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within category "Digestive Health & Liver Disease"
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Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)
The purpose of this study is to find out whether the study drug, LY3537982, is safe and
effective in cancer patients who have a specific genetic mutation (KRAS G12C). Patients must
have already received or were not able to tolerate the standard of care, except for specific
groups who have not had cancer treatment. The study will last up to approximately 4 years.
Dustin Deming, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04956640
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Inclusion Criteria:
• Patients have measurable disease per Response Evaluation Criteria in Solid Tumors
version 1.1 (RECIST v1.1).
• Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or
circulating tumor deoxyribonucleic acid (DNA).
• Participants must have a histological or a cytologically proven diagnosis of locally
advanced, unresectable, and/or metastatic cancer and meet cohort-specific criteria.
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Have adequate organ function.
• Have discontinued all previous treatments for cancer with resolution of any
significant ongoing adverse events (AEs), (except in certain scenarios).
• Must be able to swallow capsule/tablet.
• Agree and adhere to contraceptive use, if applicable.
• For some parts of the study, (i.e., one of the two arms with LY3537982 in combination
with pembrolizumab and the arm of LY3537982 in combination with pembrolizumab,
pemetrexed, and platinum therapy) histologically or cytologically confirmed Stage
IIIB-IIIC or Stage IV NSCLC that is previously untreated in the advanced/metastatic
setting and not suitable for curative intent radical surgery or radiation therapy.
Previously untreated patients who received adjuvant and neoadjuvant therapy are
eligible if the last dose of the systemic treatment was completed at least 6 months
prior to enrollment. For untreated patients in the arm with LY3537982 in combination
with pembrolizumab noted above, a single cycle of pembrolizumab may be initiated
within 21 days prior to enrollment. For untreated patients in the arm of LY3537982 in
combination with pembrolizumab, pemetrexed, and platinum therapy, a single cycle of
any or all of the drugs other than LY3537982 may be initiated within 21 days prior to
enrollment. Start of study treatment may be delayed to allow sufficient time for
recovery from treatment-related toxicity.
• For one part of the study, participants must have received at least one prior
oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC.
Exclusion Criteria:
• Disease suitable for local therapy administered with curative intent.
• Have an active, ongoing, or untreated infection.
• Have a serious pre-existing medical condition(s) that, in the judgment of the
investigator, would preclude participation in this study.
• Have a serious cardiac condition.
• Have a second active primary malignancy or have been diagnosed and/or treated for an
additional malignancy within 3 years prior to enrollment.
• Have symptomatic central nervous system (CNS) malignancy or metastasis and/or
carcinomatous meningitis. Patients with treated CNS metastases are eligible for this
study if their disease is asymptomatic, radiographically stable for at least 30 days,
and they do not require treatment with steroids in the two-week period prior to study
treatment. This only applies to some parts of the study.
• Have received prior treatment with any KRAS G12C small molecule inhibitor, except in
certain scenarios where such prior therapy is allowed as per protocol.
• The following patients will be excluded from some parts of the study:
• Experienced certain serious side effects with prior immunotherapy.
• Have an active autoimmune disease that has required systemic anti-autoimmune
treatment in the past 2 years.
• Have received a live vaccine within 30 days prior to the first dose of study
drug.
• Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the trial through 180 days after the last dose of study
medication.
• Known allergic reaction against any of the components of the study treatments.
Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Endometrial Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Biliary Tract Neoplasms, Lip, Oral Cavity and Pharynx, Esophagus, Colon, Anus, Liver, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Melanoma, Skin, Kaposi's Sarcoma, Breast, Cervix, Corpus Uteri, Other Female Genital, Other Male Genital, Kidney, Eye and Orbit, Brain and Nervous System, Other Endocrine System, Ill-Defined Sites, Anal, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Ovary, Sarcoma, Uterus
Comparing High-Dose Cisplatin Every Three Weeks to Low-Dose Cisplatin Weekly When Combined With Radiation for Patients With Advanced Head and Neck Cancer
This phase II/III trial compares the effect of the combination of high-dose cisplatin every
three weeks and radiation therapy versus low-dose cisplatin weekly and radiation therapy for
the treatment of patients with locoregionally advanced head and neck cancer. Chemotherapy
drugs, such as 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.
Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. This study
is being done to find out if low-dose cisplatin given weekly together with radiation therapy
is the same or better than high-dose cisplatin given every 3 weeks together with radiation
therapy in treating patients with head and neck cancer.
Paul Harari, MD
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT05050162
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Inclusion Criteria:
• Pathologically (histologically or cytologically) proven diagnosis of SCCHN of the
oropharynx, larynx, hypopharynx, or p16-positive unknown primary prior to
registration; specimen from cervical lymph nodes with a well-defined primary site
documented clinically or radiologically is acceptable; in patients with carcinoma of
unknown primary this will be sufficient for pathologic confirmation without a
clinically or radiographically defined primary site
• For patients with oropharyngeal cancer (OPC)/cancer of unknown primary (CUP):
P16 status based on local site immunohistochemical tissue staining is required. A cell
block obtained from a fine needle aspiration (FNA) biopsy specimen may be used as the sole
diagnostic tissue. Centers are encouraged to contact the pathology chair for clarification
• Note: Institutions must screen patients for p16 status by immunohistochemistry (IHC)
in order to be eligible for the trial using a Clinical Laboratory Improvement
Amendments (CLIA)-certified laboratory. A rigorous laboratory accreditation process
similar to the United States (U.S.) CLIA certification, such as the provincial
accreditation status offered by the Ontario Laboratory Accreditation (OLA) Program in
Canada, the College of American Pathologists (CAP), or an equivalent accreditation in
other countries, is acceptable.
• The p16 results must be reported on the pathology report being submitted. The p16
positivity is defined as > 70% of tumor cells showing strong nuclear and/or
cytoplasmic immunostaining with p16 antibody.
• For patients with laryngeal and hypopharyngeal primaries: Analysis of p16 status
is NOT required
• Patients must have clinically or radiographically evident measurable disease
at the primary site or at nodal stations. Simple tonsillectomy or local
excision of the primary without removal of nodal disease is permitted, as is
excision removing gross nodal disease but with intact primary site. Limited
neck dissections retrieving =< 4 nodes are permitted and considered as
non-therapeutic nodal excisions
• Clinical stage (American Joint Committee on Cancer [AJCC], 8th ed.),
including no distant metastases based on the following diagnostic workup:
• History/physical examination within 60 days prior to registration
• One of the following imaging studies is required within 60 days prior to
registration:
• Computed tomography (CT) scan of neck (diagnostic quality with contrast, unless
contraindicated) OR
• Magnetic resonance imaging (MRI) of the neck (diagnostic quality with contrast, unless
contraindicated) OR
• Fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/CT of the neck; the CT
component must be of diagnostic quality with contrast, unless contraindicated.
• Note: A diagnostic quality CT or MRI with contrast or FDG-PET/CT scan of neck
performed for the purposes of radiation planning may serve as both staging and
planning tools
• One of the following imaging studies is required within 60 days prior to
registration:
• FDG-PET/CT of the chest; FDG-PET/CT scan is strongly preferred and highly recommended
to be used for eligibility OR
• Chest CT
• Exam with laryngopharyngoscopy (mirror or in office direct procedure acceptable)
within 70 days prior to registration;
• Eligibility by patient cohort;
• Non-OPC/p16-negative OPC Cohort; Tumor Site: Larynx/Hypopharynx; Clinical Staging
(AJCC, 8th ed.): T3-4 N0 or T1-4 N1-3 T2 N0 (hypopharynx only)
• Tumor Site: p16-negative OPC; Clinical Staging (AJCC, 8th ed.): T2N1, T1-4 N2-3,
or T3-4 N0-1
• p16-positive OPC/CUP Cohort;
• Tumor Site: OPC; Smoking Status: =< 10 pack-years; Clinical Staging (AJCC, 8th
ed.): T1-3 N2-3 or T4 N0-3
• Tumor Site: OPC; Smoking Status: > 10 pack-years; Clinical Staging (AJCC, 8th
ed.): T1N2-3, T2N1-3 or T3-4 N0-3
• Tumor Site: CUP; Smoking Status: Any; Clinical Staging (AJCC, 8th ed.): T0 N2-3
Note: Cigar and pipe tobacco consumption is not included in calculating the lifetime
pack-years. Marijuana consumption is likewise not considered in this calculation. There is
also no clear scientific evidence regarding the role of chewing tobacco-containing products
in oropharyngeal cancer, although this is possibly more concerning given the proximity of
the oral cavity and oropharynx. In any case, investigators should not count use of
non-cigarette tobacco products in the pack-years calculation.
• Age >= 18
• Zubrod (Eastern Cooperative Oncology Group [ECOG]) performance status of 0-1 within 14
days prior to registration
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 30 days prior to
registration)
• Platelets >= 75,000 cells/mm^3 (within 30 days prior to registration)
• Hemoglobin >= 8.0 g/dL (within 30 days prior to registration)
• Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >=
8.0 g/dL is acceptable)
• Calculated creatinine clearance (CrCl) >= 50 mL/min by the Cockcroft-Gault formula
(within 30 days prior to registration)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 30 days
prior to registration) (not applicable to patients with known Gilbert's syndrome)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x
institutional ULN (within 30 days prior to registration)
• Known human immunodeficiency virus (HIV) infected patients on effective
anti-retroviral therapy with undetectable viral load within 6 months and CD4 T Cell
count > 200 cells/mm^3 are eligible for this trial. Testing is not required for entry
into protocol
• 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
• 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. Menopause is defined clinically
as 12 months of amenorrhea in a woman over 45 in the absence of other biological or
physiological causes
• Willing to use highly effective contraceptives for participants of childbearing
potential (participants who may become pregnant or who may impregnate a partner)
during therapy and for 14 months (females); for 11 months (males) following last dose
of cisplatin; this inclusion is necessary because the treatment in this study may be
significantly teratogenic
• 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:
• Patients with oral cavity cancer, nasopharynx cancer, or p16-negative cancer of
unknown primary (CUP)
• Recurrence of the study cancer
• Definitive clinical or radiologic evidence of distant metastatic disease
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable, however, any prior exposure to cisplatin is excluded
• Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields
• Severe, active co-morbidity defined as follows:
• Unstable angina requiring hospitalization in the last 6 months
• Myocardial infarction within the last 6 months
• New York Heart Association Functional Classification III/IV (Note: 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.)
• Persistent grade 3-4 (CTCAE version 5.0) electrolyte abnormalities that cannot be
reversed despite replacement as indicated by repeat testing
• Patient must not have an active infection requiring IV antibiotics prior to
registration;
• Other chronic renal disease like nephrotic syndrome, that could be worsened by
cisplatin therapy
• History of allogenic organ transplantation
• Any symptomatic peripheral sensory neuropathy grade >= 2 (CTCAE version 5.0);
• Pregnancy and individuals unwilling to discontinue nursing
• History of hypersensitivity to cisplatin or platinum-containing compounds
Lip, Oral Cavity and Pharynx, Larynx, Unknown Sites, Head and Neck, Advanced Head and Neck Squamous Cell Carcinoma, Advanced Hypopharyngeal Squamous Cell Carcinoma, Advanced Laryngeal Squamous Cell Carcinoma, Advanced Oropharyngeal Squamous Cell Carcinoma, Squamous Cell Carcinoma of Unknown Primary
MSC in Patients With Xerostomia Post XRT in Head and Neck Cancer
This is a single center pilot study designed to determine the safety and tolerability of
autologous bone marrow-derived Mesenchymal Stromal Cells (MSCs) in patients with xerostomia
(dry mouth) after undergoing radiation therapy (XRT) for head and neck cancer (HNC). Up to 12
participants will be enrolled and can expect to be on study for up to 2 years.
