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194 Study Matches

Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Based on PET Imaging

This phase III trial tests two questions by two separate comparisons of therapies. The first question is whether enhanced therapy (apalutamide in combination with abiraterone + prednisone) added to standard of care (prostate radiation therapy and short term androgen deprivation) is more effective compared to standard of care alone in patients with prostate cancer who experience biochemical recurrence (a rise in the blood level of prostate specific antigen [PSA] after surgical removal of the prostate cancer). A second question tests treatment in patients with biochemical recurrence who show prostate cancer spreading outside the pelvis (metastasis) by positron emission tomography (PET) imaging. In these patients, the benefit of adding metastasis-directed radiation to enhanced therapy (apalutamide in combination with abiraterone + prednisone) is tested. Diagnostic procedures, such as PET, may help doctors look for cancer that has spread to the pelvis. Androgens are hormones that may cause the growth of prostate cancer cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Metastasis-directed targeted radiation therapy uses high energy rays to kill tumor cells and shrink tumors that have spread. This trial may help doctors determine if using PET results to deliver more tailored treatment (i.e., adding apalutamide, with or without targeted radiation therapy, to standard of care treatment) works better than standard of care treatment alone in patients with biochemical recurrence of prostate cancer.
John Floberg, Assistant Professor
Male
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04423211
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Inclusion Criteria:

• STEP 0: REGISTRATION ELIGIBILITY CRITERIA
• Patient must be male and >= 18 years of age.
• Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma
• Patient must have biochemical recurrence (BCR) after RP, defined as follows:
• If time to BCR, defined as time to first detectable PSA ( > lower limit of normal for assay used) after RP, is < 12 months, a minimum PSA level of >= 0.2 ng/mL and a confirmatory reading of >= 0.2 ng/mL is required, per the American Urological Association (AUA) definition (Note: patients with a persistent PSA reading of at least 0.2 ng/mL are eligible)
• If time to BCR, defined as time to first detectable PSA (> lower limit of normal for assay used) after RP, is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is required
• If the patient has a detectable PSA (> lower limit of normal for assay used) at any time after RP AND has an eligible baseline SOC PET (PET1) with at least one positive lesion in any location, then there is no minimum PSA requirement
• Patients must have no definite evidence for extrapelvic metastatic disease by conventional imaging modalities (CIM) (CT abdomen/pelvis or MRI abdomen/pelvis AND bone scintigraphy, or equivalent), within 26 weeks prior to Step 0 registration. If a patient only has a study-eligible PET/CT or PET/MR (i.e., PET done without prior CIM): if the PET is negative for extrapelvic lesions, then baseline CIM is NOT required. If the PET positive for extrapelvic lesions, then patient should have a baseline CT/MRI for soft tissue lesions and/or a bone scan for osseous lesions
• Study eligible = PET using FDA-approved radiotracer and performed within 16 weeks prior to study registration
• Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT fields. Baseline PET/CT or PET/MR scan (PET1) is eligible for this study if the SOC PET scan is completed with an FDA approved radiotracer for prostate cancer after Step 0 registration and prior to Step 1 randomization OR up to 16 weeks prior to Step 0 registration
• Patient must be a candidate for SOC post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (ADT)
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient must not have started ADT for biochemical recurrence prior to baseline PET (PET1) imaging. A short course of low-dose anti-androgen such as bicalutamide, given after baseline study PET/CT but prior to study registration, is permitted as a brief temporizing measure in advance of starting protocol-approved SOC ADT.
• Patient must not be enrolled in another therapeutic clinical trial
• Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET scan and radiation treatment planning and delivery
• Patients undergoing a PET/MR must meet local institutional safety guidelines for MRI
• Patient must not have history of seizures or known condition that may cause predisposal to seizures (e.g., stroke or head trauma resulting in loss of consciousness) within 1 year prior to registration
• Patient must not have history of inflammatory bowel disease or any gastrointestinal disorder affecting absorption that is expected to increase risk of complication from radiotherapy
• Hemoglobin (Hgb) >= 9.0 g/dL (independent of transfusion and/or growth factors within 3 months prior to Step 0 registration) (obtained within 8 weeks prior to Step 0 registration)
• Leukocytes >= 3,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Absolute neutrophil count >= 1,500/mcL (obtained within 8 weeks prior to Step 0 registration)
• Platelets >= 100,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (patients with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, must have a direct bilirubin of < 1.5 x ULN to be eligible) (obtained within 8 weeks prior to Step 0 registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 8 weeks prior to Step 0 registration)
• Creatine < 1.5 x instituional ULN (or measured creatinine clearance > 30 mL/min)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class I or II (by patient symptoms) or A or B (by objective assessment)
• Patient must not have completed a course of prior pelvic radiation therapy for any reason
• Patient must agree not to father children while on study
• Patient must be English or Spanish speaking to be eligible for the QOL component of the study
• NOTE: Sites cannot translate the associated QOL forms
• STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
• Patient must have completed a baseline SOC PET/CT or PET/MR (PET1 scan) using FDA approved radiotracer with results of extra-pelvic metastases involvement known (positive or negative). The PET1 must have been completed after Step 0 registration and prior to Step 1 randomization OR up to 12 weeks prior to Step 0 registration
• For patients with negative extra-pelvic metastases, PET-imaging status of intra-pelvic nodes must be known (positive or negative)
• For patients with positive extra-pelvic metastases (defined as any PET positive lesions outside of standard salvage RT fields [prostate bed +/- typical whole pelvis]), the number of extra-pelvic lesions must be known (1
•5 or > 5 extra-pelvic lesions)
Biochemically Recurrent Prostate Carcinoma, Metastatic Prostate Carcinoma, Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8, Prostate
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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
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, 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
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SPEARHEAD-3 Pediatric Study

This is a pediatric basket study to investigate the safety and efficacy of afamitresgene autoleucel in HLA-A*02 eligible and MAGE-A4 positive subjects aged 2-21 years of age with advanced cancers
Christian Capitini, MD
All
2 Years to 21 Years old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05642455
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Inclusion Criteria:

• Age 2-21 years
• Body weight ≥ 10 kg
• Subject has histologically confirmed diagnosis of any one of the following cancers: (A) Synovial Sarcoma, (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma
• Must have previously received a systemic chemotherapy
• Measurable disease according to RECIST v1.1 (or INCR, 2017 Neuroblastoma only).
• HLA-A*02 positive
• Tumor shows MAGE-A4 expression confirmed by central laboratory.
• Performance Status: ECOG 0-1 or Lansky Score ≥ 80
Exclusion Criteria:

• HLA-A*02:05 in either allele; or any A*02 having same protein sequence as HLA-A*02:05
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide.
• History of autoimmune or immune mediated disease
• Known central nervous system (CNS) metastases.
• Other prior malignancy that is not considered by the Investigator to be in complete remission
• Clinically significant cardiovascular disease
• Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus
• Pregnant or breastfeeding
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus, Synovial Sarcoma, Malignant Peripheral Nerve Sheath Tumor (MPNST), Neuroblastoma, Osteosarcoma
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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.
Stage III Colon Cancer, Colon, Colon and Rectum
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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
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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
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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
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Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Breast Cancers

Patient will be treated with neratinib, an aromatase inhibitor and trastuzumab for 24 weeks prior to surgery, following an initial 3 weeks of neratinib alone, aromatase inhibitor alone or the combination of neratinib and an aromatase inhibitor. A breast biopsy will be performed prior to Day 1 of week 4 of treatment. Following surgery, patients will receive standard of care HER2-directed and endocrine therapy at the treating physician's discretion.
Kari Wisinski, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04886531
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Inclusion Criteria:
Subject must meet all of the following applicable inclusion criteria to participate in this study:
• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• Postmenopausal females. NOTE: Postmenopausal status defined as: prior bilateral oophorectomy, Age ≥ 60 years, or Age < 60 years and amenorrhea for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) or an estradiol level in postmenopausal ranges per local reference range.
• ECOG Performance Status of 0-2 within 28 days prior to registration.
• Anatomic, clinical stage I-III, invasive breast cancer, greater than 10mm
• HER2-positive (by the most recent ASCO-CAP criteria)
• ER positive (≥ 10%). NOTE: There is no requirement for PR status; PR positive or negative allowed.
• Resectable breast cancer in which pre-operative therapy is appropriate (T > 10mm and/or node-positive).
• Archival tissue from the diagnostic pre-treatment biopsy is required. This sample should be identified at screening and shipped by Week 4. If archival tissue is not available, the subject is not eligible for the study.
• Agreeable to repeat breast biopsy at 3 weeks after initiation of treatment.
• Candidate for either letrozole or anastrozole, as determined by the treating physician
• Left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) documented within 4 weeks prior to the study treatment.
• Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
• Hematological
• Platelet count ≥100,000/uL
• Absolute Neutrophil Count (ANC) ≥1500/uL
• Hemoglobin (Hgb) ≥10 g/dL
• Renal ---Calculated creatinine clearance: CrCl ≥60 mL/min using the Cockcroft-Gault formula
• Hepatic
• Bilirubin ≤1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 × ULN
• Alanine aminotransferase (ALT) ≤ 2.5 × ULN
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
• For patients with known serologic evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial.
• Ability of the subject to understand and comply with study procedures for the entire length of the study, as determined by the enrolling physician or protocol designee.
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
• Locally advanced or inflammatory breast cancer.
• Evidence of metastatic disease. Systemic imaging is not required.
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial: exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
• Active infection requiring systemic therapy.
• Requirement for use of a moderate or stonr CYP3A4 inhibitor or inducer during the study (see protocol).
• Treatment with any investigational drug within 14 days prior to registration or within 5 half-lives of the investigational product, whichever is longer.
• Subject has had major surgery within 14 days prior to registration or has not recovered from major side effects of the surgery (tumor biopsy is not considered as major surgery).
• Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) or significantly impair the ability to swallow capsules/tablets.
• Known history of myelodysplastic syndrome or acute myeloid leukemia.
• Subjects with any of the following conditions:
• History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 28 days prior to registration.
• Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to registration.
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to registration.
• Symptomatic congestive heart failure (New York Heart Association III-IV) or documented current cardiomyopathy with left ventricular ejection fraction (LVEF) <50%.
• Clinically significant cardiac ventricular arrhythmias (e.g. sustained ventricular tachycardia/ventricular fibrillation) or high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block) unless a pacemaker is in place.
• Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome.
• Any concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate subject participation in the clinical study or compromise compliance with the protocol.
Breast Cancer, HER2-positive Breast Cancer, ER Positive Breast Cancer, PR-Positive Breast Cancer, Breast
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Testing the Safety and Effectiveness of Radiation-based Treatment (Lutetium Lu 177 Dotatate) for Metastatic Prostate Cancer That Has Neuroendocrine Cells

