropathy Confound Exclusion Criteria
1. Peripheral neuropathy caused by a condition other than diabetes (e.g. HIV,
cancer/chemotherapy-induced, other medication-induced, alcohol-induced, hereditary,
autoimmune neuropathies, uncontrolled or untreated hypothyroidism). Note that
participants will not be tested for HIV, this will be established by patient report or
review of the medical record.
2. Other significant pain conditions involving the same area as the neuropathy (e.g.
physical deformity of the feet, plantar fasciitis, lumbosacral radiculopathy with
distal lower extremity pain, fibromyalgia involving the lower limbs, Morton's
neuroma).
3. Other pain conditions not involving the same area as the neuropathy which (in the
opinion of the investigator) interfere with the participant's ability to rate the
neuropathy pain.
4. Any amputation of the lower limb which interferes with the participant's ability to
rate the neuropathy pain. If there is any amputation please contact the MM.
5. The presence of any current foot ulcer.
6. Significant peripheral vascular disease defined as symptoms consistent with
intermittent claudication.
3.1.2. Medication/Treatment Exclusion Criteria
7. Use of other investigational drugs within 3 months before screening and throughout the
study.
8. Known or suspected hypersensitivity to all of the assets (active component and
excipients) currently being tested in the Platform Protocol.
9. Undergone neurolytic or neurosurgical therapy or used an implanted neurostimulating
device for neuropathic pain in the distal lower limbs within 3 months of screening.
10. Use of the high dose capsaicin patch (8%) in the 6 months before screening and
throughout the study (for the treatment of PDPN). Use of the capsaicin patch in a
manner that is not expected to interfere with the measurement of PDPN severity is
allowed.
11. Participants who receive and are unwilling to discontinue episodic or periodic
treatments for pain in the distal legs and/or feet (e.g., injections of local
anesthetics) will be excluded. Non-pharmacological pain treatment (e.g.
relaxation/hypnosis, physical or occupational therapy, any exercise-based therapy, any
talk-based therapy, acupuncture, TENS) for the treatment of conditions other than PDPN
is allowed. If the treatment is for PDPN it is allowed if it has been stable for at
least 4 weeks prior to screening and is expected to remain stable throughout the
study.
12. Active use of opioids or marijuana for any reason at screening and unwilling or unable
to discontinue use.
3.1.3. Medical Exclusion Criteria
13. Clinically significant ECG or laboratory abnormalities at the Screening Visit that
would put the participant at undue risk or affect the ability of the participant to
participate in the trial (in the opinion of the investigator). Screening ECG and lab
results may be repeated without requiring a rescreen, as long as the participant is
still within the screening window.
14. Participants whose glycemic control has been unstable within 3 months before screening
(e.g. ketoacidosis requiring hospitalization, any recent episode of hypoglycemia
requiring assistance through medical intervention).
15. Proliferative retinopathy or maculopathy requiring acute treatment.
16. Requiring dialysis.
17. Myocardial infarction or stroke in the past 6 months.
18. Known diagnosis of moderate to severe hepatic impairment (equivalent to Child-Pugh
class B or C) OR aspartate aminotransferase or alanine aminotransferase ≥ 3 times the
upper limit of normal.
19. A clinically significant illness or operative procedure within 4 weeks of screening.
20. Clinically significant surgery planned during the study period. If a surgery is
planned, please contact the MM.
21. History of or currently active malignancy or other medical condition that would put
the participant at undue risk or affect the ability of the participant to participate
in the trial (in the opinion of the investigator).
22. Pregnant or nursing (lactating) women. 3.1.4. Psychosocial and Substance Use Disorders
Exclusion Criteria
23. A clinically significant psychiatric disease that would put the participant at undue
risk or affect the ability of the participant to participate in the trial (in the
opinion of the investigator).
24. Alcohol use disorder or other substance use disorders (other than nicotine or
caffeine) in accordance with DSM-5 criteria within 12 months of screening.
25. Positive urine drug tests defined as follows:
1. Two positive urine drug tests for prescription opioids or marijuana, prior to the
initiation of investigational product (IP); or
2. One positive urine drug test for any illegal drugs (other than marijuana) prior
to the initiation of IP.
26. Vulnerable persons defined as either of the following:
1. Individuals whose willingness to volunteer in a clinical study may be unduly
influenced by the expectation, whether justified or not, of benefits associated
with participation or of a retaliatory response from senior members of a
hierarchy in case of refusal to participate.
2. Individuals whose judgment has been impaired by their physical, mental, or
socio-economical condition and those incapable of giving informed consent.
A Phase 1 in Patients With HLA-A*0201+ and WT1+ Recurrent/Metastatic Cancers
This is a Phase 1, open-label, 2-part, multi-center study evaluating the safety,
tolerability, PK, pharmacodynamics (PD), immunogenicity, and antitumor activity of CUE-102
intravenous (IV) monotherapy in HLA-A*0201 positive patients with WT1 positive
recurrent/metastatic solid tumors who have failed conventional therapies.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05360680
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Inclusion Criteria:
1. Ability to provide informed consent and documentation of informed consent prior to
initiation of any study-related tests or procedures that are not part of standard of
care for the patient's disease.
2. Age ≥18 years old
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Life expectancy ≥12 weeks
5. Measurable disease as per RECIST 1.1 and documented by CT and/or MRI.
6. All tumors must have histologically or cytologically confirmed cancer diagnosis
7. Patients must have any of the following cancers to be eligible:
A. Colorectal cancer
1. Histologically or cytologically documented adenocarcinoma of colon or rectum at
the time of initial presentation
2. Metastatic or locally advanced/unresectable disease
3. Documented disease progression after the last administration of standard
therapies or intolerance to at least 2 prior systemic treatment regimens (CUE-102
will be 3rd line therapy or greater).
B. Gastric cancer (including gastroesophageal junction)
1. Histologically or cytologically documented gastric cancer at the time of initial
presentation
2. Metastatic or locally advanced/unresectable disease
3. Documented disease progression after last administration of standard therapies or
intolerance to standard therapies. (CUE-102 will be 2nd line therapy or greater).
C. Pancreatic cancer
1. Histologically or cytologically documented pancreatic adenocarcinoma at the time
of initial presentation
2. Patients with metastatic or locally advanced/unresectable disease.
3. Prior systemic treatment must include either a fluoropyrimidine-based or
gemcitabine-based regimen in either the (neo)adjuvant or relapsed setting.
(CUE-102 will be 2nd line therapy or greater).
D. Ovarian cancer
1. Histologically or cytologically documented ovarian cancer at the time of initial
presentation
2. Metastatic or locally advanced/unresectable disease, with documented disease
progression after last administration of standard therapies or intolerance to
standard therapies.
3. Prior systemic treatment must include a platinum-based regimen. (CUE-102 will be
2nd line therapy or greater).
4. For patients determined to have platinum-sensitive disease, treatment with a
second platinum-based combination regimen +/- bevacizumab should be considered
prior to treatment with CUE-102 (CUE-102 will be 3rd line therapy or greater).
8. Patient must have HLA-A*0201 genotype as determined by genomic testing.
9. Patient must have histologically and/or cytologically proven tumor(s) that is WT1
positive.
10. Acceptable laboratory parameters.
11. Female patients of childbearing potential must agree to use acceptable contraceptive
measures from the time of main study consent through 90 days after discontinuation of
study drug administration.
12. Non-vasectomized male patients with partners of childbearing potential must use
barrier contraception from the time of main study consent through 90 days after
discontinuation of study drug.
13. Patients who have previously received an immune CPI (e.g., anti-programmed cell death
ligand 1 (anti PD-L1), anti-programmed cell death 1 (anti-PD-1), anti-cytotoxic T
lymphocyte-associated antigen 4 [CTLA-4]) prior to enrollment must have toxicities
related to the CPI resolved to CTCAE ≤ Grade 1 or baseline (level prior to the CPI) to
be eligible for enrollment. Patients who have experienced CPI-related endocrinopathies
(e.g., diabetes, adrenal insufficiency) may participate if endocrinopathies are
controlled (CTCAE ≤ Grade 1) with endocrinology support and appropriate repletion.
Note: Patients who experienced previous hypothyroidism toxicity on a CPI are eligible
to enter study regardless of CTCAE grade resolution as long as the patient is well
controlled on thyroid replacement hormone.
Exclusion Criteria:
1. Female patients who are pregnant or plan to become pregnant during the course of the
trial
2. Female patients who are breastfeeding
3. Patients with symptomatic central nervous system (CNS) metastases must have been
treated, be asymptomatic, and not have any of the following at the time of enrollment:
1. Need for concurrent treatment for the CNS disease (e.g., surgery, radiation,
corticosteroids >10 mg prednisone/day or equivalent)
2. Progression of CNS metastases on CT or MRI for at least 28 days after last day of
prior therapy for the CNS metastases
3. Concurrent leptomeningeal disease or cord compression.
4. Has an active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form
of systemic treatment and is permitted.