Randall Kimple, MD, PhD
All
18 Years to 90 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT04489732
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Inclusion Criteria:
• Willing to provide informed consent
• Willing to comply with all study procedures and be available for the duration of the
study
• Histological diagnosis of Head and Neck Cancer (HNC) and ≥ 2 years from completion of
treatment for HNC, either clinically or radiologically No Evidence of Disease (NED),
as assessed by ENT or Radiation Oncologist within 28 days of study registration
• Individuals at least 18 years of age and no older than 90 years of age
• Xerostomia defined as less than or equal to 80 percent of baseline (pre-radiation)
salivary function per patient estimate
• Karnofsky performance status ≥ 70, patient eligible for bone marrow aspirate with
wakeful anesthesia
• Radiographically confirmed bilateral submandibular glands
• Females of childbearing potential must agree to have a negative urine or serum
pregnancy test within 7 days prior to bone marrow biopsy. A female of child-bearing
potential is any woman (regardless of sexual orientation, having undergone a tubal
ligation, or remaining celibate by choice) who meets the following criteria:
• has not undergone a hysterectomy or bilateral oophorectomy; or
• has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months)
• Women of childbearing potential in sexual relationships with men must have used an
acceptable method of contraception for 30 days prior to study registration and agree
to use an acceptable method of contraception until 4 weeks after completing study
treatment. Males must agree to avoid impregnation of women during and for four weeks
after completing study treatment through use of an acceptable method of contraception.
Note: Acceptable method of contraception includes, but is not limited to, barrier with
additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started
at least 30 days prior to study enrollment), intercourse with men who underwent vasectomy)
Exclusion Criteria:
• History of sialolithiasis
• Patients with one submandibular gland
• History of autoimmune diseases affecting salivary glands, including Sjögren's
syndrome, lupus, scleroderma, type I diabetes, sarcoidosis, and amyloidosis
• Chronic graft vs host disease
• Untreated oral candidiasis
• Use of anti-cholinergic medications (e.g. atropine, ipratropium, oxybutynin,
scopolamine, solifenacin, tiotropium, etc…) while enrolled on study
• Malignancy within the past 2 years, except adequately treated stage I lung cancer, low
risk prostate cancer that has been treated or is undergoing active surveillance,
adequately treated non-melanoma skin cancer, adequately treated ductal carcinoma in
situ (DCIS), or adequately treated stage I cervical cancer
• Expected life expectancy ≤ 6 months
• Lidocaine allergy
• Use of investigational drugs, biologics, or devices within 30 days prior to enrollment
• Women who are pregnant, lactating or planning on becoming pregnant during the study
• Not suitable for study participation due to other reasons at the discretion of the
investigators
Xerostomia Following Radiotherapy, Lip, Oral Cavity and Pharynx, Head and Neck
A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
This phase III trial compares the safety and effect of adding vinorelbine to vincristine,
dactinomycin, and cyclophosphamide (VAC) for the treatment of patients with high risk
rhabdomyosarcoma (RMS). High risk refers to cancer that is likely to recur (come back) after
treatment or spread to other parts of the body. This study will also examine if adding
maintenance therapy after VAC therapy, with or without vinorelbine, will help get rid of the
cancer and/or lower the chance that the cancer comes back. Vinorelbine and vincristine are in
a class of medications called vinca alkaloids. They work by stopping cancer cells from
growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only
used in cancer chemotherapy. It works by damaging the cell's deoxyribonucleic acid (DNA) and
may kill cancer cells. Cyclophosphamide is in a class of medications called alkylating
agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the
body's immune response. Vinorelbine, vincristine, dactinomycin and cyclophosphamide are
chemotherapy medications that work in different ways to stop the growth of cancer cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. This trial may have the potential to eliminate rhabdomyosarcoma for a long time or
for the rest of patient's life.
Kenneth Desantes, M.D.
All
up to 50 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04994132
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Inclusion Criteria:
• Patients must be =< 50 years of age at the time of enrollment
• Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based
upon institutional histopathologic classification are eligible to enroll on the study
based upon stage, group, and age, as below. FOXO1 fusion status must be determined by
week 4 (day 28) of therapy. RMS types included under embryonal RMS (ERMS) include
those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as
ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the
2020 World Health Organization (WHO) Classification as ERMS (classic, dense and
botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical
spindle cell ERMS variant and the newly recognized sclerosing RMS variant).
Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in
the ICR and includes classic and solid variants
• ERMS
• Stage 4, group IV, >= 10 years of age
• ARMS
• Stage 4, group IV Patients will be eligible to remain on protocol therapy
based upon stage, group, and age
• Bone marrow metastatic disease is based on morphologic evidence of RMS based on
hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow
involvement on H&E, patients with bone marrow involvement detected ONLY by flow
cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in
situ hybridization (FISH), or immunohistochemistry will NOT be considered to have
clinical bone marrow involvement for the purposes of this study
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (must be
performed within 7 days prior to enrollment):
• Age; Maximum serum creatinine (mg/dL)
• 1 month to < 6 months; 0.4 mg/dL (male); 0.4 mg/dL (female)
• 6 months to < 1 year; 0.5 mg/dL (male); 0.5 mg/dL (female)
• 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
• 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
• 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
• 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
• 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
• >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within
7 days prior to enrollment)
• If there is evidence of biliary obstruction by tumor, then total bilirubin must
be < 3 x ULN for age
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with evidence of uncontrolled infection are not eligible
• RMS that is considered a second malignancy and previous cancer(s) that were treated
with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is
allowed
• Patients with central nervous system involvement of RMS as defined below:
• Malignant cells detected in cerebrospinal fluid
• Intra-parenchymal brain metastasis separate and distinct from primary tumor
(i.e., direct extension from parameningeal primary tumors is allowed).
• Diffuse leptomeningeal disease
• Patients who have received any chemotherapy (excluding steroids) and/or radiation
therapy for RMS prior to enrollment.
• Note: the following exception:
• Patients requiring emergency radiation therapy for RMS. These patients are
eligible, provided they are consented to ARST2031 prior to administration of
radiation
• Note: Patients who have received or are receiving chemotherapy or radiation for
non-malignant conditions (e.g. autoimmune diseases) are eligible. Patients must
discontinue chemotherapy for non-malignant conditions prior to starting protocol
therapy
• Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients
must not have received drugs that are moderate to strong CYP3A4 inhibitors and
inducers within 7 days prior to study enrollment
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
Alveolar Rhabdomyosarcoma, Botryoid-Type Embryonal Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Metastatic Embryonal Rhabdomyosarcoma, Metastatic Rhabdomyosarcoma, Solid Alveolar Rhabdomyosarcoma, Spindle Cell Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Soft Tissue, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma
The purpose of this research is to see if a new magnetic resonance imaging (MRI) method will
be able to improve the images taken of the abdomen. This new method includes some changes to
help avoid movements that may disrupt the images like breathing, heartbeats and other
involuntary motion that occurs in the abdomen. This study will these methods in healthy
volunteers and validate them in patients with known liver metastases in a single
contrast-enhanced MRI visit.
Diego Hernando
All
18 Years and over
N/A
This study is also accepting healthy volunteers
NCT05261633
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Inclusion Criteria for Healthy Volunteers:
• 18 years of age or older
Exclusion Criteria for Healthy Volunteers:
• Patients with contraindication to MRI (e.g. pacemaker, contraindicated metallic
implants, claustrophobia, etc)
• Pregnant or trying to become pregnant (as determined by self-report during MRI safety
screening)
Inclusion Criteria for Patients:
• 18 years of age or older
• Radiologically visible solid tumor liver metastasis:
• At least one metastatic liver lesion must be a minimum of 1 cm in longest
diameter
• And must not have been treated with locoregional therapies, such as ablation or
radiation.
Exclusion Criteria for Patients:
• Patients with contraindication to MRI (e.g. pacemaker, contraindicated metallic
implants, claustrophobia, etc)
• Patients with known contraindication to GBCA such as severe kidney disease or
previously documented GFR < 30 ml/min/1.73 m2
• Patients requiring intravenous (IV) conscious sedation for imaging are not eligible;
patients requiring mild, oral anxiolytics for the MRI will be allowed to participate
as long as the following criteria are met:
• The subject has their own prescription for the medication.
• The informed consent process is conducted prior to the self-administration of
this medication
• They come to the research visit with a driver
• Pregnant or trying to become pregnant (as determined by self-report during MRI safety
screening)
• Stent in bile ducts
• Partial hepatectomy
COVID Protection After Transplant-Immunosuppression Reduction (CPAT-ISR)
This study will enroll individuals who have:
- Completed primary series of mRNA COVID-19 vaccine, and
- An antibody response ≤ 2500 U/mL measured at least 30 days after the last dose of
vaccine.
This group of patients is at high risk for severe COVID-19 disease due to pharmacologic
immunosuppression and a high prevalence of non-transplant risk factors such as obesity and
diabetes.
Jacqueline Garonzik Wang
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05077254
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Inclusion Criteria:
Individuals who meet all the following criteria are eligible for enrollment as study
participants-
1. Able to understand and provide informed consent
2. Individual ≥18 years of age.
3. Recipient of a kidney or liver transplant ≥12 months prior to enrollment, without
allograft rejection in the 6 months preceding enrollment
4. Negative for anti-donor human leukocyte antigens (HLA) antibodies at screening
(Central Lab Test Determination).
5. Currently taking one of the following tacrolimus-based immunosuppressive regimens:
• Tacrolimus plus Mycophenolate Mofetil (MMF) or Mycophenolic Acid (MPA), with or
without a corticosteroid
• Tacrolimus with trough ≥ 5ng/mL with or without ≤5 mg of prednisone or equivalent
6. Received a minimum of 3 doses of either the Moderna coronavirus infectious disease 19
(COVID-19) vaccine or Pfizer-BioNTech COVID-19 vaccine
7. Participant must be ≥ 60 days after completion of primary vaccination or receipt of
the most recent booster dose with any authorized or approved monovalent or bivalent
COVID-19 vaccine at the time of study vaccine.
8. Serum antibody negative or low (titer ≤ 2500 U/mL) at ≥ 30 days from the last dose of
mRNA COVID-19 vaccine and ≥ 30 days following receipt of a monoclonal antibody product
or convalescent plasma for COVID-19, measured using the Roche Elecsys® anti-SARS-CoV-2
S assay.
9. Participant's transplant physician or midlevel practitioner who is clinically licensed
to prescribe and manage immunosuppression must confirm the participant's eligibility
based on medical history.
Exclusion Criteria:
Individuals who meet any of these criteria are not eligible for enrollment as study
participants-
1. Currently on an immunosuppressive regimen different from the three regimens described
in the Inclusion Criteria, for example (but not limited to) those including sirolimus,
everolimus, belatacept, or azathioprine
2. Recipient of any allograft other than a kidney or liver
3. Participant is pregnant
4. Any past history of Donor Specific Antibody (DSA) using local site standards
5. Prior receipt of the Moderna COVID-19 Vaccine 2023-2024 or Pfizer-BioNTech COVID-19
Vaccine 2023-2024.
6. Currently taking any systemic immunosuppressive agent, other than their prescribed
transplant immunosuppression
7. Known history of severe allergic reaction to any component of an authorized or
licensed COVID-19 vaccine
8. Thrombotic events, myocarditis, or pericarditis temporally associated with a prior
dose of COVID-19 vaccine
9. History of heparin-induced thrombocytopenia
10. Any change in transplant immunosuppression regimen (drug or dose) in response to
suspected or proven rejection within the last 6 months
11. More than minimal graft dysfunction, in accordance with study definition
12. Receipt of any cellular depleting agent (e.g. antithymocyte globulins (ATG),
rituximab, alemtuzumab, Cyclophosphamide) within 12 months preceding enrollment
13. Concurrent autoimmune disease at risk for exacerbation with immunosuppression
reduction
14. Any untreated active infection including BK viremia >10^4 copies
15. Infection with human immunodeficiency virus (HIV)
16. Recent (within one year) or ongoing treatment for malignancy with the exception of:
• Non- melanomatous skin cancer definitively treated by local therapy, and
• Definitively treated carcinoma-in-situ of the cervix (Stage 0 cervical cancer)
17. Treatment or prophylaxis of COVID-19 with a monoclonal antibody product or
convalescent plasma within 6 months preceding enrollment, or
18. Any past or current medical problems, treatments, or findings which, in the opinion of
the investigator, may:
• pose additional risks from participation in the study,
• interfere with the candidate's ability to comply with study requirements, or
• impact the quality or interpretation of the data obtained from the study.
Complications of transplanted organs and tissue, Other immunodeficiencies, Other, Transplant, Kidney Transplant Recipients, Liver Transplant Recipients
Study of GS-1811 Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors
This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine
the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GS-1811 as
monotherapy and in combination with Zimberelimab in participants with advanced solid tumors.