This phase II trial studies how well lutetium Lu 177 dotatate works in treating patients with prostate cancer with neuroendocrine differentiation that has spread to other places in the body (metastatic). Neuroendocrine differentiation refers to cells that have traits of both hormone-producing endocrine cells and nerve cells. These cells release hormones into the blood in response to a signal from the nervous system. Hormones are biological substances that circulate through the bloodstream to control the activity of other organs or cells in the body. Lutetium Lu 177-dotate is a radioactive drug. It binds to a protein called somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu 177-dotatate builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog. Treatment with Lutetium Lu 177 dotatate may shrink the tumor in a way that can be measured in patients with metastatic prostate cancer with neuroendocrine differentiation.
John Floberg, Assistant Professor
Male
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05691465
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Inclusion Criteria:

• PRE-REGISTRATION ELIGIBILITY
• Patients must have metastatic prostate cancer with neuroendocrine differentiation, as determined by at least one of the following:
• Histologically confirmed small cell or neuroendocrine cancer from a primary prostate or metastatic biopsy. Neuroendocrine prostate cancer includes mixed small cell with adenocarcinoma histology, as well as small or large cells with positive neuroendocrine markers (e.g., chromogranin or synaptophysin)
• Prostate adenocarcinoma with molecular features of neuroendocrine differentiated cancer (e.g., 2 of the following 3: PTEN, TP53, or RB loss)
• Progression of visceral metastases in the absence of PSA progression
• Serum chromogranin A > 5x normal limit, or neuron-specific enolase > 2x normal
• Age >= 18 years. Prostate cancer is typically a disease of older men, with the average age at diagnosis being 65 years. Consequently, because the research topic is not relevant to children, no children will be included in this study. There is no upper limit to the age of participants eligible for this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 8 g/dL, prior to each dose of lutetium lu 177 dotatate
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
• Creatinine Cockcroft calculated creatinine clearance of >= 60 mL/min OR
• Glomerular filtration rate (GFR) of 60 mL/min/1.73 m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients should be New York Heart Association Functional Classification of class 2B or better
• Current disease progression according to PCWG3 criteria
• Ongoing use of luteinizing hormone-releasing hormone (LHRH) agonists/antagonists will be required (unless prior bilateral orchiectomy or pure neuroendocrine carcinoma histology) to maintain testosterone at castrate levels. Patients with a pure neuroendocrine carcinoma histology do not need to be undergoing LHRH agonist/antagonist therapy
• No concurrent use of other anti-cancer therapies
• Pregnancy Precaution: The effects of lutetium lu 177 dotatate on the developing human fetus are unknown. For this reason and because radionuclides are known to be teratogenic, male participants and their female partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her male partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of lutetium lu 177 dotatate administration. Patients must not donate sperm during the study and for 3 months after the last study drug administration
• Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible
• Patients will undergo a Gallium 68 Dotatate PET scan after enrollment. The Gallium 68 Dotatate PET must be positive to proceed with lutetium Lu 177 dotatate therapy. A positive scan will be defined as at least one lesion with an maximum standardized uptake value (SUVmax) > the average standardized uptake value (SUV) of normal liver. The positive lesion(s) can be in any location (bone metastases or visceral metastases). Patients with only bone metastases will be allowed
• REGISTRATION ELIGIBILITY: The gallium 68 dotatate PET is positive. A positive scan will be defined as at least one lesion with an maximum standardized uptake value (SUVmax) > the average SUV of normal liver. The positive lesion(s) can be in any location (bone metastases or visceral metastases). Patients with only bone metastases will be allowed.
• REGISTRATION ELIGIBILITY: Absolute neutrophil count ≥ 1,500/mcL
• REGISTRATION ELIGIBILITY: Platelets ≥ 100,000/mcL
• REGISTRATION ELIGIBILITY: Hemoglobin ≥ 8 g/dL, prior to each dose of lutetium Lu 177 dotatate
• REGISTRATION ELIGIBILITY: Total bilirubin ≤1.5 × institutional upper limit of normal (ULN)
• REGISTRATION ELIGIBILITY: AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
• REGISTRATION ELIGIBILITY: Creatinine Cockcroft calculated creatinine clearance of ≥ 60 mL/min OR
• REGISTRATION ELIGIBILITY: Glomerular filtration rate (GFR) of 60 mL/min/1.73 m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2
Exclusion Criteria:

• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Lutetium Lu 177 dotatate
• As per the Food and Drug Administration (FDA) package insert for Lutetium Lu 177 dotatate, use of long-acting somatostatin analogs (e.g., long-acting octreotide) is prohibited within 4 weeks prior to initiating Lutetium Lu 177 dotatate and during treatment. Use of short-acting somatostatin analogs is prohibited within 24 hours prior to initiating Lutetium Lu 177 dotatate and during treatment. Long-acting somatostatin analogs or short-acting somatostatin analogs will be allowed if the patient has a history of carcinoid syndrome and requires long-acting or short-acting somatostatin analogs for the control of his functional syndrome
• Patients with uncontrolled intercurrent illness
• Any of the following within 6 months before starting treatment: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV
• Uncontrolled hypertension as indicated by a systolic blood pressure >= 160 mmHg or diastolic blood pressure >= 100 mmHg at screening
Prostate, Metastatic Prostate Adenocarcinoma With Neuroendocrine Differentiation, Metastatic Prostate Neuroendocrine Carcinoma, Metastatic Prostate Small Cell Neuroendocrine Carcinoma, Stage IV Prostate Cancer AJCC v8
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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
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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
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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
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Inclusion Criteria:

• Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-S3 based on the presence of an actionable mutation as defined in EAY191
• GENERAL COMBOMATCH EAY191 REGISTRATION INCLUSION CRITERIA:
• Participants must be enrolled on the ComboMATCH Master Registration Trial EAY191
• Participants must have an activating AKT mutation (a known mutation in AKT1, AKT2, or AKT3, a single nucleotide variant, insertion, or deletion) as determined by the ComboMATCH screening assessment
• GENERAL COMBOMATCH EAY191 REGISTRATION EXCLUSION CRITERIA:
• Participants must not have an activating KRAS, NRAS, HRAS, or BRAF mutation (a single nucleotide variant, insertion, or deletion) as determined by the ComboMATCH screening assessment
• Participants must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191)
• Participants must have a histologically confirmed non-breast solid malignancy
• Participants must have locally advanced, unresectable, or metastatic disease in the opinion of the treating investigator
• Participants must have measurable disease documented by CT or MRI. Measurable disease must be assessed within 28 days prior to registration. Non-measurable disease must be assessed within 42 days prior to registration. The CT from a combined positron emission tomography (PET)/CT may be used only if it is of diagnostic quality. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1). Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration
• Participants with known brain metastases must have a CT/MRI scan to evaluate for central nervous system (CNS) disease and show no evidence of progression within 42 days prior to registration
• Participants must have completed any CNS-directed therapy and/or local therapy for spinal cord compression at least 28 days prior to registration
• Participants must not have spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days prior to registration, AND (2) participant has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to registration
• Participants must not have leptomeningeal disease
• Participants must have progressed within 6 months of taxane-based therapy in the neoadjuvant/adjuvant or metastatic setting
• Participants must not have received any prior AKT inhibitor (e.g., capivasertib or ipatasertib); prior PI3K/mTOR inhibitor is acceptable
• Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic, radiation, or hormonal therapy for cancer treatment while receiving treatment on this study
• Participants must be >= 18 years of age
• Participants must be able to swallow oral medications whole
• Participants must have a pre-study history and physical exam done within 28 days prior to registration
• Participants must have a Zubrod performance status of 0-2 within 28 days prior to registration
• Participants must have adverse events resolved =< grade 1 related to any prior therapy, except alopecia within 14 days prior to registration
• Participants with neuropathy must have resolved to < grade 2 within 14 days prior to registration
• Leukocytes >= 3 x 10^3/uL (within 28 days prior to registration)
• Absolute neutrophil count >= 1.5 x 10^3/uL (within 28 days prior to registration)
• Platelets >= 100 x 10^3/uL (within 28 days prior to registration)
• Total bilirubin =< institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN (within 28 days prior to registration)
• Aspartate aminotransferase (AST) & alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to registration)
• Participants must have adequate cardiac function, class IIB (2B) or better. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification
• Participants must have a measured OR calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn within 28 days prior to registration
• Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test on the most recent test results obtained within 6 months prior to registration
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to registration
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration
• Participants must have an electrocardiography (ECG) performed (if clinically indicated with a corrected QTc interval of =< 470 msec) within 28 days prior to registration
• Participants must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ipatasertib and/or paclitaxel
• Participants must not have an active small/large bowel inflammation such as ulcerative colitis or Crohn's disease
• Participants must not have grade 2 or higher uncontrolled intercurrent illness
• NOTE: To receive an agent, participant must not have any uncontrolled intercurrent illness requiring antibiotic/antiviral/antifungal therapy or interventional procedures. Participants with infections unlikely to be resolved within 2 weeks following registration should not be considered for the trial
• Participants must not have a known grade 2 or higher uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
• Participants must not have any of the following:
• Cirrhosis at a level of Child-Pugh B (or worse),
• Cirrhosis (any degree) and a history of hepatic encephalopathy, or
• Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
• Participants must not be receiving any medications or substances that are inhibitors or inducers of CYP3A. Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug is prohibited.
• NOTE: Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product. The participant wallet card should be presented to the participant
• Participants must not have baseline fasting glucose (after 8-hour fast) > 160 mg/dL (8.9 mmol/L) within 28 days prior to registration
• Participants with known diabetes mellitus must not require insulin therapy or have a baseline fasting glucose >150 mg/dL (8.3 mmol/L) or high glycosylated hemoglobin (Hb)A1c, (>= 8.0%), suggesting poorly controlled diabetes
• Participants who are on a stable dose of oral diabetes medication >= 2 weeks prior to initiation of study drug treatment are eligible for enrollment
• Participants with a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) must not have a potential to interfere with the safety or efficacy assessment of the investigational regimen
• Participants must not have lung disease requiring active systemic therapy or placing participants at increased risk of toxicity related to study-directed therapy including, but not limited to pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
• Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is of "reproductive potential". In addition to routine contraceptive methods, "effective contraception" also includes surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
• Participants must not have psychiatric illness/social situations that would limit compliance with study requirements
Locally Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Malignant Solid Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
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Study Transplanting Bone Marrow Cells Into Salivary Glands to Treat Dry Mouth Caused by Radiation Therapy