5. History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation
6. Treatment with any systemic anti-neoplastic therapy, or investigational therapy within
the 14 days (or 28 days, for antibody drugs), before the first dose of CUE-102.
7. Treatment with radiation therapy within 14 days before the first dose of CUE-102
8. Treatment with corticosteroids (> 10 mg per day prednisone or equivalent) or other
immune suppressive drugs within 14 days before the first dose of CUE-102. Steroids for
topical, ophthalmic, inhaled, or nasal administration are permitted. Physiological
replacement with up to a maximum dose of 5 mg equivalence of prednisone per day is
permitted.
9. History of clinically significant cardiovascular disease
10. Clinically significant pulmonary compromise (e.g., requirement for supplemental
oxygen)
11. Clinically significant gastrointestinal (GI) disorders
12. Patients who experienced the following immune CPI-related AEs are ineligible even if
the AE resolved to ≤ Grade 1 or baseline:
1. ≥ Grade 3 ocular AE
2. Changes in liver function tests that met the criteria for Hy's Law (> 3× ULN of
either ALT/AST with concurrent > 2× ULN of total bilirubin (total and direct) and
without alternate etiology)
3. ≥ Grade 3 neurologic toxicity
4. ≥ Grade 3 colitis
5. ≥ Grade 3 renal toxicity
13. Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral
treatment within 7 days before the first dose of CUE-102.
14. No known history of infection or positive test for HIV, Hepatitis B or Hepatitis C,
testing prior to enrollment is not required unless mandated by local authority
15. Second primary invasive malignancy that has not been in remission for > 2 years.
16. History of trauma or major surgery within 28 days before the first dose of CUE-102
17. Any serious underlying medical or psychiatric condition that would impair the ability
of the patient to receive or tolerate the planned treatment at the investigational
site
18. Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient
contained in the drug formulation for CUE-102
19. Vaccination with any live virus vaccine within 28 days before the first dose of
CUE-102. Inactivated annual influenza vaccination is allowed.
20. Dementia or altered mental status that would preclude understanding and rendering of
informed consent
21. Active or history of significant alcohol or other substance abuse within 1 year before
the first dose of CUE-102
Colorectal Cancer, Gastric Cancer, Pancreatic Cancer, Ovarian Cancer, Esophagus, Stomach, Colon, Pancreas, Other Digestive Organ, Ovary, Colon and Rectum, Gastrointestinal cancers, other
A Study of Tazemetostat With Rituximab and Abbreviated Bendamustine in the Frontline Treatment of High Tumor Burden Follicular Lymphoma
This study is planned as a single arm clinical trial of tazemetostat in combination with
bendamustine and rituximab with both a phase I and phase II component. All patients will
receive tazemetostat twice daily on days 1-28 in combination with bendamustine 90 mg/m2 IV on
days 1 and 2 and rituximab 375 mg/m2 IV on day 1 of a 28-day cycle for up to three cycles.
Following this, patients will receive tazemetostat twice daily on days 1-28 and rituximab 375
mg/m2 IV on day 1 of a 28-day cycle for up to three cycles.
Vaishalee Kenkre, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05551936
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Inclusion Criteria:
• Written informed consent and HIPAA authorization for release of personal health
information. NOTE: HIPAA authorization may be included in the informed consent or
obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-2 within 10 days prior to registration.
• Low grade follicular lymphoma (grade 1-2 or 3A by WHO-HAEM4R and/or cFL by WHO-HAEM5).
Specifically, grade 3B or FLBL will not be allowed. Must not have evidence of
transformed lymphoma at the time of study enrollment.
• Stage II, III, or IV by Ann Arbor staging system.
• Meet the definition of high tumor burden follicular lymphoma as defined by Groupe
d'Etude des Lymphomes Follicularies (GELF) Criteria or be defined as high risk by the
follicular lymphoma international prognostic index (FLIPI) 1 or FLIPI 2.
--GELF Criteria (Must meet ≥ 1 of the following)
• Any nodal or extranodal mass ≥ 7 cm in diameter
• Involvement of ≥ 3 nodal sites ≥ 3 cm
• Systemic or B symptoms
• Presence of serous effusion
• Splenic enlargement
• Risk of compression syndrome (epidural, ureteral, etc)
• Leukemic phase of disease
• Cytopenia deemed due to disease involvement (hemoglobin < 10, granulocyte count <
1.5×10^9/L, or platelet count < 100×10^9/L)
• In addition to meeting GELF criteria, must have at least one FDG-avid site on PET that
measures 1.5 cm in at least one dimension of a nodal site or 1cm in at least one
dimension for extranodal sites.
• Received no prior therapy except local radiation therapy (field did not exceed 2
adjacent nodal regions), single agent rituximab (limited to 4 doses), or steroids for
symptom control in the 28 days preceding trial enrollment.
• Must have prior EZH2 testing already performed or have tissue available to perform
retrospective EZH2 testing. If prior EZH2 results are not available, tissue must be
submitted. Tissue block is preferred but unstained slides are also acceptable.
Patients who have insufficient or suboptimal tissue must be willing to have a biopsy
performed prior to starting study drugs. See Correlative Lab Manual for details.
• Demonstrate adequate organ function as defined below; all screening labs to be
obtained within 28 days prior to registration.
• Hematological
• Platelets ≥ 50 K/dL
• Absolute Neutrophil Count (ANC) ≥ 1000 K/mm3
• Hemoglobin (Hgb) ≥ 8 g/dL
• Renal
• Calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault
formula
• or Serum creatinine < 2 mg/dL
• Hepatic
• Bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 3 × ULN
• Alanine aminotransferase (ALT) ≤ 3 × ULN
• Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT)
Activated Partial Thromboplastin Time (aPTT) ≤ 2 × ULN
• Females of childbearing potential with a male partner able to father a child must have
a negative serum or urine pregnancy test within 7 days prior to registration. See the
protocol for definition of childbearing potential.
• Females of childbearing potential must be willing to abstain from vaginal intercourse
or use an effective method(s) of contraception from the time of informed consent,
during the study and for 6 months after the last dose of study drug(s). Males able to
father a child must be willing to abstain from vaginal intercourse or to use an
effective method(s) of contraception from initiation of treatment, during the study
and for 3 months after the last dose of study drug(s). See the protocol.
• As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study.
Exclusion Criteria:
• Active infection requiring systemic therapy with 4 weeks of study drug administration.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study).
• Concurrent malignancy or malignancy within the last 3 years (except for ductal breast
cancer in situ, non-melanoma skin cancer, prostate cancer not requiring treatment, and
cervical carcinoma in situ) whose natural history or treatment has the potential to
interfere with the safety or efficacy assessment of the investigational regimen are
not eligible for this trial.
• Active central nervous system (CNS) metastases or leptomeningeal disease. NOTE:
Subjects who are symptomatic and have not undergone prior brain imaging must undergo a
head computed tomography (CT) scan or brain MRI within 28 days prior to registration
to exclude brain metastases.
• Treatment with any investigational drug within 4 weeks prior to registration.
• Subjects who require chronic use of moderate or strong CYP3A4/5 inhibitors or inducers
within 28 days prior to registration.
• Clinically significant acute infection requiring systemic antibacterial, antifungal,
or antiviral therapy.
• Known Uncontrolled Human Immunodeficiency Virus infection. Testing not required. NOTE:
If a subject is known to have HIV/AIDS, then they will be allowed on study with
adequate antiviral therapy, no detectable viral load, and stable on antiviral
treatment for ≥ 4 weeks prior to first dose of study drug(s).
• Known hepatitis C infection. Testing not required. NOTE: If hepatitis C antibody test
is known positive, patients are excluded unless a hepatitis C virus ribonucleic acid
(HCV RNA) is negative.
• Must be tested for hepatitis B within 28 days of registration: including hepatitis B
surface antigen, hepatitis B surface antibody, hepatitis B core antibody. A positive
hepatitis B core antibody should be followed by hepatitis B DNA PCR testing to confirm
or rule out active infection. Patients with hepatitis B surface antigen and/or
detectable hepatitis B DNA PCR are not allowed on study. Patients with a positive
hepatitis B core antibody but negative hepatitis B surface antigen and hepatitis B DNA
PCR will be allowed on study, but hepatitis B prophylactic treatment should be
strongly considered.
• Clinically significant cardiovascular disease or cardiac insufficiency (New York Heart
Association classes III-IV), cardiomyopathy, preexisting clinically significant
arrhythmia, acute myocardial infarction within 3 months of enrollment, angina pectoris
within 3 months of enrollment.
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
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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
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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
Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors
IMC-F106C is an immune-mobilizing monoclonal T cell receptor against cancer (ImmTAC ®)
designed for the treatment of cancers positive for the tumor-associated antigen PRAME. This
is a first-in-human trial designed to evaluate the safety and efficacy of IMC-F106C in adult
patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for
PRAME.