This study will be conducted in 5 parts (Parts A, B, and E: monotherapy, Parts C and D:
combination therapy), in participants with advanced solid tumors who have received, been
intolerant to, or been ineligible for all treatments known to confer clinical benefit or in
participants with select solid tumors.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05007782
Show full eligibility criteria
Hide eligibility criteria
Key
Inclusion Criteria:
• Disease:
• Part A: Individuals with histologically or cytologically confirmed advanced solid
tumors who have received, been intolerant to, or been ineligible for all
treatment known to confer clinical benefit.
• Part B: Individuals with histologically or cytologically confirmed select
indications who have received, been intolerant to, or been ineligible for all
treatment known to confer clinical benefit.
• Part C: Individuals with histologically or cytologically confirmed advanced solid
tumors who have received, been intolerant to, or been ineligible for all
treatment known to confer clinical benefit or whose disease is indicated for
anti-PD-(L)1 monoclonal antibody monotherapy.
• Part D: Individuals with pathologically confirmed select advanced solid tumors.
• Part E: Individuals with pathologically confirmed select advanced solid tumors.
Participants must have received, have been intolerant to, or have been ineligible
for all treatment known to confer clinical benefit.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for
individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D and E.
• Adequate organ function.
• Male individuals and female individuals of childbearing potential who engage in
heterosexual intercourse must agree to use methods of contraception.
• Tissue requirement:
• Parts A, C, D and E: Must provide pre-treatment adequate tumor tissue sample
prior to enrolment.
• Part B: Must have fresh pre-treatment and on-treatment biopsy for biomarker
analysis.
Key
Exclusion Criteria:
• Concurrent anticancer treatment.
• Any anti-cancer therapy, whether investigational or approved, within protocol
specified time prior to initiation of study including: immunotherapy or biologic
therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14
days), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21
days).
• Any prior CCR8 directed therapy.
• Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell
transplantation. Exception: prior corneal transplant without requirement for systemic
immunosuppressive agents is allowed.
• Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected
carcinoma in situ, localized prostate cancer, or superficial bladder cancer after
undergoing potentially curative therapy with no evidence of disease. Individuals with
other previous malignancies are eligible if disease-free for > 2 years.
• History of intolerance, hypersensitivity, or treatment discontinuation due to severe
immune-related adverse events (irAEs) on prior immunotherapy.
• History of autoimmune disease or active autoimmune disease requiring systemic
treatment within 2 years.
• History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis
(excluding localized radiation pneumonitis).
• Active and clinically relevant bacterial, fungal, or viral infection that is not
controlled or requires IV antibiotics.
• Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human
immunodeficiency virus (HIV).
• Positive serum pregnancy test or breastfeeding female.
• Live vaccines within 30 days prior to first dose.
• Significant cardiovascular disease.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Advanced Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Study of DF1001 in Patients With Advanced Solid Tumors
DF1001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell
activation signals to specific receptors on cancer cells. The study will occur in two phases.
The first phase will be a dose escalation phase, enrolling patients with various types of
solid tumors that express human epidermal growth factor receptor 2 (HER2). The second phase
will include a dose expansion using the best dose selected from the first phase of the study.
Multiple cohorts will be opened with eligible patients having either HER2 activated non-small
cell lung cancer, hormone receptor (HR) positive HER2 negative metastatic breast cancer, or
HER2 positive metastatic breast cancer. DF1001-001 will be administered as monotherapy or in
combination; combinations are DF1001 + nivolumab, DF1001 + Nab paclitaxel, and DF1001 +
sacituzumab govitecan-hziy.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04143711
Show full eligibility criteria
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Inclusion Criteria:
General (applies to all cohorts)
1. Signed written informed consent.
2. Male or female patients aged ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry
and an estimated life expectancy of at least 3 months.
4. Baseline Left Ventricular Ejection Fraction (LVEF) ≥ 55% measured by echocardiography
(preferred) or multigated acquisition (MUGA) scan.
5. Adequate hematological function.
6. Adequate hepatic function.
7. Adequate renal function.
8. Effective contraception for women of child bearing potential (WOCBP) patients as
defined by World Health Organization (WHO) guidelines for 1 "highly effective" method
or 2 "effective" methods.
Inclusion Criteria:
NSCLC (HER2 Activated) Exploratory Efficacy Cohorts •Monotherapy and
Combination with Sacituzumab Govitecan-hziy.
1. Have progression of unresectable locally advanced or metastatic NSCLC after last
systemic therapy (as confirmed by investigator) or be intolerant of last systemic
therapy.
2. Have HER2 overexpression status (IHC 2+ or 3+), or ERBB2 amplification, or HER2
activating mutation
3. Have recurrent or progressive disease during or after platinum doublet-based
chemotherapy.
4. Have received and progressed on or after anti-PD-(L)1 therapy.
Inclusion Criteria:
Metastatic Breast Cancer (HR+/HER2-) Exploratory Efficacy Cohort -
Monotherapy and Combination with Sacituzumab Govitecan-hziy.
1. Documented evidence of HR+ metastatic breast cancer
2. Documented evidence of HER2- status.
3. Disease progression or recurrence after prior therapy.
Inclusion Criteria:
Metastatic Breast Cancer (HER2+) Exploratory Efficacy Cohorts -
Combination with Sacituzumab Govitecan-hziy
1. Have histologically confirmed HER2+ breast cancer.
2. Have received prior treatment with trastuzumab, pertuzumab, ado-trastuzumab emtansine
(T-DM1), or trastuzumab deruxtecan (T-DXd).
3. Have progression of unresectable locally advanced metastatic breast cancer after last
systemic therapy or be intolerant of last systemic therapy.
Inclusion Criteria:
Dose Escalation
1. Evidence of objective disease, but participation does not require a measurable lesion.
2. Locally advanced or metastatic solid tumors, for which no standard therapy exists, or
standard therapy has failed.
3. HER2 expression by immunohistochemistry and/or erbb2 amplification and/or erbb2
activating mutations.
Inclusion Criteria:
"3+3" Nivolumab Combination Cohort
1. Eligible to receive nivolumab per its label for a malignancy of epithelial origin; or
2. Have no standard therapy available, or standard therapy has failed, and must not have
received nivolumab prior to joining the study.
3. HER2 expression by immunohistochemistry and/or ebb2 amplification and/or erbb2
activating mutations must be documented on either archival tissue or fresh tumor
biopsy.
Inclusion Criteria:
"3+3" Nab paclitaxel Combination Cohort
1. Patients must be eligible for treatment with nab-paclitaxel per its label, or have no
standard therapy available, or standard therapy has failed.
2. HER2 expression by immunohistochemistry and/or erbb2 amplification and/or erbb2
activating mutations must be documented on either archival tissue or fresh tumor
biopsy.
Inclusion Criteria:
Safety/PK/PD Expansion Cohorts (Monotherapy and Combination Therapy).
1. Fresh tumor biopsy must be obtained during the screening window.
2. HER2 expression by immunohistochemistry (IHC).
3. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
Inclusion Criteria:
Urothelial Bladder Cancer Expansion Cohort(s).
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically or cytologically documented locally advanced or metastatic transitional
cell carcinoma of the urothelium (including renal pelvis, ureters, urinary urothelial,
urethra).
3. Patients must have received a platinum containing chemotherapy and an anti PD-1 or
anti PD-L1 for the treatment of urothelial bladder cancer.
Inclusion Criteria:
Breast Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1
2. Histologically documented (metastatic or locally advanced) breast cancer.
3. Absence of erbb2 amplification by ISH and/or HER2 IHC of 0, 1+, or 2+.
4. Patient must have progressed after one line of systemic chemotherapy.
Inclusion Criteria:
Breast Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1
2. Histologically documented (metastatic or locally advanced) breast cancer.
3. Erbb2 amplification by ISH and/or HER2 IHC of 3+, or 2+. If Herceptest score is 2+,
ISH results should demonstrate erbb2 amplification.
Inclusion Criteria:
Basket erbb2 amplified Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Documented history of erbb2 amplification.
3. Patients must have received at least one line of an approved or established therapy.
Inclusion Criteria:
Gastric Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) gastric cancer or cancer of the
gastro-esophageal junction.
3. Tumor must have been declared HER2 positive.
Inclusion Criteria:
Gastric Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) gastric cancer or cancer of the
gastro-esophageal junction.
3. Tumor must have been declared HER2 low; ISH non-amplified and/or HER2 IHC of 0, 1+ or
2+. If Herceptest score is 0, HER2 must be detected by IHC on at least 1+ of the tumor
cells.
Inclusion Criteria:
Esophageal Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) esophageal cancer.
3. Tumor must have been declared HER2 positive.
Inclusion Criteria:
Esophageal Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) esophageal cancer.
3. Tumor must have been declared HER2 low; ISH non-amplified and/or HER2 IHC of 0, 1+ or
2+. If Herceptest score is 0, HER2 must be detected by IHC on at least 1+ of the tumor
cells.
Inclusion Criteria:
Non-small Cell Lung Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or
recurrent disease that has been confirmed to have HER2 expression (at least 1+,
however, patients must not carry an erbb2 amplification) via archival or fresh biopsy
tissue prior to study enrollment.
3. Patients must have recurrent or progressive disease during or after platinum
doublet-based chemotherapy.
Inclusion Criteria:
Non-small Cell Lung Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or
recurrent disease that has been confirmed to have amplification of erbb2 via archival
or fresh biopsy tissue prior to study enrollment.
3. Patients must have recurrent or progressive disease during or after platinum
doublet-based chemotherapy.
Exclusion Criteria:
1. Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy [with the
exception of palliative bone directed radiotherapy], immune therapy, or cytokine
therapy except for erythropoietin), major surgery (excluding prior diagnostic biopsy),
concurrent systemic therapy with steroids or other immunosuppressive agents, or use of
any investigational drug within 28 days or 5 half-lives before the start of study
treatment. Note: Patients receiving bisphosphonates are eligible provided treatment
was initiated at least 14 days before the first dose of DF1001.
2. Previous malignant disease other than the target malignancy to be investigated in this
study within the last 3 years, with the exception of basal or squamous cell carcinoma
of the skin or cervical carcinoma in situ.
3. Rapidly progressive disease.
4. Active or history of central nervous system (CNS) metastases.
5. Receipt of any organ transplantation including autologous or allogeneic stem-cell
transplantation.
6. Significant acute or chronic infections (including historic positive test for human
immunodeficiency virus [HIV], or active or latent hepatitis B or active hepatitis C
tested during the screening window).
7. Preexisting autoimmune disease (except for patients with vitiligo) needing treatment
with systemic immunosuppressive agents for more than 28 days within the last 3 years
or clinically relevant immunodeficiencies (eg, dys-gammaglobulinemia or congenital
immunodeficiencies), or fever within 7 days of Day 1.
8. Known severe hypersensitivity reactions to mAbs (≥ Grade 3 NCI-CTCAE v5.0), any
history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partly
controlled asthma).
9. Persisting toxicity related to prior therapy > Grade 1 NCI-CTCAE v5.0, however
alopecia and sensory neuropathy ≤ Grade 2 is acceptable.
10. Pregnancy or lactation in females during the study.
11. Known alcohol or drug abuse.
12. Serious cardiac illness
13. NYHA III of IV heart failure or systolic dysfunction (LVEF < 55%)
14. High-risk uncontrolled arrhythmias ie, tachycardia with a heart rate > 100/min at rest
15. Significant ventricular arrhythmia (ventricular tachycardia) or higher-grade
Atrioventricular block (AV-block; second-degree AV-block Type 2 [Mobitz 2] or
third-degree AV-block)
16. Angina pectoris requiring anti-anginal medication
17. Clinically significant valvular heart disease
18. Evidence of transmural infarction on ECG
19. Poorly controlled hypertension (defined by: systolic > 180 mm Hg or diastolic > 100 mm
Hg)
20. Clinically relevant uncontrolled cardiac risk factors, clinically relevant pulmonary
disease or any clinically relevant medical condition in the opinion of the
Investigator that may limit participation in this study.
21. Severe dyspnea at rest due to complications of advanced malignancy or requiring
supplementary oxygen therapy.
22. All other significant diseases (e.g., inflammatory bowel disease), which, in the
opinion of the Investigator, might impair the patient's ability to participate
23. Any psychiatric condition that would prohibit the understanding or rendering of
informed consent.