The goal of this clinical research study is to evaluate the safety and tolerability of injecting certain cells that you produce in your bone marrow called mesenchymal stem cells (MSCs) into your salivary glands. Participants will have head and neck cancer that was treated with radiation therapy, and in this study will: - Undergo a collection of bone marrow using a needle; - Donate saliva; - Undergo a salivary gland ultrasound; and, - Complete questionnaires that ask about dry mouth Participants can expect to be in this study for up to 30 months.
Randall Kimple, MD, PhD
All
18 Years to 90 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT05820711
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Inclusion Criteria:

• History of histological diagnosis of head and neck cancer (HNC) that was treated with radiation therapy and currently clinically or radiologically no evidence of disease (NED)
• Xerostomia, defined as patient reported salivary function (pre-treatment) ≤ 80% of healthy (pre-radiation)
• ≥ 18 years of age, ≤ 90 years of age.
• Patients ≥ 2 years from completion of radiation therapy for HNC
• Karnofsky performance status ≥ 70, patient eligible for bone marrow aspirate with wakeful anesthesia
• Willing and able to give informed consent
• Radiographically confirmed submandibular gland(s)
Exclusion Criteria:

• Salivary gland disease (i.e., sialolithiasis)
Head and Neck Cancer, Xerostomia, Lip, Oral Cavity and Pharynx, Larynx, Head and Neck
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Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder

This study is open to adults with advanced cancer in the biliary tract, pancreas, lung, or bladder. This is a study for people for whom previous treatment was not successful or no treatment exists. The purpose of this study is to find out whether a medicine called BI 907828 helps people with cancer in the biliary tract, pancreas, lung, or bladder. BI 907828 is a so-called MDM2 inhibitor that is being developed to treat cancer. All participants take BI 907828 as a tablet once every 3 weeks. Participants may continue to take BI 907828 as long as they benefit from treatment and can tolerate it. They visit the study site regularly. At the study site, doctors regularly check the size of the tumour and whether it has spread to other parts of the body. The doctors also regularly check participants' health and take note of any unwanted effects.
Jeremy Kratz, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05512377
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Inclusion Criteria:

• Diagnosis of a solid tumour which meets the criteria for an open trial cohort:
• Cohorts 1 and 1-CN (biliary tract adenocarcinoma): Locally advanced or metastatic biliary tract adenocarcinoma (intra- and extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary cancer).Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards; or (in the opinion of the investigator) patients are unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.
• Cohort 2 (pancreatic ductal adenocarcinoma): Locally advanced or metastatic pancreatic ductal adenocarcinoma. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
• Cohort 3 (lung adenocarcinoma): Locally advanced or metastatic lung adenocarcinoma. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
• Cohort 4 (urothelial bladder cancer): Locally advanced or metastatic urothelial bladder cancer. Patients must have unresectable disease and have received all available conventional therapies known to confer clinical benefit for their disease based on local approved standards.
• Written pathology report / molecular profiling report indicating Mouse double minute 2 homolog (MDM2) amplification or a copy number ≥8 and tumor protein 53 (TP53) wild-type status. This must have been confirmed with a tissue-based test. A test with liquid biopsy is not accepted.
• Archival tissue (formalin fixed paraffin embedded [FFPE] tumour blocks or slides) must be provided for retrospective confirmation of MDM2 amplification and TP53 status.
• Presence of at least 1 measurable target lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Patient must be willing to donate mandatory blood samples for the pharmacokinetics, pharmacodynamics, and biomarker analyses
• Adequate organ function
• All toxicities related to previous anti-cancer therapies have resolved to ≤Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 prior to trial treatment administration (except for alopecia and amenorrhea / menstrual disorders which can be of any grade and peripheral neuropathy which must be ≤CTCAE Grade 2).
• Life expectancy ≥3 months at the start of treatment in the opinion of the investigator.
• Provision of signed and dated, written informed consent form (ICF) in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
• Male or female patients ≥18 years old at the time of signature of the ICF. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use 2 medically acceptable methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at screening, during trial participation, and until 6 months and 12 days after last dose for women and 102 days after last dose for men. A list of contraception methods meeting these criteria is provided in the patient information.
Exclusion Criteria:

• Previous administration of brigimadlin (BI 907828) or any other MDM2-p53 or mouse double minute 4 (MDMX, MDM4)-p53 antagonist.
• Active bleeding, significant risk of haemorrhage (e.g. previous severe gastrointestinal bleeding, previous haemorrhagic stroke at any time), or current bleeding disorder (e.g. haemophilia, von Willebrand disease).
• Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to start of trial treatment or planned within 6 months after screening (e.g. hip replacement).
• Clinically significant previous or concomitant malignancies in the opinion of the investigator affecting the efficacy and/or outcome of the trial.
• Patients who must or intend to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
• Currently enrolled in another investigational device or drug trial.
• Any history of, or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the trial drug.
• Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator's opinion, makes the patient an unreliable trial participant). Further exclusion criteria apply.
Pancreatic Neoplasms, Solid Tumors, Biliary Tract Cancer, Lung Neoplasms, Bladder Cancer, Liver, Lung, Prostate, Urinary Bladder, Bladder
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Liposomal Irinotecan With TAS102 and Bevacizumab for Patients With Metastatic Colorectal Cancer

This study is being done to see if combining liposomal irinotecan with TAS102 and bevacizumab confers clinical benefit for patients with treatment refractory metastatic colorectal cancer.
Dustin Deming, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05854498
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Inclusion Criteria:

• Patients must be ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance must be 0 or 1.
• Patients must have a histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma and be metastatic or unresectable.
• The cancer must be mismatch repair proficient.
• Patients must have had prior treatment with 5-fluorouracil, oxaliplatin, irinotecan containing regimens. If RAS wild-type must have received prior anti-EGFR therapy with either cetuximab or panitumumab. If RAS wild-type and HER2 positive then must have had a prior HER2 targeted therapy.
Exclusion Criteria:

• Uncontrolled concurrent medical illness that would not allow for the completion of the planned therapy.
• Patients whose cancers possess BRAF V600 mutations are excluded.
• Patients must stop the use of strong inducers/inhibitors of CYP3A4 at least 2 weeks before initiating therapy.
• Patients must not have mismatch repair deficient or microsatellite instability high cancers.
• Patients must not have received prior TAS102.
Colon, Colon and Rectum, Metastatic Colorectal Cancer
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Specialty Compared to Oncology Delivered Palliative Care for Patients With Acute Myeloid Leukemia (SCOPE-L)

This research study is evaluating whether primary palliative care is an alternative strategy to specialty palliative care for improving quality of life, symptoms, mood, coping, and end of life outcomes in patients with acute myeloid leukemia (AML).
Priyanka Pophali
All
18 Years to 120 Years old
N/A
This study is also accepting healthy volunteers
NCT05237258
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Inclusion Criteria:

• Patient Inclusion Criteria
• Hospitalized patients (age ≥ 18 years) with high-risk AML defined as:
• Patients with new diagnosis ≥ 60 years of age
• An antecedent hematologic disorder
• Therapy related-disease
• Relapsed or primary refractory AML
• Receiving treatment with either a) intensive chemotherapy (7+3) or modification of this regimen on a clinical trial, or a similar intensive regimen requiring prolonged hospitalization; or b) hypomethylating agents +/- additional agents or modification of this regimen on a clinical trial
• Caregiver Inclusion Criteria
• Adult (≥18 years) relative or friend of a participating patient who the patient identifies as living with or has in-person contact with them at least twice per week.
Exclusion Criteria:

• Patient Exclusion Criteria
• Patients with a diagnosis of acute promyelocytic leukemia (APML)
• Patients with AML receiving supportive care alone
• Patients with psychiatric or cognitive conditions which the treating clinicians believe prohibits informed consent or compliance with study procedures
• Patients seen by a palliative care clinician [MD or APP] during two previous hospitalizations in the six months prior to enrollment
Myeloid and Monocytic Leukemia, Leukemia, Relapsed Adult AML, Primary Refractory Acute Myeloid Leukemia, High Risk Acute Myeloid Leukemia
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(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors

This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination with sunitinib. This is a multi-part study that will enroll approximately 426 patients. Part 1 consists of two evaluations: 1) confirming the dose of an updated formulation of CGT9486 to be used in subsequent parts in approximately 20 patients who have received at least one prior line of therapy for GIST and 2) evaluating for drug-drug interactions between CGT9486 and sunitinib in approximately 18 patients who have received at least two prior tyrosine kinase inhibitors (TKIs) for GISTs. The second part of the study will enroll approximately 388 patients who are intolerant to, or who failed prior treatment with imatinib only and will compare the efficacy of CGT9486 plus sunitinib to sunitinib alone with patients being randomized in a 1:1 manner.
Sam Lubner, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05208047
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Key
Inclusion Criteria:
1. Histologically confirmed locally advanced, metastatic, and/or unresectable GIST. Molecular pathology report must be available for Part 2; if molecular pathology report is unavailable or inadequate, an archival or fresh tumor tissue sample will be required to evaluate mutational status prior to randomization. 2. Documented disease progression on or intolerance to imatinib 3. Subjects must have received the following treatment:
• Part 1a: Treatment with ≥1 prior lines of therapy for GIST
• Part 1b: Treatment with ≥2 prior TKI for GISTs
• Part 2: Prior treatment with imatinib only 4. Have at least 1 measurable lesion according to mRECIST v1.1 5. ECOG
•0 to 2 6. Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits Key
Exclusion Criteria:
1. Known PDGFR driving mutations or known succinate dehydrogenase deficiency 2. Clinically significant cardiac disease 3. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug 4. Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption 5. Any active bleeding excluding hemorrhoidal or gum bleeding 6. Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody. 7. Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening 8. Received strong CYP3A4 inhibitors or inducers 9. Received sunitinib within 3 weeks (Part 1a, Part 1b)
Advanced Gastrointestinal Stromal Tumors, Metastatic Cancer, Soft Tissue, Sarcoma
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Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults

This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.
Ryan Mattison, MD
All
18 Years to 75 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04530565
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Inclusion Criteria:

• ELIGIBILITY CRITERIA FOR PREREGISTRATION (TO STEP 0)
• Patient must be >= 18 and =< 75 years of age
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-3
• Patient must be newly diagnosed with B-ALL or is suspected to have ALL
• Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the presence of BCR-ABL translocation must be confirmed centrally. Patients can be registered and begin Step 1 therapy while awaiting central laboratory eligibility confirmation
• NOTE: Bone marrow aspirate and/or peripheral blood specimen must be submitted to the American College of Radiology Imaging Network (ECOG-ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patient's eligibility for registration to Step 1 or confirm patient evaluability. Centrally fluorescence-activated cell sorting (FACS) analysis will be performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of receipt of the specimen to the submitting institution. Bone marrow aspirate is to be from first pull (initial or re-direct). Specimens must contain sufficient blast cells. In cases where the bone marrow aspiration may be inadequate, or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood may be submitted, given that adequate circulating blasts are present (> 10%). If a diagnosis of BCR-ABL positive B-ALL has already been established by local Clinical Laboratory Improvement Act (CLIA) certified laboratories, the patient may be registered to Step 1 without waiting for central confirmation
• Patient must not have a diagnosis of BCR/ABL T-ALL
• Patient must not have received chemotherapy for B-ALL. Patients who received up to five days of hydroxyurea or steroids of any kind with the aim to reduce disease burden prior to study registration to Step 1 are eligible
• Patients who started any kind of TKI prior to study registration to Step 1 are allowed to proceed on the study if they received no more than 14 days of TKI
• Patient must not have unstable epilepsy that requires treatment
• Patients with lymphoid blast crisis CML are not eligible
• ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1
• Patient must have a diagnosis of Philadelphia chromosome positive (Ph+) ALL that has been determined locally and bone marrow and/or peripheral blood was sent and receipt confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center
• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient 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)
• Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of step 1 registration, while on study treatment, and until at least six months after the last dose of study treatment
• Total bilirubin =< 3 mg/dL (patients with Gilbert's syndrome must have a total bilirubin =< 5 mg/dL) (obtained =< 28 days prior to step 1 registration)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X the institutional upper limit of normal (ULN) (obtained =< 28 days prior to step 1 registration)
• Estimated creatinine clearance > 45 mL/min (based on Cockcroft-Gault equation) (obtained =< 28 days prior to step 1 registration)
• Patients with acute organ dysfunction at step 1 registration, which may be attributed to leukemia can be registered regardless of lab results at presentation. Such patients will be allowed to register and can start Arm A steroid + TKI therapy but will only be allowed to proceed to Step 2 randomization if the eligibility criteria outlined is met
• Patients who presented with no evidence of acute organ dysfunction but during Step 0 experienced a rise in liver enzymes which investigator suspects to be a side effect of any of prescribed drugs, are allowed to be registered regardless of the level of liver enzymes. Step 2 Randomization must be withheld until the eligibility criteria outline is met but no more than 14 days after concluding Arm A therapy
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and if indicated, on treatment
• Patients with a prior 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
• Patient must not have active concomitant malignancy. Patients on chronic hormonal therapy for breast or prostate cancer or patients treated with maintenance with targeted agents but are in remission with no evidence for the primary malignancies are eligible
• 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 must be class 2B or better. An ECHO/MUGA is required.
• Investigators must confirm which TKI patient is to receive
• NOTE: Patients with known T315I mutation status should receive ponatinib treatment
• NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during Step 1. The investigator must re-specify dasatinib or ponatinib prior to Step 2 randomization and from then on patients must receive the pre-selected TKI only
• ELIGIBILITY CRITERIA FOR RANDOMIZATION TO STEP 2
• Patient must have completed at least 7 and no more than 21 days of protocol-treatment on Arm A prior to step 2 randomization. (Days in which arm A therapy was withheld for any reason are not counted)
• NOTE: First day of steroids prescription after registration will be considered as the first day of study therapy. The selected TKI must be initiated prior to randomization
• Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =< 2 X institutional upper limit of normal (ULN)
• AST(SGOT)/ ALT(SGPT) =< 2 X the institutional upper limit of normal (ULN)
• Estimated creatinine clearance > 45 mLg/min (based on Cockcroft-Gault equation)
• Investigators must confirm which TKI patient is to receive.
• NOTE: Patients with known T315I mutation status should receive ponatinib treatment
• For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization
• Patient must not have active central nervous system (CNS) involvement by leukemic blasts. Patients with signs of CNS involvement at presentation are eligible for randomization if clearance of blasts from the cerebrospinal fluid (CSF) is demonstrated
• Patients must have resolved any serious infectious complications related to therapy
• Any significant medical complications related to therapy must have resolved
• ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 3 (RE-INDUCTION)
• Institution has received centralized MRD results confirming positive status
• Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =< 2 X institutional ULN
• Patients who presented with acute organ dysfunction must have AST (SGOT)/ALT (SGPT) =< 2 X institutional upper limit of normal (ULN)
• Patients who presented with acute organ dysfunction must have an estimated creatinine clearance > 45 mL/min (based on Cockcroft-Gault equation)
• Investigators must confirm which TKI patient is to receive
• NOTE: Patients with known T315I mutation status should receive ponatinib treatment
• For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined
• Step 3 (Re-Induction): Patients must have resolved any serious infectious complications related to therapy
• Step 3 (Re-Induction): Any significant medical complications related to therapy must have resolved
Exclusion Criteria:

• Patient must not have complaints of symptoms and/or have clinical and/or radiological signs that indicate an uncontrolled infection or any other concurrent medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol
B Acute Lymphoblastic Leukemia With t(9,22)(q34.1,q11.2), BCR-ABL1, Lymphoid Leukemia, Leukemia
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Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study

This phase III trial compares early treatment with venetoclax and obinutuzumab versus delayed treatment with venetoclax and obinutuzumab in patients with newly diagnosed high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with the venetoclax and obinutuzumab early (before patients have symptoms) may have better outcomes for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma compared to starting treatment with the venetoclax and obinutuzumab after patients show symptoms.
Priyanka Pophali
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04269902
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Inclusion Criteria:

• Participants must have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (collectively referred to as CLL throughout) according to the 2018 International Workshop on CLL. Participants must have been diagnosed within 18 months prior to registration
• Participants must have CLL-International Prognostic Index (CLL-IPI) score >= 4 and/or complex cytogenetics (defined as 3+ chromosomal abnormalities)
• Cytogenetic AND/OR FISH analyses must be completed at a Clinical Laboratory Improvement Act (CLIA)-approved (or laboratories accredited under Accreditation Canada Diagnostics to conduct FISH analyses) laboratory within 18 months prior to registration. At minimum, FISH panel should use probes to detect for abnormalities in chromosomes 13q, 12, 11q, and 17p
• TP53 gene mutation analysis performed at any CLIA-approved (or laboratories accredited under Accreditation Canada Diagnostics) lab (if completed) must be obtained within 18 months prior to registration. This sequencing test is distinct from FISH studies for del(17p)
• Note: TP53 gene mutation analysis is recommended but not required if the participant meets disease-related study criteria via a combination of risk factors that totals a score of 4 on the CLL-IPI score and/or has complex cytogenetics completed
• Immunoglobulin heavy chain locus variable (IgVH) gene mutation analysis performed at any CLIA-approved lab (or laboratories accredited under Accreditation Canada Diagnostics) must be obtained prior to registration (at any time prior to registration)
• Serum beta-2 microglobulin level must be obtained within 28 days prior to registration
• Participants must not meet any of the IWCLL specified criteria for active CLL therapy
• Treatment with high dose corticosteroids and/or intravenous immunoglobulin for autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment
• Steroids used for treatment of conditions other than CLL/SLL must be at a dose of at most 20 mg/day of prednisone or equivalent corticosteroid at the time of registration
• Prior therapy with anti CD20 monoclonal antibodies is not allowed
• Participants must not have received or be currently receiving any prior CLL-directed therapy, including non-protocol-related therapy, anti-cancer immunotherapy, experimental therapy (with exception of agents approved for emergency access use for the prevention or treatment of COVID-19), or radiotherapy
• Participants must not be receiving or planning to receive any other investigational agents before completing protocol therapy
• Participants must be >= 18 years of age
• Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Platelet count >= 100,000/mm^3 within 28 days prior to registration
• Absolute neutrophil count (ANC) >= 1,000/mm^3 within 28 days prior to registration
• Creatinine clearance >= 30mL/min (by Cockcroft Gault) within 28 days prior to registration
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN) within 28 days prior to registration
• Total bilirubin =< 2.0 x ULN (or 5.0 x ULN if the participant has a history of Gilbert's disease), within 28 days prior to registration
• Participants must be able to take oral medications
• Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Participants with history of malignancy are allowed providing the cancer has not required active treatment within 2 years prior to registration (hormonal therapy is permissible). The following exceptions are permissible: basal cell, squamous cell skin, or non-melanomatous skin cancer, in situ cervical cancer, superficial bladder cancer not treated with intravesical chemotherapy or Bacillus Calmette-Guerin (BCG) within 6 months, localized prostate cancer requiring no more than chronic hormonal therapy, or localized breast cancer requiring no more than chronic hormonal therapy
• Participants must not have current, clinically significant gastrointestinal malabsorption, in the opinion of treating doctor
• Participants must not have cirrhosis
• Obinutuzumab has been associated with hepatitis reactivation. Participants must not have uncontrolled active infection with hepatitis B or C. Participants with latent hepatitis B infection must agree to take prophylaxis during and for 6 months following active protocol therapy with V-O.
• Active infection with hepatitis B or C:
• Active infection is defined as detectable hepatitis B deoxyribonucleic acid (DNA) or hepatitis C ribonucleic acid (RNA) by quantitative polymerase chain reaction (PCR).
• Latent infection with hepatitis B:
• Latent infection is defined as meeting all of the following criteria:
• Hepatitis B surface antigen positive
• Anti-hepatitis B total core antibody positive
• Anti-hepatitis IgM core antibody undetectable
• Hepatitis B PCR undetectable
• Participants with latent hepatitis B infection must agree to take prophylaxis with anti-hepatitis agents during and for 6 months following active protocol therapy with V-O.
• Participants who have received intravenous immunoglobulin (IVIG) therapy within 6 months who are hepatitis B core total antibody positive but PCR undetectable are not mandated to take prophylaxis
• Participants must not have had major surgery within 30 days prior registration or minor surgery within 7 days prior to registration. Examples of major surgery include neurosurgical procedures, joint replacements, and surgeries that occur inside the thoracic or abdomino-pelvic cavities. Examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint. If a participant has had a bone marrow biopsy for diagnosis or evaluation of CLL, this will not exclude the participant from registration to the study. If there is a question about whether a surgery is major or minor, this should be discussed with the Study Chair
• Participants must not have known bleeding disorders (e.g., von Willebrand's disease or hemophilia)
• Participants must not have a history of stroke or intracranial hemorrhage within 6 months prior to enrollment
• Participants must not require continued therapy with a strong inhibitor or inducer of CYP3A4/5, as venetoclax is extensively metabolized by CYP3A4/5
• Participants must not have uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura
• Participants must not have any currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification
• Participants must not have a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment
• Participants must not be pregnant or nursing, as there are no safety data available for these drug regimens during pregnancy. Women/men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
• Participants must agree to have specimens submitted for translational medicine (MRD) as outlined
• Participants must be offered the opportunity to participate in specimen banking for future research as outlined.
• NOTE: With participant's consent, the site must follow through with specimen submission as outlined
• Participants who are able to complete patient reported outcome (PRO) forms in English, Spanish, French, German, Russian or Mandarin must agree to participate in the quality of life assessments. (Those participants who are unable to read and write in English, Spanish, French, German, Russian or Mandarin may be registered to S1925 without contributing to the quality of life portion of the study.)
• Participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Lymphoid Leukemia, Leukemia
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Pilot Study of Imatinib Cetuximab Combo for H & N Cancer