Vincent Ma, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04262466
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. ECOG PS 0 or 1
2. HLA-A*02:01 positive
3. PRAME positive tumor
4. Relapsed from, refractory to, or intolerant of standard therapies; or, in combination
with standard therapies
5. If applicable, must agree to use highly effective contraception
Exclusion Criteria:
1. Symptomatic or untreated central nervous system metastasis
2. Recent bowel obstruction
3. Ongoing ascites or effusion requiring recent drainages
4. Significant immune-mediated adverse event with prior immunotherapy (patients in
checkpoint inhibitor combination treatment)
5. Inadequate washout from prior anticancer therapy
6. Significant ongoing toxicity from prior anticancer treatment
7. Out-of-range laboratory values
8. Clinically significant lung, heart, or autoimmune disease
9. Ongoing requirement for immunosuppressive treatment
10. Prior solid organ or bone marrow transplant
11. Active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency
virus (HIV) infection
12. Significant secondary malignancy
13. Hypersensitivity to study drug or excipients
14. Antibiotics, vaccines or surgery within 2-4 weeks prior to the first dose of study
intervention
15. Pregnant or lactating
16. Any other contraindication for applicable combination partner based on local
prescribing information
A Prospective Registry Study to Assess Real-world Patient Characteristics, Treatment Patterns, and Longitudinal Outcomes in Patients Receiving Mavacamten and Other Treatments for Symptomatic Obstructive Hypertrophic Cardiomyopathy (Obstructive HCM) (DISCOVER-HCM)
The purpose of this study is to evaluate the safety of mavacamten in patients with
symptomatic obstructive hypertrophic cardiomyopathy (HCM) treated in the real-world setting.
The registry study also provide a real-world understanding of the current obstructive HCM
patient population, treatment patterns, and clinical relevant outcomes for patients with
symptomatic obstructive HCM in the US.
Aurangzeb Baber
All
18 Years and over
IV
This study is NOT accepting healthy volunteers
NCT05489705
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Willing and able to provide written informed consent form (ICF) and any required
privacy authorization prior to the initiation of study procedures. i. Diagnosis of
obstructive HCM consistent with 2020 American Heart Association/American College of
Cardiology (AHA/ACC) guidelines. ii. Obstructive HCM is defined clinically by the
presence of increased LV wall thickness ≥ 15 mm (or ≥ 13 mm with positive family
history of HCM) in a nondilated ventricular chamber that is not solely explained by
abnormal loading conditions (eg, another cardiac or systemic disease) and peak LVOT
gradient of
≥ 30 mmHg at rest or with provocation.
2. Has documented LVEF of ≥ 55% recorded by echocardiography within the last 6 months.
3. Symptoms consistent with NYHA functional class II-IV.
4. ≥ 18 years of age at the time of informed consent.
5. Receiving BBs, non-dihydropyridine calcium. channel blockers (non-DHP CCBs),
disopyramide, and/or mavacamten (once available) as part of routine clinical care; or
currently receiving no treatment due to intolerance or failure of prior treatment (eg,
BBs, non-DHP CCBs, or disopyramide) for obstructive HCM.
Exclusion Criteria:
1. Known phenocopy disease (eg, Fabry disease, amyloidosis) or LV hypertrophy associated
with hypertension.
2. Documentation of any fixed obstruction of the outflow tract such as aortic valve
stenosis or replacement.
3. Prior treatment of obstructive HCM with invasive septal reduction (surgical myectomy
or percutaneous alcohol septal ablation [ASA]) within 6 months prior to enrollment;
participants with an unsuccessful myectomy or percutaneous ASA performed > 6 months
prior to enrollment may be enrolled.
4. Naïve to treatment for obstructive HCM (ie, never treated with BBs, non-DHP CCBs, or
disopyramide).
5. Receiving an investigational therapeutic agent for obstructive HCM (eg,
myosin-inhibitors other than mavacamten) in an interventional clinical trial at
participant enrollment.
6. Previously or currently enrolled in a long-term safety extension study of mavacamten
(eg, EXPLORER-HCM [ClinicalTrials.gov, NCT03470545], MAVA-LTE [NCT03723655],
PIONEER-OLE [NCT03496168], VALORHCM [NCT04349072], or MAVERICK [NCT03442764])
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
Show full eligibility criteria
Hide eligibility criteria
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
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, Malignant Solid Neoplasm
The objective of the OrganOx metra® New Enrollment Post-Approval Study is to collect data on
the post-transplant clinical outcomes of DBD and DCD donor livers preserved and assessed on
the OrganOx according to the current indications for use in the real-world setting.
David Al-Adra, MD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT05526326
Show full eligibility criteria
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Inclusion Criteria:
• Subject is 18 years of age or greater
• Subject is registered as an active recipient on the UNOS waiting list for liver
transplantation
• Subject, or legally authorized representative, is able and willing to give informed
consent and HIPAA authorization
• Subject is able and willing to comply with all study requirements (in the opinion of
the Investigator)
Exclusion Criteria:
• Subject requiring all of the following at the time of transplantation:
1. Oxygen therapy via a ventilator/respirator
2. Inotropic support
3. Renal replacement therapy
• Subject has acute/fulminant liver failure (UNOS status 1A)
• Subject planned to undergo simultaneous transplantation of more than one organ (e.g.,
liver and kidney) from the same liver donor
• Subject is pregnant (as confirmed by urine or serum pregnancy test) or nursing
• Concurrent enrollment in another clinical study. Subjects enrolled in clinical studies
or registries where only measurements and/or samples are taken (no test device or test
drug) are allowed to participate.
Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Based on PET Imaging
This phase III trial tests two questions by two separate comparisons of therapies. The first
question is whether enhanced therapy (apalutamide in combination with abiraterone +
prednisone) added to standard of care (prostate radiation therapy and short term androgen
deprivation) is more effective compared to standard of care alone in patients with prostate
cancer who experience biochemical recurrence (a rise in the blood level of prostate specific
antigen [PSA] after surgical removal of the prostate cancer).
A second question tests treatment in patients with biochemical recurrence who show prostate
cancer spreading outside the pelvis (metastasis) by positron emission tomography (PET)
imaging. In these patients, the benefit of adding metastasis-directed radiation to enhanced
therapy (apalutamide in combination with abiraterone + prednisone) is tested.
Diagnostic procedures, such as PET, may help doctors look for cancer that has spread to the
pelvis. Androgens are hormones that may cause the growth of prostate cancer cells.
Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor
cells. Metastasis-directed targeted radiation therapy uses high energy rays to kill tumor
cells and shrink tumors that have spread. This trial may help doctors determine if using PET
results to deliver more tailored treatment (i.e., adding apalutamide, with or without
targeted radiation therapy, to standard of care treatment) works better than standard of care
treatment alone in patients with biochemical recurrence of prostate cancer.
John Floberg, Assistant Professor
Male
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04423211
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• STEP 0: REGISTRATION ELIGIBILITY CRITERIA
• Patient must be male and >= 18 years of age.
• Patient must have had a radical prostatectomy (RP) as definitive therapy for
histopathologically-proven prostatic adenocarcinoma
• Patient must have biochemical recurrence (BCR) after RP, defined as follows:
• If time to BCR, defined as time to first detectable PSA ( > lower limit of normal
for assay used) after RP, is < 12 months, a minimum PSA level of >= 0.2 ng/mL and
a confirmatory reading of >= 0.2 ng/mL is required, per the American Urological
Association (AUA) definition (Note: patients with a persistent PSA reading of at
least 0.2 ng/mL are eligible)
• If time to BCR, defined as time to first detectable PSA (> lower limit of normal
for assay used) after RP, is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is
required
• If the patient has a detectable PSA (> lower limit of normal for assay used) at
any time after RP AND has an eligible baseline SOC PET (PET1) with at least one
positive lesion in any location, then there is no minimum PSA requirement
• Patients must have no definite evidence for extrapelvic metastatic disease by
conventional imaging modalities (CIM) (CT abdomen/pelvis or MRI abdomen/pelvis AND
bone scintigraphy, or equivalent), within 26 weeks prior to Step 0 registration. If a
patient only has a study-eligible PET/CT or PET/MR (i.e., PET done without prior CIM):
if the PET is negative for extrapelvic lesions, then baseline CIM is NOT required. If
the PET positive for extrapelvic lesions, then patient should have a baseline CT/MRI
for soft tissue lesions and/or a bone scan for osseous lesions
• Study eligible = PET using FDA-approved radiotracer and performed within 16 weeks
prior to study registration
• Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic
soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to
common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT
fields. Baseline PET/CT or PET/MR scan (PET1) is eligible for this study if the SOC
PET scan is completed with an FDA approved radiotracer for prostate cancer after Step
0 registration and prior to Step 1 randomization OR up to 16 weeks prior to Step 0
registration
• Patient must be a candidate for SOC post-prostatectomy radiation therapy (RT) to the
prostate bed and pelvic nodes with androgen deprivation therapy (ADT)
• Patient must have the ability to understand and the willingness to sign a written
informed consent document. Patients with impaired decision-making capacity (IDMC) who
have a legally authorized representative (LAR) or caregiver and/or family member
available will also be considered eligible
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient must not have started ADT for biochemical recurrence prior to baseline PET
(PET1) imaging. A short course of low-dose anti-androgen such as bicalutamide, given
after baseline study PET/CT but prior to study registration, is permitted as a brief
temporizing measure in advance of starting protocol-approved SOC ADT.