24. Legal incapacity or limited legal capacity.
25. Incapable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol .
Solid Tumor, Adult, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)
A Phase 2 multi-center open-label basket trial of nab-sirolimus for adult and adolescent
patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or
TSC2 genes
Dustin Deming, MD
All
12 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05103358
Show full eligibility criteria
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Inclusion Criteria:
1. Patients must have a malignant solid tumor with a pathogenic inactivating TSC1 or TSC2
alteration. Genetic alterations should be identified using NGS in tumor tissue or
liquid biopsy).
• Patients will be enrolled after the central evaluation of NGS report confirms
eligibility.
2. Patients must have solid tumors that are metastatic or locally advanced where surgical
resection is not an option or likely to result in severe morbidity.
3. Patients must have received all standard therapies appropriate for their tumor type
and stage of disease or, in the opinion of the Investigator, the patient would be
unlikely to tolerate or derive clinically meaningful benefit from appropriate standard
of care therapy, or the patient has no satisfactory alternative treatments.
4. Patients must have 1 or more measurable target lesions by computed tomography (CT)
scan or magnetic resonance imaging (MRI) (RECIST v1.1).
5. Age: 12 years or older.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or Karnofsky
Performance Status (KPS) ≥80 or Lansky play-performance scale for pediatric patients
≥80.
7. Adequate liver function:
1. Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's
syndrome, then ≤3 × ULN)
2. Aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if attributable to liver
metastases)
8. Adequate renal function: creatinine clearance ≥30 mL/min, Cockcroft-Gault CCr =
((140-age) × weight[kg]) / (72 × SCr[mL/min]) × 0.85, if female
9. Adequate hematologic parameters:
1. Absolute neutrophil count (ANC) ≥1.0 × 109/L (growth factor support allowed)
2. Platelet count ≥100,000/mm3 (100 × 109/L) (transfusion and/or growth factor
support allowed)
3. Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed)
10. Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be ≤350
mg/dL.
11. Minimum of 4 weeks since any major surgery, completion of radiation, or completion of
prior systemic anticancer therapy, or at least 5 half-lives if the prior therapy is a
single agent small-molecule therapeutic, and adequately recovered from the acute
toxicities of any prior therapy, including neuropathy, to Grade ≤1.
12. Male or non-pregnant and non-breastfeeding female:
1. Females of childbearing potential must agree to use effective contraception or
abstinence without interruption from 28 days prior to starting investigational
product (IP) throughout 3 months after last dose of IP and have a negative serum
pregnancy test (beta human chorionic gonadotropin, β-hCG) result at screening and
agree to ongoing pregnancy testing during the course of the study, and after the
end of study treatment. A second form of birth control is required even if she
has had a tubal ligation.
2. Male patients must agree not to donate sperm and must practice abstinence or
agree to use a condom during sexual contact with a pregnant female or a female of
childbearing potential while participating in the study and throughout 3 months
after last dose of IP. A second form of birth control is required even if he has
undergone a successful vasectomy.
13. The patient or the patient's parent(s) or legal guardian(s) understand(s) and sign(s)
the informed consent.
14. Willingness and ability to comply with scheduled visits, laboratory tests, and other
study procedures.
Exclusion Criteria:
1. Prior treatment with an mTOR inhibitor, including nab-sirolimus.
2. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective
treatment, either ongoing or completed ≤7 days prior to enrollment.
3. Patients with primary brain tumors or PEComa.
4. Patients who have any severe and/or uncontrolled medical or psychiatric conditions or
other conditions that could affect their participation including:
1. Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal
cord compression, untreated brain metastases or symptomatic or unstable brain
metastases. Note: Patients with stable brain metastases (defined as asymptomatic
or no requirement for high-dose [defined as dexamethasone 10 mg daily or higher]
or increasing dose of systemic corticosteroids) and without imminent need of
radiation therapy are eligible. If applicable, patients must have completed brain
radiation therapy and recovered adequately from any associated toxicity and/or
complications prior to eligibility assessment. For patients who have received
prior radiation therapy, post-treatment MRI scan should show no increase in brain
lesion size/volume.
2. Unstable angina pectoris, symptomatic congestive heart failure (New York Heart
Association, NYHA class III or IV), myocardial infarction ≤6 months prior to
first study treatment, serious uncontrolled cardiac arrhythmia or any other
clinically significant cardiac disease.
3. Pre-existing severely impaired lung function. If a patient has a pre-existing
pulmonary condition, eligible patients should have a spirometry and diffusing
capacity for carbon monoxide (DLCO) that is >50% of the normal predicted value
and/or O2 saturation that is >88% at rest on room air (Note: spirometry and
pulmonary function tests [PFTs] not required to be performed unless clinically
indicated).
4. Nonmalignant medical illnesses that are uncontrolled or whose control may be
jeopardized by the treatment with the study therapy.
5. A history of malignancies other than the one under treatment unless the patient
is disease-free for more than 5 years from diagnosis. Note, controlled
non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental
prostate cancer, certain low grade hematologic malignancies (eg CLL, follicular
lymphoma, etc), or other adequately treated carcinoma-in-situ may be eligible,
after discussion with the medical monitor.
6. Uncontrolled hypertension (systolic blood pressure ≥160 mm-Hg and/or diastolic
blood pressure ≥100 mm Hg).
7. Patients with history of interstitial lung disease and/or pneumonitis, or
pulmonary hypertension.
8. Individuals with known human immunodeficiency virus (HIV) infection are excluded
from this study as combination antiretroviral therapy could potentially result in
significant pharmacokinetic interactions. In addition, these individuals are at
increased risk of serious infections due to the immunosuppressive effects of mTOR
inhibition.
9. Active Hepatitis B or Hepatitis C, with detectable viral load.
5. Regarding concomitant medications with significant CYP3A4 and P-gp interactions,
discontinuation of strong inhibitors (eg, ketoconazole, itraconazole, voriconazole,
erythromycin, clarithromycin, telithromycin, and others), strong inducers (eg,
rifampin, rifabutin), and known CYP3A4 substrates with a narrow therapeutic window
(eg, fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide,
quinidine, or terfenadine) is required at least 5 half lives prior to receiving the
first dose of nab-sirolimus, whichever is longer.
Tumor, Tumor, Solid, Metastasis, Metastatic Cancer, Cancer, Cancer Metastatic, Tumors, Neoplasms, Neoplasm Metastasis, Solid Tumor, Advanced Solid Tumor, Advanced Cancer, Malignant Solid Tumor, Malignant Solid Neoplasm, Malignant Neoplasm, Malignant Tumor, TSC, TSC1, TSC2, Metastatic Solid Tumor, Metastatic Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Lung, Melanoma/Skin cancer, Sarcoma, Uterus
The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study
This study aims to use clinical and biological characteristics of acute leukemias to screen
for patient eligibility for available pediatric leukemia sub-trials. Testing bone marrow and
blood from patients with leukemia that has come back after treatment or is difficult to treat
may provide information about the patient's leukemia that is important when deciding how to
best treat it, and may help doctors find better ways to diagnose and treat leukemia in
children, adolescents, and young adults.
Kenneth Desantes, M.D.
All
up to 22 Years old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04726241
Show full eligibility criteria
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Inclusion Criteria:
• Patients must be less than 22 years of age at the time of study enrollment
• Patient must have one of the following:
• Patient has known or suspected relapsed/refractory (including primary refractory)
AML
• This includes isolated myeloid sarcoma
• Patient has known or suspected relapsed/refractory (including primary refractory)
myeloid leukemia of Down syndrome
• Patient has known or suspected relapsed ALL that meets one of the following
criteria:
• Second or greater B-ALL medullary relapse, excluding KMT2Ar.
• Any first or greater B-ALL medullary relapse involving KMT2Ar.
• Any first or greater T-ALL medullary relapse with or without KMT2Ar.
• Patient has known or suspected relapsed/refractory (including primary refractory)
mixed phenotype acute leukemia (MPAL)
• Patient has known or suspected de novo or relapsed/refractory (including primary
refractory) treatment-related AML (t-AML) or treatment-related myelodysplastic
syndrome (t-MDS)
• Patient has known or suspected de novo or relapsed/refractory (including primary
refractory) myelodysplastic syndrome (MDS)
• Patient has known or suspected de novo or relapsed/refractory (including primary
refractory) juvenile myelomonocytic leukemia (JMML)
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia Post Cytotoxic Therapy, Juvenile Myelomonocytic Leukemia, Mixed Phenotype Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic Syndrome Post Cytotoxic Therapy, Myeloid Leukemia Associated With Down Syndrome, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Leukemia
Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Solid Tumors (MK-6482-016)
The purpose of this study is to determine the safety and efficacy of belzutifan in
combination with pembrolizumab and lenvatinib in multiple solid tumors including
hepatocellular carcinoma (HCC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma
(PDAC), biliary tract cancer (BTC), endometrial cancer (EC),and esophageal squamous cell
carcinoma (ESCC). There is no formal hypothesis testing in this study.
Nataliya Uboha, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04976634
Show full eligibility criteria
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Inclusion Criteria:
• Diagnosis of one of the following advanced (unresectable and/or metastatic) solid
tumors, documented by histopathology or cytopathology:
• Hepatocellular carcinoma (HCC)
• Colorectal cancer (CRC) (non-microsatellite instability-high
[non-MSI-H]/deficient mismatch repair [dMMR])
• Pancreatic ductal adenocarcinoma (PDAC).
• Biliary tract cancer (BTC) (includes intrahepatic, extrahepatic
cholangiocarcinoma [CCA] and gall bladder cancer)
• Endometrial cancer (EC)
• Esophageal squamous cell carcinoma (ESCC)
• Disease progression on or since the most recent treatment (does not apply to newly
diagnosed unresectable or metastatic HCC or EC).
• Measurable disease per RECIST v1.1 as assessed locally (by investigator) and verified
by BICR
• Submission of an archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion not previously irradiated
• Male participants are abstinent from heterosexual intercourse or agree to follow
contraceptive guidance during and for at least 7 days after last dose of study
intervention with belzutifan and lenvatinib
• Female participants are not pregnant or breastfeeding, not a woman of child-bearing
potential (WOCBP), or is a WOCBP and agrees to follow contraceptive guidance during
the intervention period and and for at least 120 days after the last dose of
pembrolizumab or for at least 30 days after last dose of lenvatinib or belzutifan,
whichever occurs last
• Adequate organ function
• Adequately controlled blood pressure with or without antihypertensive medications
• HCC Specific
Inclusion Criteria:
No prior systemic chemotherapy, including anti-VEGF
therapy, anti-programmed cell-death (PD-1)/PD-L1 or any systemic investigational
anticancer agents for advanced/unresectable HCC (1L)
• CRC ([non-MSI-H/dMMR) Specific
Inclusion Criteria:
Received at least 2 prior lines of
systemic therapy for unresectable or metastatic disease which includes
fluoropyrimidine, irinotecan and oxaliplatin
• PDAC Specific
Inclusion Criteria:
Prior therapy with at least 1 (platinum or
gemcitabine containing regimen) but no more than 2 prior systemic therapies for
unresectable or metastatic pancreatic cancer
• BTC Specific
Inclusion Criteria:
Received at least 1 prior line of systemic therapy
(containing gemcitabine or fluoropyrimidine) for unresectable or metastatic disease
• EC Specific
Inclusion Criteria:
Study treatment is for 1L therapy of EC and
participants should not have received prior systemic chemotherapy. Exception: May have
received 1 prior line of line of systemic platinum-based adjuvant and/or neoadjuvant
chemotherapy in the setting of a curative-intent resection, if the recurrence occurred
≥6 months after the last dose of chemotherapy or may have received prior radiation
with or without chemotherapy
• ESCC Specific
Inclusion Criteria:
Have experienced radiographic or clinical
progression on one prior line of standard systemic therapy (immune oncology (IO) naïve
participants) or an anti-PD-1/PD-L1 (IO resistant participants)
Exclusion Criteria:
• Unable to swallow orally administered medication or presence of a gastrointestinal
(GI) disorder that may affect study intervention absorption
• History of a second malignancy that is progressing or has required active treatment
within 3 years
• A pulse oximeter reading <92% at rest, or requirement of intermittent supplemental
oxygen/ chronic supplemental oxygen
• Presence of central nervous system (CNS) metastases and/or carcinomatous meningitis
• Clinically significant cardiovascular disease within 6 months of first dose of study
intervention
• Symptomatic pleural effusion, unless clinically stable after treatment
• Preexisting ≥ Grade 3 gastrointestinal (GI) or non-GI fistula
• Moderate to severe hepatic impairment
• Clinically significant history of bleeding within 3 months before screening
• Presence of serious active nonhealing wound/ulcer/bone fracture
• Requirement for hemodialysis or peritoneal dialysis
• History of human immunodeficiency virus (HIV) infection
• History of Hepatitis B or active Hepatis C virus infections. with exceptions for HCC
and BTC
• Prior therapy with a PD-1, anti-PD-L1, anti-PD-L2 agent, vascular endothelial growth
factor (VEGF) tyrosine kinase inhibitor (TKI) or hypoxia-inducible factor 2α (HIF-2α)
• Radiographic evidence of intratumoral cavitation, or invasion/infiltration of a major
blood vessel
• EC specific exclusion criteria: History of carcinosarcoma, endometrial leiomyosarcoma
or other high-grade sarcomas, or endometrial stromal sarcomas
• ESCC specific exclusion criteria: Has clinically apparent ascites or pleural effusion
or experienced weight loss >20% over approximately 3 months before first dose of study
therapy
A Study of Therapeutic Iobenguane (131-I) and Vorinostat for Recurrent or Progressive High-Risk Neuroblastoma Subjects (OPTIMUM)
The purpose of this study is to evaluate the efficacy and safety of 131I-MIBG in combination
with Vorinostat in patients with Recurrent or Progressive neuroblastoma
Kenneth Desantes, M.D.