The goal of this clinical trial is to find if levels of a protein called AXL in tumor cells relate to how tumors respond to cetuximab (CTX) combined with imatinib in participants with head and neck cancer. This interventional study will occur in the time between diagnosis of your cancer and surgery to remove your tumor or radiation or chemoradiation treatment of your primary cancer. Participants will undergo a research blood draw and a research biopsy as part of the screening process, and will be in this research study for approximately 13 to 16 months.
Justine Bruce, MD
All
18 Years and over
Early Phase 1
This study is NOT accepting healthy volunteers
NCT05816785
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Inclusion Criteria:

• Age > 18 years at the time of consent.
• Histological confirmation of squamous cell carcinoma of the head and neck.
• For those patients with oropharyngeal cancer, subjects must have either
• HPV-negative status by p16 expression or HPV-DNA Expression.
• HPV-positive status by p16 expression AND a >10 pack year smoking history.
• Subjects must be appropriate candidates for definitive curative intent treatment, either via surgical resection, definitive radiation therapy alone, or definitive concurrent chemoradiation therapy.
• For the screening research biopsy, subjects must have sufficient tumor volume (approximately 10 cc) to accommodate at minimum 2-3 core samples for the research biopsy.
• For the post-treatment (CTX/Imatinib) research biopsy, subjects who are scheduled to receive definitive radiation therapy (+/- concurrent chemotherapy) are required to have sufficient tumor volume to accommodate at minimum 2-3 core samples for the research biopsy.
• Demonstrate adequate organ function; all screening labs to be obtained within 28 days prior to registration.
Exclusion Criteria:

• Subjects with a diagnosis of nasopharyngeal carcinoma, advanced cutaneous squamous cell carcinoma of the head and neck, or salivary gland tumors are excluded from this study.
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.
• Prior chemotherapy, radiotherapy, or major surgery within 8 weeks of study enrollment or those who have not recovered (to grade ≤ 1 or baseline) from clinically significant adverse events due to agents administered more than 8 weeks earlier (alopecia and fatigue excluded). Clinical significance to be determined by the study investigator.
• Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
• Subjects who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to imatinib or CTX.
Head and Neck Cancer, Squamous Cell Carcinoma of Head and Neck, Lip, Oral Cavity and Pharynx, Esophagus, Head and Neck
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Study of Cabozantinib and Nivolumab in Metastatic Castration Resistant Prostate Cancer (CANOPY)

This is a multicenter, single-arm, two-stage open-label phase 2 study of the combination of cabozantinib + nivolumab in subjects with advanced castration-resistant prostate cancer (CRPC).
Christos Kyriakopoulos, MD
Male
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05502315
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Inclusion Criteria:
Subjects must meet all of the following applicable inclusion criteria to participate in this study:
• Willing and able to provide, or have a legally authorized representative provide, written informed consent and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
• Males 18 years of age and above.
• Histological or cytological proof of prostate adenocarcinoma.
• ECOG status of ≤ 2
• Progressive mCRPC as defined: 1) castrate levels of serum testosterone < 50 ng/dL AND 2) progressive disease as defined by PSA or radiographic progression. Subjects with measurable and non-measurable disease (i.e., bone only metastases) are allowed. NOTE: ENROLLMENT of subjects with non-measurable disease (i.e., bone only metastases) will be capped at 50% of enrollment target (n=25).
• Must have exposure to one prior taxane (or be taxane ineligible or refuse taxane) AND one prior AR-targeting agent (for example, abiraterone, enzalutamide, apalutamide, darolutamide). Receipt of taxane or AR-targeting agent may be in the hormone sensitive or castration resistant setting.
• Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Normal organ function with acceptable initial laboratory values within 14 days of treatment start:
• WBC: ≥ 2,500/mcL
• ANC: ≥ 1,500/mcL
• Hemoglobin: ≥ 9 g/dL (transfusions are permitted)
• Platelet count: ≥ 100,000/mcL
• Serum creatinine or calculated Creatinine Clearance: Serum creatinine ≤ 1.5 x ULN or calculated CrCl ≥ 30 mL/min as defined by Cockcroft-Gault equation
• Total Bilirubin: ≤ 1.5 x ULN (≤ 3 x ULN for subjects with documented Gilbert's disease)
• SGOT (AST): ≤ 3 x ULN
• SGPT (ALT): ≤ 3 x ULN
• Alkaline Phosphatase (ALP): ≤ 5 x ULN with documented bone metastases
• Serum Albumin: ≥ 2.8 g/dL
• Urine protein/creatinine ratio (UPCR): ≤ 2 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 2 g
• Subjects must agree to use a medically acceptable method of birth control as outlined in the protocol
• HIV-positive with negative viral loads on stable antiretroviral regimen will be considered eligible. Subjects must have CD4 count > 350.
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
• Small cell or neuroendocrine component or histology.
• Prior cabozantinib or checkpoint inhibitor.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or investigational systemic anti-cancer agent within 4 weeks before first dose of study treatment.
• Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment initiation. Treatment with investigational prostate cancer directed therapy within 4 weeks of treatment initiation. Treatment with enzalutamide within 4 weeks of treatment initiation.
• Receipt of more than 1 line of chemotherapy (including both hormone sensitive and CRPC). First-generation anti-androgen use (such as bicalutamide) will not be tabulated as a line of therapy.
• Administration of a live, attenuated vaccine within 30 days prior to first dose of study treatment.
• Active autoimmune disease or condition requiring prednisone >10 mg daily (or equivalent). Physiologic replacement is permitted. Topical, ocular, intra-articular steroids or inhaled corticosteroids are permitted.
• Imminent or established spinal cord compression based on clinical and/or imaging findings.
• Radiation therapy within 1 week of study treatment start.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment.
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Malabsorption syndrome.
• Requirement for hemodialysis or peritoneal dialysis.
• History of solid organ or allogenic stem cell transplant.
• Active hepatitis B/C or positive TB test with active mycobacterial infection requiring systemic treatment.
• Active treatment (within 5 days of registration) with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.
• Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion above) for at least 1 week before first dose of study treatment.
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation
• The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
• Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
• Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.
• Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
• Lesions invading or encasing any major blood vessels.
• Other clinically significant disorders that would preclude safe study participation.
• Serious non-healing wound/ulcer/bone fracture.
• Uncompensated/symptomatic hypothyroidism.
• Moderate to severe hepatic impairment (Child-Pugh B or C).
• Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
• Corrected QT interval calculated by Fridericia formula (QTcF) >500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment [add reference for Fridericia formula]. NOTE: If a single ECG shows a QTcF with an absolute >500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
• Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer or superficial bladder cancer.
• Known allergy to any of the compounds under investigation.
• Inability to swallow tablets.
Prostate, Castration-resistant Prostate Cancer, Metastatic Cancer
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TRAQinform Assessment of Immunotherapy Response (AIQ TRAQinform)

The intent of this study is to evaluate the actionable information output from the TRAQinform Immuno technology in a prospective, non-interventional clinical study. Subjects with metastatic melanoma treated with standard of care (SOC) dual-agent immunotherapy will be enrolled. Subjects will receive SOC immunotherapy monitored for treatment response with FDG PET/CT's at baseline (SOC), after 3-4 weeks of treatment (non-SOC) and 12 at weeks of treatment (SOC).
Vincent Ma, MD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT05819255
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Inclusion Criteria:

• Diagnosis of metastatic melanoma and is planned to start or has received one cycle of treatment with standard of care, dual-agent immunotherapy.
• Previous adjuvant anti-PD-I monotherapy is allowed. Patients must be greater than 6 months from the last treatment.
• Previous adjuvant BRAF/MEK therapy is allowed.
• Ability to tolerate 3 FDG PET/CT procedures. One at baseline, prior to the start of the combination immuno therapy, after 3
•4 weeks of the combination immunotherapy treatment, and at 12 weeks of the combination treatment.
• Estimated life expectancy of greater than 12 months at screening.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening.
• Deemed suitable for starting standard of care combination immunotherapy for metastatic melanoma.
• Willing and able to provide informed consent for FDG PET/CT imaging.
Exclusion Criteria:

• Any concurrent disease, infection, or comorbid condition that interferes with the ability of the patient to participate in the trial; places the patient at undue risk; or complicates the interpretation of the data, in the opinion of the investigator.
• A second malignancy
• Pregnancy or women who are breast feeding
Melanoma, Skin, Melanoma/Skin cancer, Melanoma
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Study to Evaluate the Safety and Efficacy of Oral NRC-2694-A in Combination With Paclitaxel in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma, Who Progressed on or After Immune Checkpoint Inhibitor Therapy

This is a Phase 2, open-label, multicenter, single-arm study of NRC-2694-A in combination with paclitaxel in patients with R/M HNSCC with progression on or after ICI therapy. A total of approximately 46 male and female patients will be enrolled. This sample size is based on Simon's 2-stage design with historical control ORR of 30% and a target ORR of 50%.
Justine Bruce, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05283226
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Inclusion Criteria:

• Is willing and capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
• Is male or female aged 18 years or older at the time of consent.
• Has histologically confirmed unresectable R/M HNSCC (oral cavity, oropharynx, hypopharynx, and larynx).
• Has documented radiographical progressive disease assessed by the principal investigator per RECIST v1.1.
• Has a measurable lesion per RECIST v1.1.
• Has ECOG performance status score of ≤2.
• Must have progressed during or after receiving ICI therapy, such as pembrolizumab or nivolumab. Patients with prior immune-mediated reactions due to ICI therapies (eg, pembrolizumab or nivolumab) and who had recovered prior to study entry will also be eligible.
• Female patients of childbearing potential should have a negative urine test before enrollment. If the urine pregnancy test is positive or gives equivocal results, a serum pregnancy will be required for confirmation.
• Patients of reproductive age must use acceptable methods of contraception throughout the study period and for 30 days following the last dose of investigational product (see protocol for further guidance).
• During screening and at subsequent visits, the investigator should ensure adequate bone marrow reserve (neutrophil count ≥1500/mm3, platelet count ≥100,000/mm3, and hemoglobin level 8.0 g/dL), renal function (creatinine clearance ≥50 mL/min calculated by Cockcroft-Gault formula), liver function (total bilirubin level ≤1.5 × ULN [except patients with documented Gilbert's syndrome] and serum transaminase levels ≤2.5 × ULN or ≤5 × ULN for liver metastasis and/or obstructive jaundice).
• Must have completed a duration of at least 4 weeks after stopping ICI therapy and must have recovered to grade ≤1 from all toxicities due to this therapy.
Exclusion Criteria:

• Has cardiac, hepatic, endocrine, pulmonary, or autoimmune disease, interstitial lung disease, renal or psychiatric disorders, not controlled with therapy corresponding to the illness or a condition that contraindicates the use of a taxane or an EGFR inhibitor.
• Has uncontrolled brain metastases. Patients are allowed if brain metastasis has been previously treated with surgery, whole brain irradiation, and/or stereotactic radiosurgery and are considered controlled (controlled by the dose ≤10 mg/day of prednisone or equivalent) at the time of the first dose of investigational product. Radiological evaluation of brain metastasis will be performed only if the patient has symptoms. For asymptomatic patients, brain imaging during screening is not required.
• Has baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval >480 milliseconds [CTCAE Grade 1] using Fredericia's QT correction formula).
• Has a history of additional risk factors for Torsade de pointes (eg, heart failure, hypokalemia, family history of long QT syndrome).
• Has had prior cetuximab therapy for recurrent or metastatic disease. Note that cetuximab used concomitantly with radiotherapy or as an induction therapy is acceptable
• Has received any other EGFR-targeted therapies for recurrent or metastatic disease.
• Currently participating in any clinical trial or receiving investigational therapy on expanded access or compassionate basis.
• Has nasopharyngeal carcinomas or salivary gland cancers.
• Has received investigational products or any other salvage therapy after failure of pembrolizumab/nivolumab therapy.
• Female patient who tested positive for pregnancy.
• Female patient who is breastfeeding or planning to become pregnant, or male patient planning to father a child within the duration of the study.
• Has tested positive for HIV, HBsAg, HCV antibody, or HCV RNA at screening. However, patients who test positive for HCV antibody, but negative for HCV RNA, will be allowed. In addition, patients with controlled HIV, chronic HBV on suppressive antiviral therapy, or a history of HCV infection status post-curative antiviral treatment with an HCV viral load below limit of quantification are permitted to participate (DHHS 2020).
• Has active infection requiring intravenous anti-infective therapy within 7 days prior to Day 1 Cycle 1 or is febrile due to infection.
• Has had major surgery within 4 weeks prior to screening.
• Administered a live attenuated vaccine within 4 weeks prior to Day 1 Cycle 1 or anticipation that such a live attenuated vaccine will be required during the study.
• Has known or suspected hypersensitivity to any components of the formulation used for this investigational product.
• Has concurrent disease or any clinically significant abnormality following the investigator's review of the screening physical examination findings, 12-lead ECG results, and clinical laboratory tests, which in the judgment of the investigator would interfere with the patient's participation in this study or evaluation of study results.
• Unable to come for study visits per schedule.
• Has current drug or alcohol abuse.
• Has received prior treatment with paclitaxel or docetaxel for metastatic or recurrent HNSCC. However, prior paclitaxel or docetaxel as a component of a curatively-intended multimodality treatment for locally advanced HNSCC is permitted.
Carcinoma, Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma, Lip, Oral Cavity and Pharynx, Head and Neck
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Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype (HARMONIA)

HARMONIA is an international, multicenter, randomized, open-label and phase III study. The primary objective of this study is to demonstrate that the combination of ribociclib with endocrine therapy (letrozole or fulvestrant) is superior to palbociclib with endocrine therapy (letrozole or fulvestrant) in prolonging progression-free survival in patients with advanced HR+/HER2- and HER2-E breast cancer. The study will enroll approximately 456 patients with HER2-E disease from approximately 95 sites worldwide. In addition, the HARMONIA trial will include an exploratory cohort of patients with HR+/HER2- and Basal-like disease treated with paclitaxel +/- Tislelizumab. This cohort does not have a predefined sample size and the objective is only exploratory, given the suggested lack of efficacy of the combinations of hormone therapy and CDK4/6 inhibitors in this subgroup of patients. Enrolment into the basal-like cohort will stop once the HER2-E disease cohort is fully enrolled.
Malinda West, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05207709
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Main
Inclusion Criteria:

• Histologically documented HR-positive and HER2-negative breast cancer by local testing
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer.
• Availability of FFPE tumor block for biomarker analysis, obtained during metastatic period.
• HER2-E or Basal-like subtype as per central PAM50 analysis.
• Measurable disease or non-measurable disease, as defined by RECIST v1.1
• Adequate hematologic and end-organ function
• Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
• Women of childbearing potential must have confirmed negative serum pregnancy test within 7 days prior to randomization.
• Women of CBP must be willing to use highly effective methods of contraception.
• Patient must have a 6-lead or 12-lead ECG with ALL of the following parameters at screening:
• QTcF interval (QT interval using Fridericia's correction) at screening < 450 msec.
• Resting heart rate 50-90 beats per minute (determined from the ECG). Main
Exclusion Criteria:

• Prior therapy with any CDK4/6 inhibitors.
• Patient has received prior treatment with chemotherapy for advanced/metastatic breast cancer
Metastatic Breast Cancer, Breast
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Study of DF9001 in Patients With Advanced Solid Tumors