• Patient must not be enrolled in another therapeutic clinical trial
• Patient must be able to lie flat and still for approximately 20-30 minutes or
otherwise tolerate a PET scan and radiation treatment planning and delivery
• Patients undergoing a PET/MR must meet local institutional safety guidelines for MRI
• Patient must not have history of seizures or known condition that may cause
predisposal to seizures (e.g., stroke or head trauma resulting in loss of
consciousness) within 1 year prior to registration
• Patient must not have history of inflammatory bowel disease or any gastrointestinal
disorder affecting absorption that is expected to increase risk of complication from
radiotherapy
• Hemoglobin (Hgb) >= 9.0 g/dL (independent of transfusion and/or growth factors within
3 months prior to Step 0 registration) (obtained within 8 weeks prior to Step 0
registration)
• Leukocytes >= 3,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Absolute neutrophil count >= 1,500/mcL (obtained within 8 weeks prior to Step 0
registration)
• Platelets >= 100,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (patients with
Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, must have a direct bilirubin of
< 1.5 x ULN to be eligible) (obtained within 8 weeks prior to Step 0 registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN (obtained within 8 weeks prior to Step 0 registration)
• Creatine < 1.5 x instituional ULN (or measured creatinine clearance > 30 mL/min)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class I or II (by patient symptoms) or A
or B (by objective assessment)
• Patient must not have completed a course of prior pelvic radiation therapy for any
reason
• Patient must agree not to father children while on study
• Patient must be English or Spanish speaking to be eligible for the QOL component of
the study
• NOTE: Sites cannot translate the associated QOL forms
• STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
• Patient must have completed a baseline SOC PET/CT or PET/MR (PET1 scan) using FDA
approved radiotracer with results of extra-pelvic metastases involvement known
(positive or negative). The PET1 must have been completed after Step 0 registration
and prior to Step 1 randomization OR up to 12 weeks prior to Step 0 registration
• For patients with negative extra-pelvic metastases, PET-imaging status of intra-pelvic
nodes must be known (positive or negative)
• For patients with positive extra-pelvic metastases (defined as any PET positive
lesions outside of standard salvage RT fields [prostate bed +/- typical whole
pelvis]), the number of extra-pelvic lesions must be known (1 •5 or > 5 extra-pelvic
lesions)
A Study Evaluating the Long-term Safety and Efficacy of VX-121 Combination Therapy
The purpose of this study is to evaluate the long-term safety, tolerability, and efficacy of
VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in participants with cystic fibrosis.
Andrew Braun
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05444257
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Key
Inclusion Criteria:
• Completed study drug treatment in a parent study VX20-121-102 (NCT05033080) and
VX20-121-103 (NCT05076149); or had study drug interruption(s) in a parent study but
did not permanently discontinue study drug, and completed study visits up to the last
scheduled visit of the Treatment Period in the parent study
Key
Exclusion Criteria:
• History of drug intolerance in a parent study
• Pregnant or breast-feeding females
Other protocol defined Inclusion/Exclusion criteria may apply.
BIVV020 (SAR445088) n Prevention and Treatment of Antibody-mediated Rejection (AMR)
Primary Objectives:
- Cohort A: To evaluate the efficacy of BIVV020 in prevention of AMR
- Cohort B: To evaluate the efficacy of BIVV020 in treatment of active AMR
Secondary Objectives:
- To assess the overall efficacy of BIVV020 in prevention or treatment of AMR
- To characterize the safety and tolerability of BIVV020 in kidney transplant participants
- To characterize the pharmacokinetic (PK) profile of BIVV020 in kidney transplant
participants
- To evaluate the immunogenicity of BIVV020
Fahad Aziz
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05156710
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Inclusion Criteria:
-Participant intended to receive SOC therapy per Investigator's judgment and local
practice.
Cohort A: Participants with chronic kidney disease who will receive a kidney transplant
from a living or deceased donor.
Cohort B: Participants who are kidney transplant recipients diagnosed with active AMR.
• BMI ≤ 40 kg/m2.
• Contraceptive use by women during the treatment period, and for at least 49 weeks
after the last administration of IMP (BIVV020 + SOC arm participant) or last treatment
period visit (SOC arm participant).
• Contraceptive use by men during the treatment period, and for at least 49 weeks after
the last administration of IMP (BIVV020 + SOC arm participant) or last treatment
period visit (SOC arm participant).
Exclusion Criteria:
• Participants who are ABO incompatible with their donors.
• Participants with known active ongoing infection as per below:
1. Positive HIV.
2. Positive HBV.
3. HCV with detectable HCV RNA.
4. Within 4 weeks of first study intervention: any serious infection, or any active
bacterial infection, or any other infection which is clinically significant in
the option of the Investigator, unless it can be confirmed that infection was
cleared at least 3 days prior to first study intervention.
• History of active tuberculosis (TB) regardless of treatment.
• Participants with clinical diagnosis of systemic lupus erythematosus (SLE).
• Prior treatment with complement system inhibitor within 5 times the half-life.
• Current enrollment in any other clinical study where the last investigational study
treatment administration was within 5 half-lives from study intervention initiation.
The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.
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
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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
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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
Colon Adjuvant Chemotherapy Based on Evaluation of Residual Disease (CIRCULATE-US)
This Phase II/III trial will evaluate the what kind of chemotherapy to recommend to patients
based on the presence or absences of circulating tumor DNA (ctDNA) after surgery for colon
cancer.
Dustin Deming, MD
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT05174169
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Inclusion Criteria:
The patient must have an ECOG performance status of 0 or 1.
Patients must have histologically/pathologically confirmed colon adenocarcinoma (T1-3,
N1/N1c) with R0 resection accordingly to AJCC 8th edition criteria. NOTE: Patients with
pathologic stages II or IIIC colon adenocarcinoma with R0 resection who have a commercially
obtained Signatera™ ctDNA+ve assay result post-operatively meeting all timelines and
eligibility requirements otherwise, are eligible for enrollment and inclusion in Cohort B.
No radiographic evidence of overt metastatic disease within 28 days prior to study entry
(CT with IV contrast or MRI imaging is acceptable and must include chest, abdomen, and
pelvis).
The distal extent of the tumor must be greater than or equal to 12 cm from the anal verge
on colonoscopy or above the peritoneal reflection as documented during surgery or on
pathology specimen (i.e., excluding rectal adenocarcinomas warranting treatment with
chemoradiation).
The patient must have had an en bloc complete gross resection of tumor (curative
resection). Patients who have had a two-stage surgical procedure, to first provide a
decompressive colostomy and then in a later procedure to have the definitive surgical
resection, are eligible.
The resected tumor specimen and a blood specimen from patients with Stage IIIA or Stage
IIIB colon cancer must have central testing for ctDNA using the Signatera™ assay by Natera.
NOTE: Patients with stage IIIA or IIIB colon cancer who otherwise meet eligibility criteria
and have had ctDNA status checked with the Signatera™ assay as routine care outside of the
study, are allowed to be enrolled, and will be retested and placed in either Cohort A or
Cohort B depending on the central ctDNA testing result.
NOTE: Patients with stage II or IIIC colon cancer who otherwise meet eligibility criteria
and have had ctDNA status checked with the Signatera™ assay as routine care outside of the
study AND have a ctDNA+ve result, are allowed to be enrolled. Patients will have central
ctDNA testing, confirmed to be ctDNA+ve, and placed in Cohort B.
Tumor must be documented as microsatellite stable or have intact mismatch repair proteins
through CLIA-approved laboratory testing. Patients whose tumors are MSI-H or dMMR are
excluded.
The treating investigator must deem the patient a candidate for all potential agents used
in this trial (5FU, LV, oxaliplatin and irinotecan).
The interval between surgery (post-operative Day 7) and study entry must be no more than 60
days.
Availability and provision of adequate surgical tumor tissue for molecular diagnostics and
confirmatory profiling.
Adequate hematologic function within 28 days before study entry defined as follows:
• Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
• Platelet count must be greater than or equal to 100,000/mm3; and
• Hemoglobin must be greater than or equal to 9 g/dL.
Adequate hepatic function within 28 days before study entry defined as follows:
• total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab
and
• alkaline phosphatase must be less than 2.5 x ULN for the lab; and
• AST and ALT must be less than 2.5 x ULN for the lab.
Adequate renal function within 28 days before study entry defined as serum creatinine less
than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance
greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with
creatinine levels greater than 1.5 x ULN for the lab.