All
1 Year and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03561259
Show full eligibility criteria
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Inclusion Criteria:
1. Subjects with a diagnosis of iobenguane avid, high-risk neuroblastoma based on Revised
INRC criteria at the time of study enrollment with recurrent or progressive disease at
any time prior to enrollment, regardless of overall response to frontline therapy,
where frontline therapy includes a minimum of 4 cycles of induction therapy at any
time prior to enrollment.
2. May have had prior 131I-MIBG therapy, provided:
1. It has been at least 6 months from the date of last 131I-MIBG ;
2. Response was other than progressive disease on first restaging after 131I-MIBG ;
3. Prior 131I-MIBG was given as monotherapy and not in combination with systemic
anticancer agents;
4. Cumulative lifetime dose of 131I-MIBG at enrollment does not exceed 18 mCi/kg.
3. All soft tissue lesions identified on CT/MRI scans must be iobenguane avid lesions on
an (123I)-iobenguane scan, or
1. any progressive non-iobenguane avid lesion is proven by biopsy to be a
non-neuroblastoma lesion.
2. any other non-avid lesion is comprised of a fibrotic or scarred mass as shown by
routine imaging and confirmed by the investigator.
4. Adequate cryopreserved autologous peripheral blood stem cells or bone marrow (at least
2 aliquots of 2.0 × 10exp6 CD34/kg at the time of study enrollment).
5. If a male, must agree to use an adequate contraception method as deemed appropriate by
the Investigator (e.g., vasectomy, condoms) or partner using effective contraception
and to not donate sperm during the study and for 90 days after receiving the last dose
of study drug.
6. If a female of childbearing potential, have a negative serum pregnancy test result
prior to each dosing and, if sexually active, be practicing an effective method of
birth control [e.g., intrauterine device, double-barrier method (i.e., diaphragm, or a
cervical cap) with intravaginal spermicidal foam, cream or gel], or male partner
sterilization throughout the study.
7. Age at study entry ≥1 year.
8. Previous platelet transfusions are permitted, as long as the subject has a platelet
count ≥50,000/μL without transfusion support for at least 1 week.
9. Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline.
10. An absolute neutrophil count ≥750/μL without growth factor for 5 days.
11. Liver function parameter results: total bilirubin ≤2 × upper limit of normal for age,
and Serum alanine aminotransferase (glutamic-pyruvic transaminase) and serum aspartate
aminotransferase (glutamic-oxaloacetic transaminase) ≤ 10 times the upper limit of
normal (for all sites, the upper limit of normal for alanine aminotransferase is
defined as 45 U/L).
12. Normal thyroid function as measured by T4 or TSH or have abnormal results that are not
considered clinically important by the Investigator or may be receiving levothyroxine.
13. Cardiac Function: shortening fraction of ≥ 27% by echocardiogram or ejection fraction
≥ 50% documented by echocardiogram or radionuclide angiogram within 1 month prior to
Visit 1 (Baseline).
14. Karnofsky Performance Status (for subjects >16 years of age) or the Lansky Performance
Status Performance Status (for subjects 1 to 16 years of age) ≥50%.
15. Full recovery from the toxic effects of any prior therapy.
16. Coagulation Function:
1. International Normalized Ratio (INR) < 1.5
2. Partial thromboplastin time (PTT) < 1.5 times upper limit of normal.
Exclusion Criteria:
1. Subjects within 5 half-lives after any antibody-based immunotherapy, or have not
recovered from effects of any biologic therapy.
2. Subjects <12 weeks after myeloablative therapy with autologous stem cell transplant.
3. Subjects who have had an allogeneic stem cell treatment less than 4 months from Visit
1 are excluded. Those who have received allogeneic stem cell treatment more than 4
months from Visit 1 must have recovered and have no active graft versus host disease
(GVHD) to be eligible.
4. Subjects must not have received radiation for a minimum of 2 weeks prior to study
enrollment. Subjects whose only site(s) of disease have been radiated are eligible as
long as the subject has MIBG avidity 2 weeks after completion of radiation. A minimum
of 12 weeks prior to study enrollment is required following prior large field
radiation therapy (ie, craniospinal, whole abdominal, total lung, > 50% marrow space)
5. History of total body irradiation.
6. Subjects do not have adequate renal function defined as GFR ≥ 70 mL/min/1.73 m2 either
by creatinine clearance or radioisotope direct measurement or by calculation with the
Schwartz formula
7. Subjects who are on hemodialysis.
8. Pregnancy or breastfeeding.
9. Significant active infections including active hepatitis B, or hepatitis C infection,
or known infection with human immunodeficiency virus (HIV) (testing for HIV is not
required prior to study entry).
10. Clinically important cardiac, pulmonary, and hepatic impairment.
11. Vorinostat treatment exclusion criteria (subjects, who meet any one of these criteria
and otherwise meet eligibility criteria, are still eligible for 131I-MIBG monotherapy)
1. Since valproic acid has HDAC inhibitory activity, patients must not have received
valproic acid within 30 days of study entry.
2. Since vorinostat may prolong the QT interval, patients must not be receiving
other medications known to prolong the QT interval at the time of study entry .
Pentamidine must not have been received within 1 week of study enrollment.
3. Patients with a history of deep venous thrombosis that was not associated with
the presence of a central venous catheter.
4. Patients who are receiving Coumadin.
Neuroblastoma, Neuroectodermal Tumors, 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, 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, Other Hematopoietic, 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, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus
First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Advanced Solid Tumor Patients and in Combination With Fulvestrant in Patients With Advanced Breast Cancer
This is an open-label, FIH study designed to evaluate the maximum tolerated dose, recommended
Phase 2 dose, safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic
activity of RLY-2608, in advanced solid tumor patients with a
Phosphatidylinositol-4,5-bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutation in
blood and/or tumor per local assessment. The study will evaluate RLY-2608 as a single agent
for patients with unresectable or metastatic solid tumors, RLY-2608 + fulvestrant and
RLY-2608 + fulvestrant + CDK4/6 inhibitor (palbociclib or ribociclib) combination arms for
patients with HR+ HER2- locally advanced or metastatic breast cancer. The RLY-2608 single
agent arm, RLY-2608 + fulvestrant combination arm, and triple combination arms will have 2
parts: a dose escalation (Part 1) and a dose expansion (Part 2).
Kari Wisinski, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05216432
Show full eligibility criteria
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Key Inclusion Criteria
Patient has ECOG performance status of 0-1
One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor per local
assessment
•Other potentially oncogenic PIK3CA mutations may be considered but must be approved by
the Sponsor prior to enrollment.
Part 1 •Ability to provide archived tumor tissue or be willing to undergo pretreatment
tumor biopsy to assess PIK3CA status retrospectively Part 2 •Submit tumor tissue prior to
study drug initiation for determination of PIK3CA mutation retrospectively.
Key Inclusion for RLY-2608 Single Agent Arm
• [For Part 1]: Evaluable disease per RECIST v1.1
• [For Part 2]: Measurable disease per RECIST v1.1
• Disease that is refractory to standard therapy, intolerant to standard therapy, or has
declined standard therapy.
• Part 1- histologically or cytologically confirmed diagnosis of unresectable or
metastatic solid tumor
• Part 2 •Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the
following tumor types:
Group 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group 3:
cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian, head
and neck squamous cell, and cervical cancers Group 5: unresectable or metastatic solid
tumors with PIK3CA double mutations
Key Inclusion for Combination Arms
• [For Part 1 and Part 2]: Evaluable disease per RECIST v1.1
• Male or female with histologically or cytologically confirmed diagnosis of HR+, HER2-
unresectable or metastatic breast cancer that is not amenable to curative therapy.
Females may be postmenopausal, premenopausal, or perimenopausal. Premenopausal or
perimenopausal females must have a histologically or cytologically confirmed diagnosis
of HR+ HER2- advanced or metastatic breast cancer that is not amenable to curative
therapy and must have been previously treated with GnRH agonist at least 4 weeks prior
to start of study drug
• [For Part 1 and Part 2]: Had previous treatment for advanced or metastatic breast
cancer with:
1. ≤1 line of chemotherapy,
2. ≥1 cyclin-dependent kinases (CDK) 4/6 inhibitor, and
3. ≥1 antiestrogen therapy including, but not limited to, selective
estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor
modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole,
anastrozole, exemestane), and
4. ≥1 PARP inhibitor, if appropriate, if documented germline BRCA1/2 mutation Note:
Systemic local, loco-regional, or adjuvant treatment is not to be included in
enumeration or previous treatment
[For RLY-2608 + fulvestrant arm; Part 2, Group 2]: Received prior treatment with a PI3Kα
inhibitor and discontinued the inhibitor due to intolerance and not disease progression,
where intolerance is defined as treatment discontinuation due to treatment related AE (eg.
hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction
and/or life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome.
Key Exclusion Criteria
Prior treatment with PI3Kα, AKT, or mTOR inhibitors (except for RLY-2608 + fulvestrant arm,
Part 2, Group 2).
Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose
≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%.
History of hypersensitivity to PI3K inhibitors. For combination arms only: hypersensitivity
to fulvestrant, palbociclib, and/or ribociclib, as appropriate for the combination.
For triple combination arms only: history of pneumonitis or interstitial lung disease.
For the single agent and combination arms other than with ribociclib: mean QT interval
corrected using Fridericia's formula (QTcF) >480 msec. For the combination arms with
ribociclib: mean QTcF ≥450 msec.
Patient has a history of prolonged QT syndrome or torsades de pointes. Patient has a
familial history of prolonged QT syndrome.
Clinically significant, uncontrolled cardiovascular disease CNS metastases or primary CNS
tumor that is associated with progressive neurologic symptoms
PIK3CA Mutation, Solid Tumor, Adult, HER2-negative Breast Cancer, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer, Unresectable Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)
TROPION-PanTumor03 will investigate the safety, tolerability, and anti-tumour activity of
Datopotamab Deruxtecan (Dato-DXd) as Monotherapy and in Combination with Anticancer Agents in
Patients with Advanced/Metastatic Solid Tumours.
Joshua Lang, Post Grad
All
18 Years to 130 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT05489211
Show full eligibility criteria
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Key
Inclusion Criteria:
• Male and female, ≥ 18 years
• Documented advanced or metastatic malignancy
• Eastern Cooperative Oncology Group performance status of 0 or 1 with no deterioration
over the 2 weeks prior to baseline or day of first dosing
• All participants must provide a tumour sample for tissue-based analysis
• At least 1 measurable lesion not previously irradiated, except Substudy 3 (Prostate
Cancer) which allows participants with non measurable bone metastatic disease
• Adequate bone marrow reserve and organ function
• Minimum life expectancy of 12 weeks
• At the time of screening, contraceptive use by men or women should be consistent with
local regulations regarding the methods of contraception for those participating in
clinical studies
• All women of childbearing potential must have a negative serum pregnancy test
documented during screening
• Female participants must be 1 year post-menopausal, surgically sterile, or using 1
highly effective form of birth control. Female participants must not donate, or
retrieve for their own use, ova at any time during this study
• Male participants who intend to be sexually active with a female partner of
childbearing potential must be surgically sterile, avoid intercourse, or use a highly
effective method of contraception. Male participants must not freeze or donate sperm
at any time during this study.
• Capable of giving signed informed consent
• Provision of signed and dated written optional genetic research informed consent prior
to collection of samples for optional genetic research that supports the Genomic
Initiative
Key
Exclusion Criteria:
• Any evidence of diseases which, in the investigator's opinion, makes it undesirable
for the participant to participate in the study or that would jeopardize compliance
with the protocol
• History of another primary malignancy except for adequately resected basal cell
carcinoma or in situ squamous cell carcinoma of the skin, or other solid malignancy
treated with curative intent
• Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not
yet improved
• Spinal cord compression or brain metastases unless treated
• Leptomeningeal carcinomatosis
• Clinically significant corneal disease
• Active hepatitis or uncontrolled hepatitis B or C virus infection
• Uncontrolled infection requiring IV antibiotics, antivirals or antifungals, for
example prodromal symptoms
• Known HIV infection that is not well controlled
• Active TB infection
• Significant cardiac diseases
• History of non-infectious Interstitial lung disease (ILD)/pneumonitis that required
steroids
• Has severe pulmonary function compromise
• Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout
period
• Receipt of live, attenuated vaccine within 30 days prior to the first dose of study
intervention
• Prior exposure to anticancer therapies without an adequate treatment washout period
prior to enrolment or any concurrent anticancer treatment
• Major surgical procedure or significant traumatic injury within ≤ 3 weeks of the first
dose of study intervention or an anticipated need for major surgery during the study
• Prior treatment with TROP2-directed Anti-drug antibody, ADC Antibody-drug conjugate
(ADCs), other ADCs with deruxtecan payload
• Severe hypersensitivity to monoclonal antibodies
• Pregnant, breastfeeding, planning to become pregnant
Esophagus, Stomach, Colon, Rectum, Other Digestive Organ, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Colon and Rectum, Gastrointestinal cancers, other, Genitourinary cancers, other, Uterus, Endometrial Cancer, Gastric Cancer, Metastatic Castration-resistant Prostate Cancer, Ovarian Cancer, Colorectal Cancer, Urothelial Cancer, Biliary Tract Cancer
Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery
This phase II trial tests whether nivolumab in combination with cabozantinib works in
patients with mucosal melanoma. Immunotherapy with monoclonal antibodies, such as nivolumab,
may help the body's immune system attack the cancer, and may interfere with the ability of
tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking
some of the enzymes needed for cell growth. It works by blocking the action of an abnormal
protein that signals tumor cells to multiply. This helps stop the spread of tumor cells.
Giving nivolumab in combination with cabozantinib could prevent cancer from returning.
Vincent Ma, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05111574
Show full eligibility criteria
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Inclusion Criteria:
• STEP 0 INCLUSION CRITERIA
• Histologically proven mucosal melanoma by local pathology
• Central PD-L1 tumor tissue submission
• STEP 1 INCLUSION CRITERIA
• Receipt of the central PD-L1 testing results available
• Disease status-Resected R0 or R1 disease patients. Patients eligible for randomization
have resected R0 or R1 disease (with negative margins or positive microscopic margins)
that must meet one of the following 4 criteria as defined below:
• Regional lymph node (LN) involvement; OR
• In-transit metastases/satellite primary disease; OR
• Single localized, primary disease meeting one of the following site-specific
requirements:
• Head/neck •Sinonasal (including nasopharynx): any primary lesion; Nasal or
oral cavity; pT4a or above, given slightly improved OS
• NOTE: Conjunctival: does not meet the qualification for eligibility
• Anorectal •any primary lesion
• Vaginal/cervical •any primary, as they have 5 year OS rates of 5-25
• Urinary tract •any primary urethral or bladder tumor
• Penile
• Vulvar- AJCC cutaneous stage IIB or higher
• Esophageal/gallbladder •any primary
• Locoregionally recurrent following prior resection, meeting at least one of the
above criteria
• In addition, patients must have undergone cross-sectional imaging of the brain,
chest, abdomen and pelvis with no evidence of distant metastatic disease
• Disease status-Non-resected R2 or metastatic disease patients
• Non-resected R2 or metastatic disease that is assessable and measurable
radiographically or by physical examination
• Prior Treatment:
• No prior systemic checkpoint inhibitor therapy of mucosal melanoma, including in
the adjuvant setting, is allowed. Prior adjuvant chemotherapy or interferon is
allowed.
• No other active, concurrent malignancy that requires ongoing systemic treatment
or interferes with radiographic assessment of melanoma response as determined by
the investigator. Exceptions may allow for adjuvant no evidence of disease (NED)
cancers undergoing hormone based therapy may be eligible pending the other
eligibility criteria are met and the principal investigator (PI) affirms the
hormonal agent would not change the melanoma response.
• Any radiation must have completed 28 days prior to randomization and the patient
must have adequately recovered from its effects.
• For resectable patients only: Surgery must have completed 28 days prior to
randomization.
• For resectable patients only: Surgery must have completed no more than 84 days
prior to randomization.
• Not pregnant and not nursing, because this study has an agent that has known
genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing
potential only, a negative pregnancy test done =< 7 days prior to registration is
required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) >=
50mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Albumin >= 2.8 g/dL
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit
of normal (ULN)
• No cardiovascular disease, including:
• No history of acute coronary syndromes (including myocardial infarction and
unstable angina), coronary artery bypass graft (CABG) coronary angioplasty, or
stenting within 6 months prior to study entry.
• No history of current class II or higher congestive heart failure as defined by
the New York Heart Association (NYHA) functional classification system.
• No refractory hypertension defined as a blood pressure of systolic > 140 mmHg
and/or diastolic > 90 mmHg despite adequate attempts at anti-hypertensive
therapy.
• No history of myocarditis.
• No history of syncope of cardiovascular etiology, uncontrolled cardiac
arrhythmia, history of Mobitz II second degree or third degree heart block
without a permanent pacemaker in Association (NYHA) class II to IV heart failure,
or stroke/transient ischemic attack (TIA) within the past 3 months.
• No corrected QT interval by Fridericia's formula (QTcF) > 500 msec. Note: if
initial QTcF is found to be > 500 ms, two additional EKGs separated by at least 3
minutes should be performed. If the average of these three consecutive results
for QTcF is =< 500 ms, the subject meets eligibility in this regard.
• No underlying hematologic issues, including:
• Congenital bleeding diathesis
• Gastrointestinal (GI) bleeding requiring intervention within the past 6 months,
unless directly related to mucosal melanoma
• Active hemoptysis within 42 days prior to study enrollment.
• Active tumor lesions with cavitations or tumor lesions which invade, encase, or
abut major blood vessels. The anatomic location and characteristics of primary
tumors or metastases as well as the medical history should be carefully reviewed
in the selection of subjects for treatment with cabozantinib/placebo.
• Pulmonary emboli or deep vein thromboses (DVT) that require an active
anticoagulation regimen.
• No known or suspected history of cytopenia (low white blood cell [WBC],
hemoglobin or platelet count) of greater than 3 months duration with an unknown
cause, myelodysplastic syndrome, or hematologic malignancies.
• No clinical, laboratory or radiographic evidence of an active bacterial, fungal, or
viral infection requiring treatment at the time of pre-registration (e.g., active
symptoms of COVID-19 infection or a post-infectious symptomatic autoimmune syndrome,
serious bacterial infections requiring antibiotics).
• No known or suspected gastrointestinal disorder affecting absorption of oral
medications.
• Comorbid conditions:
• No active autoimmune disease or any condition requiring systemic treatment with
either corticosteroids (> 10 mg daily of prednisone equivalents) or other
immunosuppressive medications within 14 days of study drug administration.
Inhaled or topical steroids and adrenal replacement doses > 10 mg daily
prednisone equivalents are permitted in the absence of active autoimmune disease.
• No history of autoimmune motor neuropathy (e.g., Guillain-Barre syndrome,
myasthenia gravis) or non-infectious pneumonitis.
• No history of severe allergic reactions to an unknown allergen or any components
of the study drugs or its excipients.
• No history of gastrointestinal perforation or abdominal fistula.
• No clinically suspected central nervous system (CNS) (leptomeningeal or
parenchymal) metastases. Patients with a history of CNS metastasis(s) will be
allowed as long as
• The metastatic site(s) were adequately treated as demonstrated by clinical
and radiographic improvement, AND
• The patient has recovered from the intervention (no residual adverse events
> Common Terminology Criteria for Adverse Events [CTCAE] grade 1), AND
• The patient has remained without occurrence of new or worsening CNS symptoms
for a period of 28 days prior to enrollment.
• No history of seizure or any condition that may increase the patient's seizure
risk (e.g., prior cortical stroke, significant brain trauma) within 2 years.
• No clinically active or chronic liver disease resulting in moderate/severe
hepatic impairment (Child-Pugh class B or C), ascites, coagulopathy or bleeding
due to liver dysfunction.
• No untreated spinal cord compression or evidence of spinal metastases with a risk
of impending fracture or spinal cord compression. Spinal metastases must have
completed planned radiation or surgical therapy prior to registration.
• Concomitant medications:
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on
this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 5
days prior to the start of study treatment.
• Chronic concomitant treatment with strong CYP3A4 inducers is not allowed.
Patients must discontinue the drug 5 days prior to the start of study treatment.
Melanoma, Skin, Melanoma/Skin cancer, Anal Melanoma, Bladder Melanoma, Cervical Melanoma, Esophageal Melanoma, Gallbladder Melanoma, Mucosal Melanoma, Mucosal Melanoma of the Head and Neck, Mucosal Melanoma of the Urinary System, Nasopharyngeal Melanoma, Oral Cavity Mucosal Melanoma, Penile Mucosal Melanoma, Rectal Melanoma, Recurrent Mucosal Melanoma, Sinonasal Mucosal Melanoma, Stage II Vulvar Cancer AJCC v8, Stage III Vulvar Cancer AJCC v8, Stage IV Vulvar Cancer AJCC v8, Urethral Melanoma, Vaginal Melanoma, Vulvar Melanoma
Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma
Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase
III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma
(VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine
and dactinomycin (VA) and examines the use of centralized molecular risk stratification in
the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients
with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with
VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment.
Finally, this study examines the effect of therapy intensification in patients who have RMS
cancer with DNA mutations to see if their outcomes can be improved.
Kenneth Desantes, M.D.
All
up to 21 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05304585
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Inclusion Criteria:
• All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular
Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032
(this trial).
• Patients must be =< 21 years at the time of enrollment.
• Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle
cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS)
(institutional FOXO1 fusion results are acceptable). RMS types included under ERMS
include those classified in the 1995 International Classification of Rhabdomyosarcoma
(ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified
in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and
botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical
spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment
in APEC14B1 is required for all patients.
• All patients will be evaluated for stage and clinical group. Note that clinical
group designation assigned at the time of enrollment on study remains unchanged
regardless of any second-look operation that may be performed.
• Patients will be eligible for the very low-risk stratum (Regimen VA) if they
have Stage 1, CG I disease.
• Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they
have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III
(orbit only) disease.
• Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling
(SIRLNS) is required for all patients >= 10 years of age with paratesticular
tumors who do not have gross nodal involvement on imaging.
• Extremity Tumors: Regional lymph node sampling is required for histologic
evaluation in patients with extremity tumors.
• Clinically or radiographically enlarged nodes must be sampled for histologic
evaluation.
• Patients must have a Lansky (for patients =< 16 years of age) or Karnofsky (for
patients > 16 years of age) performance status score of >= 50. Patients who are unable
to walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing performance score.
• Peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to
enrollment).
• Platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to
enrollment).
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine (within 7 days prior to enrollment) based on
age/gender as follows:
• Age: 1 month to < 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4
(female)
• Age: 6 months to < 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5
(female)
• Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female)
• Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female)
• Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female)
• Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2
(female)
• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4
(female)
• Age >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment), and
• If there is evidence of biliary obstruction by the tumor, then the total
bilirubin must be < 3 x ULN for age.