For Women Creatinine Clearance (mL/min) = (140 •age) x weight (kg) x 0.85 72 x serum
creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 •age) x weight (kg) 72 x
serum creatinine (mg/dL)
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load
within 6 months are eligible for this trial.
Pregnancy test (urine or serum according to institutional standard) done within 14 days
before study entry must be negative (for women of childbearing potential only).
Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of
INR if they are randomized to Arm 1 or Arm 3 and receive capecitabine.
Eligibility Criteria for Cohort A Arm-2 patients on Second Randomization
Patient must have developed a ctDNA +ve assay during serial monitoring.
Patient's willingness to be re-randomized affirmed.
The patient must continue to have an ECOG performance status of 0 or 1.
No radiographic evidence of overt metastatic disease.
Pregnancy test (urine or serum according to institutional standard) done within 14 days
before study entry must be negative (for women of childbearing potential only).
Adequate hematologic function within 28 days before randomization defined as follows:
• Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
• Platelet count must be greater than or equal to 100,000/mm3; and
• Hemoglobin must be greater than or equal to 9 g/dL.
Adequate hepatic function within 28 days before randomization defined as follows:
• total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab
and
• alkaline phosphatase must be less than 2.5 x ULN for the lab; and
• AST and ALT must be less than 2.5 x ULN for the lab.
Adequate renal function within 28 days before randomization defined as serum creatinine
less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance
greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with
creatinine levels greater than 1.5 x ULN for the lab.
For Women Creatinine Clearance (mL/min) = (140 •age) x weight (kg) x 0.85 72 x serum
creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 •age) x weight (kg) 72 x
serum creatinine (mg/dL)
Exclusion Criteria:
Colon cancer histology other than adenocarcinoma (i.e., neuroendocrine carcinoma, sarcoma,
lymphoma, squamous cell carcinoma, etc.).
Pathologic, clinical, or radiologic overt evidence of metastatic disease. This includes
isolated, distant, or non-contiguous intra-abdominal metastases, even if resected.
Tumor-related bowel perforation.
History of prior invasive colon malignancy, regardless of disease-free interval.
History of bone marrow or solid organ transplantation (regardless of current
immunosuppressive therapy needs). Bone grafts, skin grafts, corneal transplants and
organ/tissue donation are not exclusionary.
Any prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy
administered as treatment for colorectal cancer (e.g., primary colon adenocarcinomas for
which treatment with neoadjuvant chemotherapy and/or radiation is warranted are not
permitted).
Other invasive malignancy within 5 years before study entry. Exceptions are colonic polyps,
non-melanoma skin cancer or any carcinoma-in-situ.
Synchronous primary rectal and/ or colon cancers.
Patients with known history or current symptoms of cardiac disease, or history of treatment
with cardiotoxic agents, should have a clinical risk assessment of cardiac function using
the New York Heart Association Functional Classification. To be eligible for this trial,
patients should be class 2B or better.
Sensory or motor neuropathy greater than or equal to grade 2, according to CTCAE v5.0.
Blood transfusion within two weeks before collection of blood for central ctDNA testing.
Active seizure disorder uncontrolled by medication.
Active or chronic infection requiring systemic therapy.
Known homozygous DPD (dihydropyrimidine dehydrogenase) deficiency.
Patients known to have Gilbert's Syndrome or homozygosity for UGT1A1*28 polymorphism.
Pregnancy or lactation at the time of study entry.
Co-morbid illnesses or other concurrent disease that would make the patient inappropriate
for entry into this study (i.e., unable to tolerate 6 months of combination chemotherapy or
interfere significantly with the proper assessment of safety and toxicity of the prescribed
regimens or prevent required follow-up).
Ineligibility Criteria for Cohort A Arm-2 patients on Second Randomization
Pregnancy or lactation at the time of randomization.
No longer a candidate for systemic chemotherapy (FOLFOX, CAPOX, and mFOLFIRINOX) in the
opinion of the treating investigator.
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
Study to Assess Batoclimab in Participants With Active Thyroid Eye Disease
To evaluate the efficacy of batoclimab 680 milligrams (mg) subcutaneous (SC) once a week (QW)
for 12 weeks followed by 340 mg SC QW for 12 weeks versus placebo on proptosis responder rate
at Week 24.
Suzanne Van Landingham
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05517421
Show full eligibility criteria
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Inclusion criteria:
• Are ≥18 years of age at screening.
• Have a clinical diagnosis of TED associated with active, moderate to severe TED with
the following at screening and Visit 0:
• A CAS ≥ 4 in either eye, and
• Clinical evidence of worsened proptosis with:
1. Proptosis ≥ 18 mm and/or
2. Proptosis ≥ 3 mm increase from participant's baseline (prior to diagnosis of
TED), as estimated by the Investigator/assessor
• Have moderate to severe active TED, as defined by European Group on Graves'
Orbitopathy (EUGOGO) guidelines.
• Have onset of active TED within 12 months prior to screening.
• Have documented evidence of detectable anti-TSHR-Ab at screening.
• Are not expected to require immediate surgical intervention and are not planning
corrective surgery/irradiation or medical therapy for TED during the course of the
study.
• Are euthyroid with the baseline disease under control or have mild hypo- or
hyperthyroidism.
Additional inclusion criteria are defined in the protocol.
Exclusion criteria:
• Have decreased best corrected visual acuity due to optic neuropathy.
• Have at least a 2-point decrease in CAS or ≥2 mm decrease in proptosis between
screening and Baseline assessments in either eye.
• Have used any steroid (intravenous or oral) for the treatment of TED or other
conditions within 4 weeks prior to screening.
• Have used any steroid (Intravenous or oral) with a cumulative dose equivalent to ≥ 1 g
of methylprednisolone for the treatment of TED.
• Have known autoimmune disease other than TED, that, in the opinion of the
Investigator, would interfere with the course and conduct of the study.
• Had previous orbital irradiation or surgery for TED.
Additional exclusion criteria are defined in the protocol.
Comparison of Chemotherapy Before and After Surgery Versus After Surgery Alone for the Treatment of Gallbladder Cancer
This phase II/III trial compares the effect of adding chemotherapy before and after surgery
versus after surgery alone (usual treatment) in treating patients with stage II-III
gallbladder cancer. Chemotherapy drugs, such as gemcitabine and cisplatin, 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. Giving chemotherapy before surgery may make the
tumor smaller; therefore, may reduce the extent of surgery. Additionally, it may make it
easier for the surgeon to distinguish between normal and cancerous tissue. Giving
chemotherapy after surgery may kill any remaining tumor cells. This study will determine
whether giving chemotherapy before surgery increases the length of time before the cancer may
return and whether it will increase a patient's life span compared to the usual approach.
Sam Lubner, MD
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT04559139
Show full eligibility criteria
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Inclusion Criteria:
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0-1
• Patient must have histologically-confirmed T2 or T3 gallbladder cancer discovered
incidentally at the time of or following routine cholecystectomy for presumed benign
disease
• NOTE: Patients with histologically-confirmed Tis, T1a, T1b, or T4 tumors are not
eligible
• Patient must have undergone initial cholecystectomy within 12 weeks prior to
randomization
• Patient must have the ability to understand and the willingness to sign a written
informed consent document
• Leukocytes >= 3,000/mcL (obtained =< 28 days prior to randomization)
• Absolute neutrophil count >= 1,500/mcL (obtained =< 28 days prior to randomization)
• Platelets >= 100,000/mcL (obtained =< 28 days prior to randomization)
• Total bilirubin =< institutional upper limit of normal (ULN) except in patients with
Gilbert's syndrome. Patients with Gilbert's syndrome are eligible if direct bilirubin
< 1.5 x ULN of the direct bilirubin (obtained =< 28 days prior to randomization)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
institutional ULN (obtained =< 28 days prior to randomization)
• Serum creatinine =< institutional ULN OR creatinine clearance >= 50 mL/min/1.73 m^2
(Based on Cockcroft Gault estimation) (obtained =< 28 days prior to randomization)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months of randomization are eligible for
this trial
• 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 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 are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association functional classification. To be
eligible for this trial, patients should be class 2B or better
Exclusion Criteria:
• Patient must not have any evidence of metastatic disease or inoperable loco-regional
disease based on high-quality, preoperative, cross-sectional imaging (computed
tomography [CT] or magnetic resonance imaging [MRI]) of the chest, abdomen, and pelvis
(C/A/P) obtained within 6 weeks prior to randomization, defined as
• No radiographic evidence of distant disease (M1 disease)
• No radiographic evidence of tumor invasion into multiple extrahepatic organs (T4
disease)
• No radiographic evidence of distant lymph node involvement (celiac, para-aortic,
para-caval lymph nodes)
• No evidence of new-onset ascites
• Soft tissue thickening within or in direct communication with the gallbladder
fossa, peri-portal lymph node involvement, involvement of one extrahepatic organ,
and other disease within the confines of what constitutes 'localized resectable'
disease are allowable
• Women must not be pregnant or breast feeding due to the potential harm to unborn fetus
and possible risk for adverse events in nursing infants with the treatment regimens
being used. All females of child bearing potential must have a serum or urine
pregnancy test to rule out pregnancy within 14 days prior to randomization. A female
of childbearing potential is defined as any woman, regardless of sexual orientation or
whether they have undergone tubal ligation, who meets the following criteria: 1) has
achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral
oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer
therapy does not rule out childbearing potential) for at least 24 consecutive months
(i.e., has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential and sexually active males must not expect to conceive
or father children by being strongly advised to use accepted and effective method(s)
of contraception or to abstain from sexual intercourse for the duration of their
participation in the study
Stage II Gallbladder Cancer AJCC v8, Stage IIA Gallbladder Cancer AJCC v8, Stage IIB Gallbladder Cancer AJCC v8, Stage III Gallbladder Cancer AJCC v8, Stage IIIA Gallbladder Cancer AJCC v8, Stage IIIB Gallbladder Cancer AJCC v8, Other Digestive Organ, Gastrointestinal cancers, other
Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Breast Cancers
Patient will be treated with neratinib, an aromatase inhibitor and trastuzumab for 24 weeks
prior to surgery, following an initial 3 weeks of neratinib alone, aromatase inhibitor alone
or the combination of neratinib and an aromatase inhibitor. A breast biopsy will be performed
prior to Day 1 of week 4 of treatment. Following surgery, patients will receive standard of
care HER2-directed and endocrine therapy at the treating physician's discretion.
Kari Wisinski, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04886531
Show full eligibility criteria
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Inclusion Criteria:
Subject must meet all of the following applicable inclusion criteria to participate in this
study:
• Written informed consent and HIPAA authorization for release of personal health
information. NOTE: HIPAA authorization may be included in the informed consent or
obtained separately.
• Age ≥ 18 years at the time of consent.
• Postmenopausal females. NOTE: Postmenopausal status defined as: prior bilateral
oophorectomy, Age ≥ 60 years, or Age < 60 years and amenorrhea for 12 or more months
in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) or an
estradiol level in postmenopausal ranges per local reference range.
• ECOG Performance Status of 0-2 within 28 days prior to registration.
• Anatomic, clinical stage I-III, invasive breast cancer, greater than 10mm
• HER2-positive (by the most recent ASCO-CAP criteria)
• ER positive (≥ 10%). NOTE: There is no requirement for PR status; PR positive or
negative allowed.
• Resectable breast cancer in which pre-operative therapy is appropriate (T > 10mm
and/or node-positive).
• Archival tissue from the diagnostic pre-treatment biopsy is required. This sample
should be identified at screening and shipped by Week 4. If archival tissue is not
available, the subject is not eligible for the study.
• Agreeable to repeat breast biopsy at 3 weeks after initiation of treatment.
• Candidate for either letrozole or anastrozole, as determined by the treating physician
• Left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiogram (ECHO)
or multi-gated acquisition scan (MUGA) documented within 4 weeks prior to the study
treatment.
• Demonstrate adequate organ function as defined below; all screening labs to be
obtained within 28 days prior to registration.
• Hematological
• Platelet count ≥100,000/uL
• Absolute Neutrophil Count (ANC) ≥1500/uL
• Hemoglobin (Hgb) ≥10 g/dL
• Renal
---Calculated creatinine clearance: CrCl ≥60 mL/min using the Cockcroft-Gault
formula
• Hepatic
• Bilirubin ≤1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 × ULN
• Alanine aminotransferase (ALT) ≤ 2.5 × ULN
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months of registration are eligible for this trial.
• For patients with known serologic 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, the
HCV viral load must be undetectable to be eligible for this trial.
• Ability of the subject to understand and comply with study procedures for the entire
length of the study, as determined by the enrolling physician or protocol designee.
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
• Locally advanced or inflammatory breast cancer.
• Evidence of metastatic disease. Systemic imaging is not required.
• Patients with a prior or concurrent malignancy whose natural history or treatment has
the potential to interfere with the safety or efficacy assessment of the
investigational regimen are not eligible for this trial: exceptions include basal cell
or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for
which the subject has been disease-free for at least five years.
• Active infection requiring systemic therapy.
• Requirement for use of a moderate or stonr CYP3A4 inhibitor or inducer during the
study (see protocol).
• Treatment with any investigational drug within 14 days prior to registration or within
5 half-lives of the investigational product, whichever is longer.
• Subject has had major surgery within 14 days prior to registration or has not
recovered from major side effects of the surgery (tumor biopsy is not considered as
major surgery).
• Any impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection) or significantly
impair the ability to swallow capsules/tablets.
• Known history of myelodysplastic syndrome or acute myeloid leukemia.
• Subjects with any of the following conditions:
• History of abdominal fistula, gastrointestinal perforation, or intra- abdominal
abscess within 28 days prior to registration.
• Any history of cerebrovascular accident (CVA) or transient ischemic attack within
12 months prior to registration.
• History of acute coronary syndromes (including myocardial infarction, unstable
angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or
symptomatic pericarditis within 6 months prior to registration.
• Symptomatic congestive heart failure (New York Heart Association III-IV) or
documented current cardiomyopathy with left ventricular ejection fraction (LVEF)
<50%.
• Clinically significant cardiac ventricular arrhythmias (e.g. sustained
ventricular tachycardia/ventricular fibrillation) or high-grade AV block (e.g.
bifascicular block, Mobitz type II and third-degree AV block) unless a pacemaker
is in place.
• Long QT syndrome or family history of idiopathic sudden death or congenital long
QT syndrome.
• Any concurrent severe and/or uncontrolled medical condition that would, in the
investigator's judgment, cause unacceptable safety risks, contraindicate subject
participation in the clinical study or compromise compliance with the protocol.
Breast Cancer, HER2-positive Breast Cancer, ER Positive Breast Cancer, PR-Positive Breast Cancer, Breast
Testing the Safety and Effectiveness of Radiation-based Treatment (Lutetium Lu 177 Dotatate) for Metastatic Prostate Cancer That Has Neuroendocrine Cells
This phase II trial studies how well lutetium Lu 177 dotatate works in treating patients with
prostate cancer with neuroendocrine differentiation that has spread to other places in the
body (metastatic). Neuroendocrine differentiation refers to cells that have traits of both
hormone-producing endocrine cells and nerve cells. These cells release hormones into the
blood in response to a signal from the nervous system. Hormones are biological substances
that circulate through the bloodstream to control the activity of other organs or cells in
the body. Lutetium Lu 177-dotate is a radioactive drug. It binds to a protein called
somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu
177-dotatate builds up in these cells and gives off radiation that may kill them. It is a
type of radioconjugate and a type of somatostatin analog. Treatment with Lutetium Lu 177
dotatate may shrink the tumor in a way that can be measured in patients with metastatic
prostate cancer with neuroendocrine differentiation.
John Floberg, Assistant Professor
Male
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05691465
Show full eligibility criteria
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Inclusion Criteria:
• PRE-REGISTRATION ELIGIBILITY
• Patients must have metastatic prostate cancer with neuroendocrine differentiation, as
determined by at least one of the following:
• Histologically confirmed small cell or neuroendocrine cancer from a primary
prostate or metastatic biopsy. Neuroendocrine prostate cancer includes mixed
small cell with adenocarcinoma histology, as well as small or large cells with
positive neuroendocrine markers (e.g., chromogranin or synaptophysin)
• Prostate adenocarcinoma with molecular features of neuroendocrine differentiated
cancer (e.g., 2 of the following 3: PTEN, TP53, or RB loss)
• Progression of visceral metastases in the absence of PSA progression
• Serum chromogranin A > 5x normal limit, or neuron-specific enolase > 2x normal
• Age >= 18 years. Prostate cancer is typically a disease of older men, with the average
age at diagnosis being 65 years. Consequently, because the research topic is not
relevant to children, no children will be included in this study. There is no upper
limit to the age of participants eligible for this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 8 g/dL, prior to each dose of lutetium lu 177 dotatate
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x
institutional ULN
• Creatinine Cockcroft calculated creatinine clearance of >= 60 mL/min OR
• Glomerular filtration rate (GFR) of 60 mL/min/1.73 m^2 unless data exists supporting
safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• 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 follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression
• 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 are eligible for this trial
• Patients should be New York Heart Association Functional Classification of class 2B or
better
• Current disease progression according to PCWG3 criteria
• Ongoing use of luteinizing hormone-releasing hormone (LHRH) agonists/antagonists will
be required (unless prior bilateral orchiectomy or pure neuroendocrine carcinoma
histology) to maintain testosterone at castrate levels. Patients with a pure
neuroendocrine carcinoma histology do not need to be undergoing LHRH
agonist/antagonist therapy
• No concurrent use of other anti-cancer therapies
• Pregnancy Precaution: The effects of lutetium lu 177 dotatate on the developing human
fetus are unknown. For this reason and because radionuclides are known to be
teratogenic, male participants and their female partners must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while her male 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 4 months after completion of lutetium lu 177
dotatate administration. Patients must not donate sperm during the study and for 3
months after the last 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
• Patients will undergo a Gallium 68 Dotatate PET scan after enrollment. The Gallium 68
Dotatate PET must be positive to proceed with lutetium Lu 177 dotatate therapy. A
positive scan will be defined as at least one lesion with an maximum standardized
uptake value (SUVmax) > the average standardized uptake value (SUV) of normal liver.