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L.
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L (within 7 days prior to enrollment).
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
Exclusion Criteria:
• Patients who have received prior chemotherapy and/or radiation therapy for cancer
prior to enrollment. Surgical resection alone of previous cancer(s) is permitted.
• Patients who have received chemotherapy or radiation for non-malignant conditions
(e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for
non-malignant conditions prior to starting protocol therapy.
• Vincristine is sensitive substrate of the CYP450 3A4 isozyme. Patients must not have
received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7
days prior to study enrollment.
• Patients unable to undergo radiation therapy, if necessary, as specified in the
protocol.
• Evidence of uncontrolled infection.
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential.
• Lactating females who plan to breastfeed their infants.
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation.
Embryonal Rhabdomyosarcoma, Fusion-Negative Alveolar Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Soft Tissue, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma
Phase 2 Study of DKN-01 in Colorectal Cancer (DeFianCe)
This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to
evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of
care (SOC) [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced CRC
patients.
Dustin Deming, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05480306
Show full eligibility criteria
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Adult patients with advanced CRC with measurable disease (RECIST v1.1) who have
radiographically progressed during or following one line of systemic treatment will be
enrolled in the study.
Inclusion Criteria:
Patients meeting all of the following criteria will be considered eligible for study entry:
1. Disease progression following first-line systemic therapy with any
fluoropyrimidine-based regimen for advanced disease (except FOLFOXIRI, see exclusion
criteria).
• Patients may have received prior neoadjuvant or adjuvant therapy which could have
included irinotecan or oxaliplatin. If progression has occurred within 12 months from
last dose of neoadjuvant or adjuvant treatment, this regimen will be considered as the
one line of systemic therapy for advanced disease.
• If assigned to receive FOLFIRI, patient may have received no prior irinotecan as
part of first-line systemic therapy.
• If assigned to receive FOLFOX, patient may have received no prior oxaliplatin as
part of first line systemic therapy.
• Prior treatment with an anti-VEGF or anti-EGFR therapy is allowed as first-line
and/or maintenance systemic therapy.
2. Able to provide written informed consent for any study specific procedures.
3. One or more tumors measurable on radiographic imaging as defined by RECIST 1.1
4. Sufficient tumor tissue for mandatory pre-treatment evaluation (fresh biopsy
[preferred], or archived tissue block specimen).
5. ECOG performance status ≤1 within 7 days of first dose of study drug. Acceptable
liver, renal, hematologic, and coagulation function
6. Females of childbearing potential and male partners of female patients must agree to
use adequate contraception during the study and for 6 months after their last dose of
study drug
Exclusion Criteria:
Patients meeting any of the following criteria are not eligible for study entry:
1. Diagnosis of Microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR)
and/or BRAF V600E mutation positive colorectal cancer.
2. Prior therapy with an anti-DKK1, FOLFOXIRI, PD-1, anti-PD-L1, anti-PD-L-2 or any other
antibody or drug specifically targeting T-cell co-stimulation or coinhibitory
checkpoint.
3. Systemic anti-cancer therapy within 28 days prior to first dose of study drug.
4. Major surgery within 28 days prior to first dose of study drug.
5. Prior radiation therapy within 14 days prior to first dose of study drug.
6. Active leptomeningeal disease or uncontrolled brain metastases.
7. Any active cancer ≤ 2 years before first dose of study drug with the exception of
cancer for this study.
8. New York Heart Association Class III or IV cardiac disease, myocardial infarction
within the past 6 months, or unstable arrhythmia.
9. Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital
long QT syndrome.
10. Active, uncontrolled bacterial, viral, or fungal infections, within 14 days of study
entry requiring systemic therapy.
11. Serious nonmalignant disease
12. Pregnant or nursing.
13. History of osteonecrosis of the hip or have evidence of structural bone abnormalities
in the proximal femur on MRI scan that are symptomatic and clinically significant.
14. Known osteoblastic bony metastasis.
15. Major surgery 28 days prior to study entry.
16. Prior radiation therapy within 14 days prior to study entry.
17. Significant allergy to a pharmaceutical therapy that, in the opinion of the
Investigator, poses an increased risk to the patient.
18. Active substance abuse.
19. Known dihydropyrimidine dehydrogenase deficiency.
20. Administration of a live vaccine within 28 days before first dose of study drug
Colorectal Cancer, Colorectal Adenocarcinoma, Colo-rectal Cancer, Colorectal Cancer Metastatic, Colon, Rectum, Colon and Rectum
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
Show full eligibility criteria
Hide eligibility criteria
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
This Study Aims to Find the Best Dose of BI 907828 (Brigimadlin) in Patients With Different Types of Advanced Cancer (Solid Tumors)
This study is open to adults with different types of advanced cancer (solid tumors). The
purpose of this study is to find out the most suitable dose of BI 907828 (brigimadlin) the
participants can tolerate. The most suitable dose is used in the second part to find out
whether brigimadlin makes tumors shrink.
In this study, brigimadlin is given to humans for the first time. Brigimadlin is a so-called
MDM2 inhibitor that is being developed to treat cancer. Brigimadlin is taken as a tablet.
Participants either take a dose of brigimadlin on one day every 3 weeks or on two days every
4 weeks.
The participants are in the study for as long as they benefit from and can tolerate
treatment. The doctors regularly check the participants' general health during the study.
Jeremy Kratz, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT03449381
Show full eligibility criteria
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Inclusion Criteria:
• Provision of signed and dated, written informed consent form ICF in accordance with
ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or
analyses.
• Pathologically documented, advanced solid tumors.
• Patients fulfilling one or more of the following criteria:
• Radiologically documented disease progression or relapse
• Patients who are not eligible to receive standard of care treatments, and for
whom no proven treatments exist.
• Patients with MDM2 amplified sarcomas who require first line treatment (for Ph
Ib/dose expansion •Cohort 1 only).
• Patients with MDM2 amplified sarcomas may fulfil any one of the above three criteria
to be considered eligible.
• Phase Ia (dose escalation) only:
• Patient has a tumor with either a known TP53 wild type status, or unknown TP53 status,
and regardless of MDM2 amplification status, at the time of study entry.
• Phase Ib (expansion phase) only:
• Cohort 1: TP53 wt and MDM2-amplified sarcoma with advanced/metastatic disease at any
line of therapy. If TP53 status is not available during screening, the patient may be
included with unknown TP53 status if a tissue sample is submitted for central
laboratory assessment. If TP53 status cannot be evaluated, the patient may be included
if agreed between the Investigator and Sponsor.
• Cohort 2: TP53 wt and MDM2- amplified NSCLC, urothelial, gastric, biliary tract
(including cholangiocarcinoma, intra- and extrahepatic biliary tree, gall blander and
ampulla of vater) or pancreatic solidPDAC tumors who have had at least one previous
line of therapy for advanced/metastatic disease. If TP53 status cannot be evaluated
the patient may be included if agreed between the Investigator and Sponsor
• Phase Ia (dose escalation) only:
• Patient with either measurable or non-measurable disease.
• Non-evaluable disease allowed.
• Phase Ib (expansion phase) only:
• At least one target lesion that can be accurately measured per RECIST v.1.1.
• Phase Ia:
• Patient must be willing to undergo blood sampling for PK, pharmacodynamic, biomarker,
and PGx analyses.
• Phase Ib:
• Patient must be willing to undergo tumor biopsy sampling for pharmacodynamic analyses
and blood sampling for PK, pharmacodynamics, and biomarker analyses.
• Willingness to provide a fresh tumor tissue sample obtained after relapse/ progression
during or after prior therapy. In case a fresh biopsy cannot be obtained (e.g.
inaccessible lesions or patient safety concern), an archived specimen, collected
before screening within 12 months of enrollment, may be submitted. If these
requirements cannot be met, then the patient may be allowed to enter the study at
Sponsor discretion, after agreement between the Investigator and Sponsor.
• Further inclusion criteria apply
Exclusion Criteria:
• Previous administration of BI 907828 (brigimadlin) or any other MDM2-p53 or MDMX
(MDM4)-p53 antagonist.
• Known TP53 mutant tumor.
• Symptomatic metastases from non-brain tumors. Note: Patients with previously treated
brain metastases may participate provided they are stable, without evidence of
progression by imaging (using the identical imaging modality for each assessment,
either MRI or computed tomography (CT) scan), for at least four weeks prior to the
first dose of trial treatment, and any neurologic symptoms have returned to baseline;
have no evidence of new or enlarging brain metastases. Patients on corticosteroids
must have a stable dose for at least 5 days prior to baseline MRI.
• Patients with history of bleeding diathesis.
• Major surgery (major according to the Investigator's assessment) performed within 12
weeks prior to start of study treatment, or planned within 12 months after screening
(e.g. hip replacement).
• Any other documented active or suspected malignancy or history of malignancy within 3
years prior to screening, except appropriately treated basal cell carcinoma of the
skin or in situ carcinoma of uterine cervix, or other local tumors considered cured by
local treatment.
• Patients who must or wish to continue the intake of restricted medications or any drug
considered likely to interfere with the safe conduct of the trial.
• Further exclusion criteria apply.
Neoplasms, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Strata PATH™ (Precision Indications for Approved Therapies) (Strata PATH)
StrataPATH™ is a non-randomized, open-label trial designed to explore efficacy and safety of
multiple FDA-approved and commercially available cancer therapies in new, biomarker-guided
patient populations.
Mark Burkard, MD, PhD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05097599
Show full eligibility criteria
Hide eligibility criteria
To be eligible to participate in this study, an individual must meet each of the criterion
below and the criteria indicated in the selected biomarker/drug cohort appendix:
1. Male or female ≥18 years of age.
2. Pathologically confirmed solid tumor
3. Participants must be able to follow study visit schedule and willing to provide up to
20 mL of peripheral blood samples at the indicated time points
4. CGP results need to be from a test conducted in a CLIA approved laboratory and
archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue is required for
confirmatory testing of non-Strata test results unless otherwise indicated within the
cohort-specific protocol criteria.
5. Biomarker positive for the defined cohort
6. For individuals with non-primary, treated or stable brain metastases: No evidence of
progression (defined as no radiographic evidence of progression) for at least 4 weeks
prior to consent.
7. Adequate bone marrow, organ function & laboratory parameters as determined by the
treating physician unless otherwise indicated within the cohort-specific protocol
criteria.
8. Adequate cardiac function: 1) Left ventricular ejection fraction (LVEF) ≥ 50% and 2)
QTc interval ≤ 470 ms (females) or ≤ 450 ms (males) average preferred.
An individual who meets any of the following criteria will be excluded from participation
in this study:
1. Receiving another cancer treatment
2. Major surgery within 4 weeks prior to study entry
3. Has received a systemic cancer treatment within 3 weeks of first study dose
4. Individuals with a history of a second malignancy are ineligible except for the
following circumstances. Individuals with a history of other malignancies are eligible
if they have been disease-free for at least 3 years or are deemed by the investigator
to be at low risk for recurrence of that malignancy. Individuals with the following
cancers that have been diagnosed and treated within the past 3 years are eligible:
cervical/prostate carcinoma in situ, superficial bladder cancer, non-melanoma cancer
of the skin. Patients with other cancers diagnosed within the past 3 years and felt to
be at low risk of recurrence should be discussed with the study principal investigator
to determine eligibility.
5. Participant has primary central nervous system tumor.
6. A woman of childbearing potential who has a positive urine pregnancy test (within 72
hours) prior to treatment. If the urine test is positive or cannot be confirmed as
negative, a serum pregnancy test will be required.
7. Females who are pregnant or nursing or plan to become pregnant or anyone unwilling to
use contraception for the duration of treatment.
8. Ongoing toxicity of CTCAE grade >2, other than peripheral neuropathy, related to
anticancer therapy that was completed within 4 weeks of consent.
9. Ongoing peripheral neuropathy of CTCAE grade >3.
10. History of stroke including transient ischemic attack (TIA) or acute myocardial
infarction within 6 months of consent.
11. Participant has a known history of human immunodeficiency virus (HIV), Hepatitis B or
known active Hepatitis C virus infection.
12. Medical condition that would place the patient at risk as a result of blood donation,
such as bleeding disorder.
13. Any other clinically significant medical condition that, in the opinion of the
treating physician, makes participation undesirable, including but not limited to
ongoing or active infection, significant uncontrolled hypertension, or severe
psychiatric illness.