The positive lesion(s) can be in any location (bone metastases or visceral
metastases). Patients with only bone metastases will be allowed
• REGISTRATION ELIGIBILITY: The gallium 68 dotatate PET is positive. A positive scan
will be defined as at least one lesion with an maximum standardized uptake value
(SUVmax) > the average SUV of normal liver. The positive lesion(s) can be in any
location (bone metastases or visceral metastases). Patients with only bone metastases
will be allowed.
• REGISTRATION ELIGIBILITY: Absolute neutrophil count ≥ 1,500/mcL
• REGISTRATION ELIGIBILITY: Platelets ≥ 100,000/mcL
• REGISTRATION ELIGIBILITY: Hemoglobin ≥ 8 g/dL, prior to each dose of lutetium Lu 177
dotatate
• REGISTRATION ELIGIBILITY: Total bilirubin ≤1.5 × institutional upper limit of normal
(ULN)
• REGISTRATION ELIGIBILITY: AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
• REGISTRATION ELIGIBILITY: Creatinine Cockcroft calculated creatinine clearance of ≥ 60
mL/min OR
• REGISTRATION ELIGIBILITY: Glomerular filtration rate (GFR) of 60 mL/min/1.73 m^2
unless data exists supporting safe use at lower kidney function values, no lower than
30 mL/min/1.73 m^2
Exclusion Criteria:
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Lutetium Lu 177 dotatate
• As per the Food and Drug Administration (FDA) package insert for Lutetium Lu 177
dotatate, use of long-acting somatostatin analogs (e.g., long-acting octreotide) is
prohibited within 4 weeks prior to initiating Lutetium Lu 177 dotatate and during
treatment. Use of short-acting somatostatin analogs is prohibited within 24 hours
prior to initiating Lutetium Lu 177 dotatate and during treatment. Long-acting
somatostatin analogs or short-acting somatostatin analogs will be allowed if the
patient has a history of carcinoid syndrome and requires long-acting or short-acting
somatostatin analogs for the control of his functional syndrome
• Patients with uncontrolled intercurrent illness
• Any of the following within 6 months before starting treatment: stroke, myocardial
infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft;
congestive heart failure New York Heart Association (NYHA) Class III or IV
• Uncontrolled hypertension as indicated by a systolic blood pressure >= 160 mmHg or
diastolic blood pressure >= 100 mmHg at screening
Metastatic Prostate Adenocarcinoma With Neuroendocrine Differentiation, Metastatic Prostate Neuroendocrine Carcinoma, Metastatic Prostate Small Cell Neuroendocrine Carcinoma, Stage IV Prostate Cancer AJCC v8, Prostate
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
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, 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
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
Hide eligibility criteria
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
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, Locally Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Malignant Solid Neoplasm
Study Transplanting Bone Marrow Cells Into Salivary Glands to Treat Dry Mouth Caused by Radiation Therapy
The goal of this clinical research study is to evaluate the safety and tolerability of
injecting certain cells that you produce in your bone marrow called mesenchymal stem cells
(MSCs) into your salivary glands.
Participants will have head and neck cancer that was treated with radiation therapy, and in
this study will:
- Undergo a collection of bone marrow using a needle;
- Donate saliva;
- Undergo a salivary gland ultrasound; and,
- Complete questionnaires that ask about dry mouth
Participants can expect to be in this study for up to 30 months.
Randall Kimple, MD, PhD
All
18 Years to 90 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT05820711
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Inclusion Criteria:
• History of histological diagnosis of head and neck cancer (HNC) that was treated with
radiation therapy and currently clinically or radiologically no evidence of disease
(NED)
• Xerostomia, defined as patient reported salivary function (pre-treatment) ≤ 80% of
healthy (pre-radiation)
• ≥ 18 years of age, ≤ 90 years of age.
• Patients ≥ 2 years from completion of radiation therapy for HNC
• Karnofsky performance status ≥ 70, patient eligible for bone marrow aspirate with
wakeful anesthesia
• Willing and able to give informed consent
• Radiographically confirmed submandibular gland(s)
Exclusion Criteria:
• Salivary gland disease (i.e., sialolithiasis)
Head and Neck Cancer, Xerostomia, Lip, Oral Cavity and Pharynx, Larynx, Head and Neck
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
Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder
This study is open to adults with advanced cancer in the biliary tract, pancreas, lung, or
bladder. This is a study for people for whom previous treatment was not successful or no
treatment exists.
The purpose of this study is to find out whether a medicine called BI 907828 helps people
with cancer in the biliary tract, pancreas, lung, or bladder. BI 907828 is a so-called MDM2
inhibitor that is being developed to treat cancer. All participants take BI 907828 as a
tablet once every 3 weeks. Participants may continue to take BI 907828 as long as they
benefit from treatment and can tolerate it. They visit the study site regularly. At the study
site, doctors regularly check the size of the tumour and whether it has spread to other parts
of the body. The doctors also regularly check participants' health and take note of any
unwanted effects.
Jeremy Kratz, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05512377
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Inclusion Criteria:
• Diagnosis of a solid tumour which meets the criteria for an open trial cohort:
• Cohorts 1 and 1-CN (biliary tract adenocarcinoma): Locally advanced or metastatic
biliary tract adenocarcinoma (intra- and extrahepatic cholangiocarcinoma,
gallbladder cancer, and ampullary cancer).Patients must have unresectable disease
and have received all available conventional therapies known to confer clinical
benefit for their disease based on local approved standards; or (in the opinion
of the investigator) patients are unlikely to tolerate or derive clinically
meaningful benefit from appropriate standard of care therapy.
• Cohort 2 (pancreatic ductal adenocarcinoma): Locally advanced or metastatic
pancreatic ductal adenocarcinoma. Patients must have unresectable disease and
have received all available conventional therapies known to confer clinical
benefit for their disease based on local approved standards.
• Cohort 3 (lung adenocarcinoma): Locally advanced or metastatic lung
adenocarcinoma. Patients must have unresectable disease and have received all
available conventional therapies known to confer clinical benefit for their
disease based on local approved standards.
• Cohort 4 (urothelial bladder cancer): Locally advanced or metastatic urothelial
bladder cancer. Patients must have unresectable disease and have received all
available conventional therapies known to confer clinical benefit for their
disease based on local approved standards.
• Written pathology report / molecular profiling report indicating Mouse double minute 2
homolog (MDM2) amplification or a copy number ≥8 and tumor protein 53 (TP53) wild-type
status. This must have been confirmed with a tissue-based test. A test with liquid
biopsy is not accepted.
• Archival tissue (formalin fixed paraffin embedded [FFPE] tumour blocks or slides) must
be provided for retrospective confirmation of MDM2 amplification and TP53 status.
• Presence of at least 1 measurable target lesion according to Response Evaluation
Criteria in Solid Tumours (RECIST) version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Patient must be willing to donate mandatory blood samples for the pharmacokinetics,
pharmacodynamics, and biomarker analyses
• Adequate organ function
• All toxicities related to previous anti-cancer therapies have resolved to ≤Common
Terminology Criteria for Adverse Events (CTCAE) Grade 1 prior to trial treatment
administration (except for alopecia and amenorrhea / menstrual disorders which can be
of any grade and peripheral neuropathy which must be ≤CTCAE Grade 2).
• Life expectancy ≥3 months at the start of treatment in the opinion of the
investigator.
• 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.
• Male or female patients ≥18 years old at the time of signature of the ICF. Women of
childbearing potential (WOCBP) and men able to father a child must be ready and able
to use 2 medically acceptable methods of birth control per ICH M3 (R2) that result in
a low failure rate of less than 1% per year when used consistently and correctly
beginning at screening, during trial participation, and until 6 months and 12 days
after last dose for women and 102 days after last dose for men. A list of
contraception methods meeting these criteria is provided in the patient information.
Exclusion Criteria:
• Previous administration of brigimadlin (BI 907828) or any other MDM2-p53 or mouse
double minute 4 (MDMX, MDM4)-p53 antagonist.
• Active bleeding, significant risk of haemorrhage (e.g. previous severe
gastrointestinal bleeding, previous haemorrhagic stroke at any time), or current
bleeding disorder (e.g. haemophilia, von Willebrand disease).
• Major surgery (major according to the investigator's assessment) performed within 4
weeks prior to start of trial treatment or planned within 6 months after screening
(e.g. hip replacement).
• Clinically significant previous or concomitant malignancies in the opinion of the
investigator affecting the efficacy and/or outcome of the trial.
• Patients who must or intend to continue the intake of restricted medications or any
drug considered likely to interfere with the safe conduct of the trial.
• Currently enrolled in another investigational device or drug trial.
• Any history of, or concomitant condition that, in the opinion of the investigator,
would compromise the patient's ability to comply with the trial or interfere with the
evaluation of the safety and efficacy of the trial drug.
• Patients not expected to comply with the protocol requirements or not expected to
complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other
condition that, in the investigator's opinion, makes the patient an unreliable trial
participant).
Further exclusion criteria apply.
Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic Fibrosis (CF) Participants 1 Through 11 Years of Age
The purpose of this study is to evaluate the pharmacokinetics, safety, tolerability and
efficacy of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants with at
least 1 triple combination responsive (TCR) mutation in the cystic fibrosis transmembrane
conductance regulator (CFTR) gene.
Hara Levy, MD
All
1 Year to 11 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05422222
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Key
Inclusion Criteria:
• Participants with stable CF and at least 1 TCR mutation (including F508del) in the
CFTR gene
Key
Exclusion Criteria:
• History of solid organ, hematological transplantation, or cancer
• Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh
Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
• Lung infection with organisms associated with a more rapid decline in pulmonary status
Other protocol defined Inclusion/Exclusion criteria may apply.
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
Study of Epetraborole in Patients With Treatment-refractory MAC Lung Disease
This is a pivotal Phase 2/3, double-blind, placebo-controlled study of epetraborole + OBR
(Optimized Background Regimen) versus placebo + OBR in patients with treatment-refractory MAC
lung disease. This study will enroll adult patients with treatment-refractory MAC lung
disease who meet all eligibility criteria (including clinical, radiographic, and
microbiological criteria).
Elizabeth Misch, MD
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT05327803
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Inclusion Criteria:
1. Male or female patients who are 18 years of age or older.
2. Willing and able to provide written informed consent.
3. Patients with a diagnosis of treatment-refractory MAC lung disease consisting of all
of the following (a) Microbiological, (b) Clinical, and (c) Radiographic criteria:
1. Microbiological criteria:
• One Pre-Study MAC-positive respiratory specimen. Documentation of a MAC
positive specimen collected per standard of care within 6 months prior to
signing the informed consent form (ICF).
• One Screening MAC-positive expectorated or induced sputum sample.
2. Clinical criteria: At least 2 of the following patient-reported clinical
symptoms:
• Cough with sputum production
• Cough without sputum
• Chest congestion
• Hemoptysis
• Dyspnea
• Fatigue
• Night sweats or unusual sweating
3. Radiographic criteria: Non contrast Chest CT scan within 6 months prior to
signing the ICF with abnormalities consistent with MAC lung disease.
4. OBR criteria: An OBR is a combination regimen that consists of ≥2
antimycobacterial agents. The patient-specific OBR must be administered for a
minimum duration of 6 consecutive months that is either ongoing at the time of
Screening or was stopped or paused no more than 12 months before screening. The
OBR regimen administered during Screening must be continued after randomization.
4. Patients who are willing to comply with all the study activities and procedures
throughout the duration of the study and comply with all planned study visits and
study procedures from Screening through the LFU Visit.
5. All patients must agree to use an effective method of birth control.
6. Patients expected to survive with continued antimycobacterial therapy and appropriate
supportive care from Screening through the LFU Visit, in the judgment of the
Investigator.
Exclusion Criteria:
1. Patients with a presence of any suspected or confirmed disease or condition at
Screening or the time of randomization that, in the opinion of the Investigator, may
confound the assessment of symptom-based clinical response.
2. Patients with active pulmonary malignancy or any malignancy that required or would
require chemotherapy or radiation therapy within 1 year prior to randomization through
the LFU Visit.
3. Patients with creatinine clearance (CrCl) of ≤30 mL/min, as estimated by the Cockcroft
Gault formula, at Screening.
4. Patients with hemoglobin <10.0 g/dL or <6.2 mmol/L at Screening; donation of blood or
plasma within 28 days prior to randomization; or symptomatic loss of blood or
hemorrhage within 28 days prior to randomization.
5. Patients with severe hemoptysis within 28 days prior to randomization, defined as >100
mL over any 24-hour period or severe or extremely severe hemoptysis.
6. Patients with severe hepatic impairment, as evidenced by alanine aminotransferase
(ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN) or total
bilirubin >2 × ULN, or clinical signs of cirrhosis or end-stage hepatic disease.
7. Patients who are pregnant or breastfeeding.
8. Patients with a mean QT interval corrected using Fridericia's formula (QTcF) >480 msec
based on triplicate 12-lead ECGs at Screening.
9. Patients with an immunodeficiency or an immunocompromised condition and risk for an
opportunistic pulmonary infection.
10. Patients with an anticipated start of new non-study antimycobacterial therapy to be
administered at any time between Screening and Month 6.
11. Patients who have received any investigational medication during the 30 days or 5
half-lives, whichever is longer, prior to randomization.
12. Patients with any prior exposure to epetraborole.
13. Patients with any condition that, in the opinion of the Investigator, interferes with
the ability to safely complete the study or adhere to study requirements, including
the patient's inability or unwillingness to comply with all study assessments and
visits.
MAC Lung Disease, Treatment Refractory MAC Lung Disease, Other
Liposomal Irinotecan With TAS102 and Bevacizumab for Patients With Metastatic Colorectal Cancer
This study is being done to see if combining liposomal irinotecan with TAS102 and bevacizumab
confers clinical benefit for patients with treatment refractory metastatic colorectal cancer.
Dustin Deming, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05854498
Show full eligibility criteria
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Inclusion Criteria:
• Patients must be ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance must be 0 or 1.
• Patients must have a histologically or cytologically confirmed diagnosis of colorectal
adenocarcinoma and be metastatic or unresectable.
• The cancer must be mismatch repair proficient.
• Patients must have had prior treatment with 5-fluorouracil, oxaliplatin, irinotecan
containing regimens. If RAS wild-type must have received prior anti-EGFR therapy with
either cetuximab or panitumumab. If RAS wild-type and HER2 positive then must have had
a prior HER2 targeted therapy.
Exclusion Criteria:
• Uncontrolled concurrent medical illness that would not allow for the completion of the
planned therapy.
• Patients whose cancers possess BRAF V600 mutations are excluded.
• Patients must stop the use of strong inducers/inhibitors of CYP3A4 at least 2 weeks
before initiating therapy.
• Patients must not have mismatch repair deficient or microsatellite instability high
cancers.
• Patients must not have received prior TAS102.
Metastatic Colorectal Cancer, Colon, Colon and Rectum
(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination
with sunitinib. This is a multi-part study that will enroll approximately 426 patients. Part
1 consists of two evaluations: 1) confirming the dose of an updated formulation of CGT9486 to
be used in subsequent parts in approximately 20 patients who have received at least one prior
line of therapy for GIST and 2) evaluating for drug-drug interactions between CGT9486 and
sunitinib in approximately 18 patients who have received at least two prior tyrosine kinase
inhibitors (TKIs) for GISTs. The second part of the study will enroll approximately 388
patients who are intolerant to, or who failed prior treatment with imatinib only and will
compare the efficacy of CGT9486 plus sunitinib to sunitinib alone with patients being
randomized in a 1:1 manner.
Howard Bailey, M.D.
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05208047
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Key
Inclusion Criteria:
1. Histologically confirmed locally advanced, metastatic, and/or unresectable GIST.
Molecular pathology report must be available for Part 2; if molecular pathology report
is unavailable or inadequate, an archival or fresh tumor tissue sample will be
required to evaluate mutational status prior to randomization.
2. Documented disease progression on or intolerance to imatinib
3. Subjects must have received the following treatment:
• Part 1a: Treatment with ≥1 prior lines of therapy for GIST
• Part 1b: Treatment with ≥2 prior TKI for GISTs
• Part 2: Prior treatment with imatinib only
4. Have at least 1 measurable lesion according to mRECIST v1.1
5. ECOG •0 to 2
6. Have clinically acceptable local laboratory screening results (clinical chemistry and
hematology) within certain limits
Key
Exclusion Criteria:
1. Known PDGFR driving mutations or known succinate dehydrogenase deficiency
2. Clinically significant cardiac disease
3. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study
drug
4. Gastrointestinal abnormalities including, but not limited to, significant nausea and
vomiting, malabsorption, external biliary shunt, or significant bowel resection that
would preclude adequate absorption
5. Any active bleeding excluding hemorrhoidal or gum bleeding
6. Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis
C virus (HCV) antibody.
7. Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening
8. Received strong CYP3A4 inhibitors or inducers
9. Received sunitinib within 3 weeks (Part 1a, Part 1b)
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