Cancer, Advanced Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, 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
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
Malignant Solid Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
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
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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.
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
Synovial Sarcoma, Malignant Peripheral Nerve Sheath Tumor (MPNST), Neuroblastoma, Osteosarcoma, 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
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
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
Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical
trials to study cancer treatment directed by genetic testing. Patients with solid tumors that
have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places
in the body (advanced) and have progressed on at least one line of standard systemic therapy
or have no standard treatment that has been shown to prolong overall survival may be
candidates for these trials. Genetic tests look at the unique genetic material (genes) of
patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may
benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed
to match patients to a treatment that may work to control their tumor and may help doctors
plan better treatment for patients with locally advanced or advanced solid tumors.
Nataliya Uboha, MD
All
Not specified
Phase 2
This study is NOT accepting healthy volunteers
NCT05564377
Show full eligibility criteria
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Inclusion Criteria:
• Patient must have measurable disease
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
between 0-2 OR patient must have Lansky performance status of >= 50% or Karnofsky
performance status of >= 50%
• Patient must be deemed potentially eligible for a ComboMATCH Treatment Trial as
assessed by the enrolling provider
• All patients must have sequencing results available from a National Cancer Institute
(NCI) credentialed Designated Laboratory (DL)
• Patients must have locally advanced or advanced histologically documented solid tumors
requiring therapy and meet one of the following criteria:
• Patients must have progressed on at least one line of standard systemic therapy
OR
• Patients whose disease has no standard treatment that has been shown to prolong
overall survival
• Patient must meet one of the following requirements:
• Patients 18 years and older who have tumor amenable to minimal risk image-guided
or direct vision biopsy and must be willing and able to undergo a tumor biopsy to
obtain samples for research if the patient is to enroll in a ComboMATCH treatment
trial OR
• Patients 18 years and older who do not have disease that is biopsiable at minimal
risk to the patient must confirm availability of an archival tumor tissue
specimen for submission for research if the patient enrolls to a ComboMATCH
Treatment Trial. This tumor tissue must meet the following criteria:
• Tissue must have been collected within 12 months prior to registration to
the EAY191 Registration Trial
• Patient must not have had a Response Evaluation Criteria in Solid Tumors
(RECIST) response (complete response [CR] or partial response [PR]) to any
intervening therapy after collection of the tissue
• Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be
available OR
• Patients under 18 years old must confirm availability of an archival tumor tissue
specimen for submission for research if patient enrolls to a ComboMATCH Treatment
Trial. This tumor tissue must meet the following criteria:
• Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be
available
• NOTE: See specific ComboMATCH Treatment Trial protocol for tissue collection and
management instructions. Performance of the mandatory research biopsy or
submission of pre-trial formalin-fixed paraffin-embedded (FFPE) and collection
and submission of the blood specimens for the integrated studies will be
performed under the consent authority of the specific treatment trial protocol to
which the patient is registered. No procedures to collect specimens for research
only are to be performed for patients registered to the EAY191 Registration Trial
only
• NOTE: Each ComboMATCH Treatment Trial contains specific eligibility criteria. If
patient is found to not be eligible for the assigned ComboMATCH Treatment Trial,
indication of ineligibility will trigger re-evaluation and potential assignment to
another Treatment Trial
Advanced Malignant Solid Neoplasm, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Locally Advanced Malignant Solid Neoplasm, Malignant Female Reproductive System Neoplasm, Metastatic HER2-Negative Breast Carcinoma, Metastatic Malignant Solid Neoplasm, Recurrent Endometrial Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Malignant Female Reproductive System Neoplasm, Recurrent Malignant Solid Neoplasm, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma, Unresectable HER2-Negative Breast Carcinoma, Unresectable Malignant Solid Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Study of Chemotherapy Plus Ipatasertib for People With Solid Tumors With AKT Mutations, A ComboMATCH Treatment Trial
This phase II ComboMATCH treatment trial tests the usual treatment of chemotherapy
(paclitaxel) plus ipatasertib in patients with solid tumor cancers that that cannot be
removed by surgery (unresectable), has spread to nearby tissue or lymph nodes (locally
advanced) or from where it first started (primary site) to other places in the body
(metastatic), and has an AKT genetic change. Chemotherapy drugs, such as paclitaxel, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Targeted therapy, such as
Ipatasertib, may stop the growth of tumor cells by blocking some of the enzymes needed for
cell growth. The addition of ipatasertib to paclitaxel in solid tumors with an AKT genetic
change could increase the percentage of tumors that shrink as well as lengthen the time that
the tumors remain stable (without progression). Researchers hope to learn if paclitaxel plus
ipatasertib will shrink this type of cancer or stop its growth.
Nataliya Uboha, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05554380
Show full eligibility criteria
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Inclusion Criteria:
• Patient must have enrolled onto EAY191 and must have been given a treatment assignment
to ComboMATCH to EAY191-S3 based on the presence of an actionable mutation as defined
in EAY191
• GENERAL COMBOMATCH EAY191 REGISTRATION INCLUSION CRITERIA:
• Participants must be enrolled on the ComboMATCH Master Registration Trial EAY191
• Participants must have an activating AKT mutation (a known mutation in AKT1, AKT2, or
AKT3, a single nucleotide variant, insertion, or deletion) as determined by the
ComboMATCH screening assessment
• GENERAL COMBOMATCH EAY191 REGISTRATION EXCLUSION CRITERIA:
• Participants must not have an activating KRAS, NRAS, HRAS, or BRAF mutation (a single
nucleotide variant, insertion, or deletion) as determined by the ComboMATCH screening
assessment
• Participants must have disease that can be safely biopsied and agree to a
pre-treatment biopsy or have archival tissue available from within 12 months prior to
the date of registration on the ComboMATCH Registration Trial (EAY191)
• Participants must have a histologically confirmed non-breast solid malignancy
• Participants must have locally advanced, unresectable, or metastatic disease in the
opinion of the treating investigator
• Participants must have measurable disease documented by CT or MRI. Measurable disease
must be assessed within 28 days prior to registration. Non-measurable disease must be
assessed within 42 days prior to registration. The CT from a combined positron
emission tomography (PET)/CT may be used only if it is of diagnostic quality. All
known sites of disease must be assessed and documented on the Baseline Tumor
Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
Participants whose only measurable disease is within a previous radiation therapy port
must demonstrate clearly progressive disease (in the opinion of the treating
investigator) prior to registration
• Participants with known brain metastases must have a CT/MRI scan to evaluate for
central nervous system (CNS) disease and show no evidence of progression within 42
days prior to registration
• Participants must have completed any CNS-directed therapy and/or local therapy for
spinal cord compression at least 28 days prior to registration
• Participants must not have spinal cord compression or brain metastases unless: (1)
metastases have been locally treated and have remained clinically controlled and
asymptomatic for at least 14 days prior to registration, AND (2) participant has no
residual neurological dysfunction and has been off corticosteroids for at least 24
hours prior to registration
• Participants must not have leptomeningeal disease
• Participants must have progressed within 6 months of taxane-based therapy in the
neoadjuvant/adjuvant or metastatic setting
• Participants must not have received any prior AKT inhibitor (e.g., capivasertib or
ipatasertib); prior PI3K/mTOR inhibitor is acceptable
• Participants must not be planning to receive any concurrent chemotherapy,
immunotherapy, biologic, radiation, or hormonal therapy for cancer treatment while
receiving treatment on this study
• Participants must be >= 18 years of age
• Participants must be able to swallow oral medications whole
• Participants must have a pre-study history and physical exam done within 28 days prior
to registration
• Participants must have a Zubrod performance status of 0-2 within 28 days prior to
registration
• Participants must have adverse events resolved =< grade 1 related to any prior
therapy, except alopecia within 14 days prior to registration
• Participants with neuropathy must have resolved to < grade 2 within 14 days prior to
registration
• Leukocytes >= 3 x 10^3/uL (within 28 days prior to registration)
• Absolute neutrophil count >= 1.5 x 10^3/uL (within 28 days prior to registration)
• Platelets >= 100 x 10^3/uL (within 28 days prior to registration)
• Total bilirubin =< institutional upper limit of normal (ULN) unless history of
Gilbert's disease. Participants with history of Gilbert's disease must have total
bilirubin =< 5 x institutional ULN (within 28 days prior to registration)
• Aspartate aminotransferase (AST) & alanine aminotransferase (ALT) =< 3 x institutional
ULN (within 28 days prior to registration)
• Participants must have adequate cardiac function, class IIB (2B) or better.
Participants with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification
• Participants must have a measured OR calculated creatinine clearance >= 50 mL/min
using the following Cockcroft-Gault formula. This specimen must have been drawn within
28 days prior to registration
• Participants with known human immunodeficiency virus (HIV)-infection must be receiving
anti-retroviral therapy and have an undetectable viral load test on the most recent
test results obtained within 6 months prior to registration
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have
undetectable HBV viral load on suppressive therapy within 28 days prior to
registration
• Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured. Participants with HCV infection who are currently on treatment must
have an undetectable HCV viral load within 28 days prior to registration
• Participants must have an electrocardiography (ECG) performed (if clinically indicated
with a corrected QTc interval of =< 470 msec) within 28 days prior to registration
• Participants must not have a history of allergic reactions attributed to compounds of
similar chemical or biologic composition to ipatasertib and/or paclitaxel
• Participants must not have an active small/large bowel inflammation such as ulcerative
colitis or Crohn's disease
• Participants must not have grade 2 or higher uncontrolled intercurrent illness
• NOTE: To receive an agent, participant must not have any uncontrolled
intercurrent illness requiring antibiotic/antiviral/antifungal therapy or
interventional procedures. Participants with infections unlikely to be resolved
within 2 weeks following registration should not be considered for the trial
• Participants must not have a known grade 2 or higher uncontrolled or untreated
hypercholesterolemia or hypertriglyceridemia
• Participants must not have any of the following:
• Cirrhosis at a level of Child-Pugh B (or worse),
• Cirrhosis (any degree) and a history of hepatic encephalopathy, or
• Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful
ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
• Participants must not be receiving any medications or substances that are inhibitors
or inducers of CYP3A. Treatment with strong CYP3A inhibitors or strong CYP3A inducers
within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to
initiation of study drug is prohibited.
• NOTE: Because the lists of these agents are constantly changing, it is important
to regularly consult a frequently updated medical reference. As part of the
enrollment/informed consent procedures, the participant will be counseled on the
risk of interactions with other agents, and what to do if new medications need to
be prescribed or if the participant is considering a new over-the-counter
medicine or herbal product. The participant wallet card should be presented to
the participant
• Participants must not have baseline fasting glucose (after 8-hour fast) > 160 mg/dL
(8.9 mmol/L) within 28 days prior to registration
• Participants with known diabetes mellitus must not require insulin therapy or have a
baseline fasting glucose >150 mg/dL (8.3 mmol/L) or high glycosylated hemoglobin
(Hb)A1c, (>= 8.0%), suggesting poorly controlled diabetes
• Participants who are on a stable dose of oral diabetes medication >= 2 weeks prior to
initiation of study drug treatment are eligible for enrollment
• Participants with a prior or concurrent malignancy whose natural history or treatment
(in the opinion of the treating physician) must not have a potential to interfere with
the safety or efficacy assessment of the investigational regimen
• Participants must not have lung disease requiring active systemic therapy or placing
participants at increased risk of toxicity related to study-directed therapy
including, but not limited to pneumonitis, interstitial lung disease, idiopathic
pulmonary fibrosis, cystic fibrosis, aspergillosis, active tuberculosis, or history of
opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
• Participants must not be pregnant or nursing. Individuals who are of reproductive
potential must have agreed to use an effective contraceptive method with details
provided as a part of the consent process. A person who has had menses at any time in
the preceding 12 consecutive months or who has semen likely to contain sperm is of
"reproductive potential". In addition to routine contraceptive methods, "effective
contraception" also includes surgery intended to prevent pregnancy (or with a
side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy,
bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the
semen
• Participants must not have psychiatric illness/social situations that would limit
compliance with study requirements
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
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
Show full eligibility criteria
Hide eligibility criteria
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.
*Note: Email is generally not a secure way to communicate sensitive or health-related information as there are many ways for unauthorized users to access email. You should avoid sending sensitive, detailed personal information by email.