DF9001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell activation signals to specific receptors on cancer cells. The study will occur in two phases. The first phase will be a dose escalation phase, enrolling patients with various types of solid tumors that express epidermal growth factor receptor (EGFR). The second phase will include a dose expansion using the best dose selected from the first phase of the study. Multiple cohorts will be opened with eligible patients having selected solid tumors (monotherapy and in combination with pembrolizumab).
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05597839
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Inclusion Criteria:
General (applies to all cohorts) 1. Signed written informed consent. 2. Male or female patients aged ≥ 18 years. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry and an estimated life expectancy of at least 3 months. 4. Adequate hematological function per protocol. 5. Adequate hepatic function per protocol. 6. Adequate renal function per protocol. 7. Participation in the use of contraception during the study, and for 150 days after the last dose of study drug for women of child-bearing potential (WOCBP) and 30 days after the last dose of study drug for male patients, as defined by the Clinical Trial Facilitation Group (CTFG) guidelines.
Inclusion Criteria:
Dose Escalation (Monotherapy) 1. Histologically proven locally advanced or metastatic solid tumors of epithelial origin that (1) have squamous NSCLC or HNSCC, (2) has documented EGFR protein expression or EGFR amplification or polysomy in their medical history from previous testing, or (3) test positive for EGFR expression via archival or fresh biopsy tissue prior to study enrollment using a validated immunohistochemistry (IHC) assay. 2. Evidence of objective disease, but participation does not require a measurable lesion.
Inclusion Criteria:
Head and Neck Squamous Cell Carcinoma (HNSCC) Expansion Cohorts 1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1. 2. Histologically documented relapsed or metastatic HNSCC. Primary tumor locations include oropharynx, oral cavity, hypopharynx, or larynx. Patients may not have a primary tumor site of nasopharynx (any histology). 3. Patients must have radiographic disease progression while on or after having received both platinum-based or fluoropyrimidine-based chemotherapy and an anti-PD-(L)1 therapy, administered either concurrent or sequentially. 4. Willing and able to provide the most recently available tissue blocks representing tumor biopsy obtained prior to treatment initiation. If recent tissue is not available, then a newly obtained baseline biopsy of an accessible tumor is required. Note that "recent" is defined as no intervening systemic anticancer therapies from the time of the last treatment of the prior therapy until screening for this trial. 5. Willing to undergo on-treatment biopsies, if safe and medically feasible.
Inclusion Criteria:
Renal Cell Carcinoma (RCC) Expansion Cohorts 1. Patients must have radiographic progression during treatment or after completing treatment for advanced (recurrent/unresectable/metastatic) disease or be intolerant to prior therapy. 2. Histologically documented relapsed or metastatic RCC that has documented EGFR expression or EGFR gene amplification or polysomy in their medical history from previous testing or test positive for EGFR expression (Section 6.2 EGFR Positivity) via archival (only if a block is available) or fresh biopsy tissue prior to study enrollment using a validated IHC assay. Cytology specimens cannot be used for the purpose of defining EGFR expression to meet eligibility. 3. Patients with clear cell RCC (ccRCC) must have radiographic progression after receipt of one of the following combination regimens as the preceding line of therapy: 1. PD-1/PD-L1-targeting mAb with or without a VEGFR-TKI. 2. PD-1-targeting mAb with a CTLA-4 monoclonal. 3. Patients with non-clear cell RCC (nccRCC) are not required to have received prior therapy in the metastatic setting. 4. Patients with RCC in general are not required to have received TKI therapy (eg, axitinib, cabozantinib, lenvatinib + everolimus, tivozanib). 4. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1. 5. Willing and able to provide the most recently available tissue blocks representing tumor biopsy obtained prior to treatment initiation. If recent tissue is not available, then a newly obtained baseline biopsy of an accessible tumor is required. Note that "recent" is defined as no intervening systemic anticancer therapies from the time of the last treatment of the prior therapy until screening for this trial. 6. Willing to undergo on-treatment biopsies, if safe and medically feasible.
Inclusion Criteria:
Non-Small Cell Lung Cancer (NSCLC) Expansion Cohorts 1. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IIIC, or stage IV NSCLC disease with or without actionable genomic alterations (AGA) (per the 7th IASLC classification of NSCLC), or recurrent disease. 1. Patients with squamous NSCLC do not require EGFR testing as part of this study to be eligible. 2. Non-squamous NSCLC patients who have documented EGFR expression or EGFR gene amplification or polysomy in their medical history from previous testing or test positive for EGFR expression (Section 6.2 EGFR Positivity) via archival (only if a block is available) or fresh biopsy tissue prior to study enrollment using a validated IHC assay. 3. Patients with stage IIIB or IIIC must be ineligible for local therapies with curative intent (eg, radiotherapy or surgery). 2. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1. 3. Patients must have recurrent or progressive disease during or after first line combination therapy with checkpoint inhibitors and platinum-based chemotherapy OR must have recurrent or progressive disease within 6 months after completing platinum- based chemotherapy for local disease, including those with actionable genetic alterations. They must not have received any subsequent lines of therapy. 4. Status for actionable mutations (EGFR, ALK, ROS1, RET, etc.) must be known (when testing is available as per country/region standard of care practices); patients with actionable mutations must have received and progressed on, have been intolerant to, or not be a candidate for standard TKIs (as available per country/region standard of care practices). 5. Willing and able to provide the most recently available tissue blocks representing tumor biopsy obtained prior to treatment initiation. If recent tissue is not available, then a newly obtained baseline biopsy of an accessible tumor is required. Note that "recent" is defined as no intervening systemic anticancer therapies from the time of the last treatment of the prior therapy until screening for this trial. 6. Willing to undergo on-treatment biopsies, if safe and medically feasible.
Exclusion Criteria:
1. Patients must not have had chemotherapy, radiotherapy (other than palliative bone- directed radiotherapy, as described in in exclusion criterion #2), or major surgery, or received another investigational agent within 28 days or 5 half-lives of the drug (if known), whichever is shorter, before the start of study treatment. 2. Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids. a. Note: Two weeks or fewer of palliative radiotherapy for non-central nervous system (CNS) disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention. 3. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention. 4. Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy [except for palliative bone-directed radiotherapy, which is not a target lesion], immune therapy, or cytokine therapy [except for erythropoietin]), major surgery (excluding prior diagnostic biopsy), concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days or 5 half-lives of the drug (if known), whichever is shorter, before the start of study treatment. Short-term administration of systemic steroids (eg, for allergic reactions or the management of irAEs) is allowed. Note: Patients receiving bisphosphonate or denosumab are eligible, provided treatment was initiated at least 14 days before the first dose of DF9001. 5. Previous malignant disease other than the target malignancy to be investigated in this study within the last 3 years. Exceptions (eg, basal or squamous cell carcinoma of the skin, or cervical carcinoma in situ) can be considered on a case-by-case basis, in consultation with the Medical Monitor. 6. Life expectancy of less than 6 months. 7. Receipt of any organ transplantation, including autologous or allogeneic stem-cell transplantation. 8. Significant acute or chronic infections (including historic positive test for human immunodeficiency virus [HIV], or active or latent hepatitis B or active hepatitis C tested during the screening window). If HBsAg is negative and the anti-hepatitis B core antibody is positive, then hepatitis B viral DNA load must be undetectable. 9. 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, dysgammaglobulinemia or congenital immunodeficiencies). Patients with a history of immune-related endocrinopathies (eg, hypothyroidism, type 1 diabetes mellitus [TIDM], and adrenal insufficiency) that are stable on hormone replacement therapy may be eligible for this study. 10. Patients with a known medical history that may place them at risk of known toxicities of EGFR blockade. 1. History of or ongoing keratitis, ulcerative keratitis, or corneal perforation. 2. History of cardiopulmonary arrest unless this was caused by an acute, reversible etiology that is no longer present. 3. History of or ongoing pulmonary fibrosis or interstitial lung disease. 11. Known severe hypersensitivity reactions to mAbs (≥ Grade 3 of the NCI-CTCAE v5.0), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partly controlled asthma). 12. Persisting toxicity related to prior therapy >Grade 1 NCI-CTCAE v5.0; however, alopecia ≤Grade 2, endocrinopathies ≤Grade 2, and sensory neuropathy ≤ Grade 2 is acceptable. 13. Patients who have received an anti-PD-(L)1 as a previous line of therapy that have experienced either of the following: 1. a Grade 3 or Grade 4 drug-related toxicity. 2. a Grade 2 drug-related toxicity that impacted either the lungs, cardiac, or the nervous system, caused by the administration of the anti-PD-(L)1. 14. Received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis. 15. A WOCBP 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. 16. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Administration of killed vaccines are allowed. 17. Pregnancy or lactation in females during the study. 18. Known alcohol or drug abuse. 19. Serious cardiac illness or medical conditions, including but not limited to: 1. History of New York Heart Association class III or IV heart failure or systolic dysfunction (left ventricular ejection fraction [LVEF] <55%). 2. High-risk uncontrolled arrhythmias (eg, tachycardia with a heart rate >100/min at rest). 3. Significant ventricular arrhythmia (ventricular tachycardia) or higher-grade atrioventricular (AV) block (eg, AV-block, second degree AV block Type 2 [Mobitz 2], or third-degree AV-block). 4. Angina pectoris requiring anti-anginal medication. 5. Clinically significant valvular heart disease. 6. Evidence of transmural infarction on electrocardiograms (ECGs). 7. Poorly controlled hypertension (defined as systolic >160 mm Hg or diastolic >100 mm Hg). 8. 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. 9. Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy. 20. All other significant diseases (eg, inflammatory bowel disease), which, in the opinion of the Investigator, might impair the patient's ability to participate. 21. Any psychiatric condition that would prohibit the understanding or rendering of informed consent. 22. Legal incapacity or limited legal capacity. 23. Incapable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 24. Has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study treatment (for NSCLC cohorts only). 25. Patients with brain metastases, unless all of the following criteria are met: 1. CNS lesions are asymptomatic, previously treated and no active therapy is required (ie, no corticosteroids for edema), 2. Radiologically stable (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during the study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study intervention. 3. Imaging demonstrates stability of disease 28 days from last treatment for CNS metastases. 26. Active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid). 27. Patients with leptomeningeal disease are excluded. 28. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 29. Active infection requiring systemic therapy. 30. Severe hypersensitivity (≥Grade 3) to pembrolizumab, and/or any of its excipients.
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus, Solid Tumor, Adult
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Testing Radiation and HER2-targeted Therapy Versus HER2-targeted Therapy Alone for Low-risk HER2-positive Breast Cancer (HERO)

This Phase III trial compares the recurrence-free interval (RFI) among patients with early-stage, low risk HER2+ breast cancer who undergo breast conserving surgery and receive HER2-directed therapy, and are randomized to not receive adjuvant breast radiotherapy versus those who are randomized to receive adjuvant radiotherapy per the standard of care.
Bethany Anderson, MD
All
40 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05705401
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Inclusion Criteria:

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
• female and male patients who have undergone breast conserving surgery and completed a minimum of 4 cycles (12 weeks) of neoadjuvant or adjuvant chemotherapy in combination with HER2-targeted therapy. -≥ 40 years of age
• ECOG performance status of 0 ,1, or 2/Karnofsky performance status above 60
• Histologically or cytologically confirmed invasive breast carcinoma.
• tumor must have been determined to be HER2-positive by current ASCO/CAP guidelines based on local testing results.
• Patient must have undergone axillary staging, either sentinel node biopsy (SNB) or axillary lymph nodal dissection (ALND). In neoadjuvant patients, SNB following neoadjuvant therapy is strongly recommended. SNB prior to neoadjuvant therapy is discouraged, but patients are permitted if node negative (pN0).
• The following staging criteria must be met according to AJCC 8th edition criteria: Adjuvant cohort : By pathologic evaluation, the patient's primary tumor must be • For the Adjuvant cohort, adjuvant therapy must have consisted of a minimum of 4 cycles (12 weeks) of chemotherapy in combination with HER2-targeted therapy.
• For the Neoadjuvant cohort, neoadjuvant therapy must have consisted of a minimum of 4 cycles (12 weeks) of chemotherapy in combination with HER2-targeted therapy.- ; Patients who did not receive chemotherapy in the neoadjuvant setting are not eligible, even if they achieved pCR with their preoperative treatment; nor would these patients become eligible by receiving chemotherapy after surgery.
• In patients assigned to radiation therapy, treatment should start ≤ 12 weeks from surgery on the Neoadjuvant cohort and ≤ 8 weeks from the completion of chemotherapy on the Adjuvant cohort. Patients should continue HER2-targeted therapy during assigned study treatment (radiation or observation).
• Bilateral mammogram or MRI within 52 weeks prior to randomization.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial.
Exclusion Criteria:

• Definitive clinical or radiologic evidence of metastatic disease.
• On the Adjuvant cohort, patients with a primary tumor >2 cm on pathologic examination of the surgical specimen. On the Neoadjuvant cohort, patients with a primary tumor > 3 cm or with abnormal or suspicious ipsilateral axillary nodes by pretreatment imaging, unless demonstrated to be negative by cytologic or histologic examination.
• Pathologically positive axillary nodes at any time including of pN0(i+) or pN0(mol+) ypN0(i+) or ypN0(mol+) disease.
• Patient planning for or status-post mastectomy.
• Radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary lymph nodes, unless there is histological confirmation that these nodes are negative for metastatic disease.
• Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast), or mass or non-mass enhancement on MRI (if performed) aside from the known cancer, unless biopsied and found to be benign.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by > 4 centimeters. If multifocal, all foci should be confined to a maximum tumor bed of 3 cm determined by pathological assessment.
• Paget's disease of the nipple.
• Synchronous (unilateral or bilateral) invasive breast cancer or DCIS. (Patients with synchronous and/or previous contralateral LCIS are eligible.)
• On the Adjuvant cohort, surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re-excision, the patient is eligible).
• Treatment plan that includes regional nodal irradiation.
• Patients treated for a prior invasive breast malignancy are excluded. Contralateral DCIS ≥ 10 years prior to enrollment is permissible.
• 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 on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible unless discontinued prior to randomization.
• Prior ipsilateral breast or thoracic RT for any condition (contralateral RT for DCIS ≥ 10 years prior to randomization is permitted).
• Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active systemic lupus erythematosus, or scleroderma.
• Clinicians should consider whether any conditions would make this protocol unreasonably hazardous for the patient.
• Pregnancy or lactation at the time of randomization or intention to become pregnant during treatment. (Note: Pregnancy testing according to institutional standards for patients of childbearing potential must be performed within 14 days prior to randomization.)
• Use of any investigational product within 30 days prior to randomization.
HER2-positive Breast Cancer, Breast
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Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma (XPORT-EC-042)

The purpose of this study is to evaluate the efficacy and safety of selinexor as a maintenance treatment in patients with p53 wt endometrial carcinoma (EC), who have achieved a partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v 1.1]) after completing at least 12 weeks of platinum-based therapy. A total of 220 participants will be enrolled in the study and randomized in a 1:1 ratio to maintenance therapy with either selinexor or placebo.
Ellen Hartenbach, M.D.
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05611931
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Inclusion Criteria:

• At least 18 years of age at the time of signing informed consent.
• Histologically confirmed EC including: endometrioid, serous, undifferentiated, and carcinosarcoma.
• TP53 wt assessed by next generation sequencing (NGS), evaluated by a central vendor.
• Completed a single line, at least 12 weeks of platinum-based therapy (not including adjuvant or neoadjuvant therapy for Stage I-III disease) and achieved confirmed partial or complete response (PR or CR) by imaging, according to RECIST version 1.1. The participants should have received treatment for: Primary Stage IV disease, defined as:
• had a primary or later debulking surgery during first-line platinum-based therapy with R0 resection (R0 resection indicates a macroscopic complete resection of all visible tumor) and achieved CR after at least 12 weeks platinum-based therapy, OR
• had a primary or later debulking surgery during first-line platinum-based therapy with R1 resection (R1 resection indicates incomplete removal of all macroscopic disease) and achieved PR or CR after at least 12 weeks platinum-based chemotherapy, OR
• had no surgery and achieved PR or CR after at least 12 weeks platinum-based chemotherapy OR At first relapse (i.e., relapse after primary therapy including surgery and/or chemotherapy and/or immunotherapy for Stage I-IV disease), defined as:
• had Stage I
•III disease at diagnosis and received, at initial diagnosis, adjuvant chemotherapy and relapsed later. Participants should have PR or CR after at least 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse,
• had Stage I-III disease at diagnosis and did not receive adjuvant chemotherapy at initial diagnosis and relapsed later. Participants should have PR or CR after at least 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse, OR
• had Stage IV disease at diagnosis and received initially chemotherapy with or without surgery and relapsed later. At the time of relapse, participants should have PR or CR after at least 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse.
• Previous treatment with anti-programmed cell death protein 1(PD-1) or anti-programmed death-ligand 1(PD-L1) monoclonal antibody and concomitant biologic agents (e.g., bevacizumab, trastuzumab) is allowed.
• Must be able to initiate study drug 3 to 8 weeks after completion of their final dose of chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Participants must have adequate bone marrow function and organ function within 2 weeks before starting study drug as defined by the following laboratory criteria:
• Hepatic function: total bilirubin up to less than (<) 3*upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (<=) 2.5*ULN in participants without liver metastasis. For participants with known liver involvement of their tumor: AST and ALT (<=) 5*ULN
• Hematopoietic function within 1 week: Absolute neutrophil count (ANC) greater than or equal to (>=) 1.5*10^9/liter (L); platelet count >= 100*10^9/L; hemoglobin >= 9.0 gram per deciliter (g/dL) per local laboratory results
• Renal function: estimated creatinine clearance (CrCl) of >= 20 milliliter per minute (mL/min), calculated using the standard local formula, as applicable
•In the opinion of the Investigator, the participant must:
• Have a life expectancy of at least 12 weeks, and
• Be fit to receive investigational therapy
• Premenopausal females of childbearing potential must have a negative pregnancy test (serum β-human chorionic gonadotropin test) prior to the first dose of study drug. Female participants of childbearing potential must agree to use highly effective methods of contraception throughout the study and for 90 days following the last dose of study drug.
• Written informed consent signed in accordance with federal, local, and institutional guidelines prior to the first screening procedure.
Exclusion Criteria:

• Participants meeting any of the following exclusion criteria are not eligible to enroll in this study:
• Has any uterine sarcomas (carcinosarcomas
•not excluded), clear cell or small cell carcinoma with neuroendocrine differentiation
• Received a blood or platelet transfusion during the 2 weeks prior to Cycle 1 Day 1 (C1D1). Participants' hemoglobin must be assessed within 2 weeks of screening and at least 1 week post transfusion
• Concurrent systemic steroid therapy higher than physiologic dose (> 10 milligram per day [mg/day] of prednisone or equivalent). Systemic steroid therapy as pre-medication for taxane is allowed
• Insufficient time since or not recovered from procedures or anti-cancer therapy, defined as:
• Not recovered from major surgery <= 28 days prior to Day 1 dosing. Minor procedures, such as biopsies, dental work, or placement of a port or intravenous (IV) line for infusion are permitted
• Having ongoing clinically significant anti-cancer therapy-related toxicities CTCAE Grade > 1, with the exception of alopecia. In specific cases, participants whose toxicity has stabilized or with Grade 2 non-hematologic toxicities can be allowed following documented approval by the Sponsor's Medical Monitor
• Palliative radiotherapy within 14 days of the intended C1D1. Palliative radiotherapy may be permitted for symptomatic control of pain from bone metastases, provided that the radiotherapy does not involve target lesions, and the reason for the radiotherapy does not reflect evidence of disease progression.
• Any gastrointestinal dysfunctions that could interfere with the absorption of selinexor (e.g., bowel obstruction, inability to swallow tablets, malabsorption syndrome, unresolved nausea, vomiting, diarrhea CTCAE v 5.0 > grade 1).
• Participants unable to tolerate two forms of antiemetics for at least 2 cycles will not be eligible for the trial.
• Active, ongoing or uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week of screening.
• Serious psychiatric or medical condition that could interfere with participation in the study or in the opinion of the Investigator would make study involvement unreasonably hazardous.
• Previous treatment with an XPO1 inhibitor.
• Stable disease or PD on the post-chemotherapy scan or clinical evidence of progression prior to randomization.
• Participants who received any systemic anticancer therapy including investigational agents <= 3 weeks (or <= 5 half-lives of the drug [whichever is shorter]) prior to C1D1.
• Major injuries or surgery within 14 days prior to C1D1 and/or planned major surgery during the on-treatment study period.
• Other malignant disease with disease-free <= 3 years except: curatively treated carcinoma in situ of the cervix, basal cell carcinoma of the skin, or ductal carcinoma in situ (DCIS) of the breast.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor, or other agents used in the study.
• Active brain metastases (e.g., stable for < 8 weeks, no adequate previous treatment with radiotherapy and/or surgery, symptomatic, requiring treatment with anti-convulsant therapy. Corticoid therapy is allowed if administered as stable dose for at least 1 month before randomization).
• Females who are pregnant or lactating.
• Any other life-threatening illness, active medical condition, organ system dysfunction, or serious active psychiatric issue which, in the Investigator's opinion, could compromise the participant's safety or the participant's ability to remain compliant with study procedures.
Corpus Uteri, Uterus, Endometrial Cancer
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A Trial Comparing Unrelated Donor BMT With IST for Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202) (TransIT)

Severe Aplastic Anemia (SAA) is a rare condition in which the body stops producing enough new blood cells. SAA can be cured with immune suppressive therapy or a bone marrow transplant. Regular treatment for patients with aplastic anemia who have a matched sibling (brother or sister), or family donor is a bone marrow transplant. Patients without a matched family donor normally are treated with immune suppressive therapy (IST). Match unrelated donor (URD) bone marrow transplant (BMT) is used as a secondary treatment in patients who did not get better with IST, had their disease come back, or a new worse disease replaced it (like leukemia). This trial will compare time from randomization to failure of treatment or death from any cause of IST versus URD BMT when used as initial therapy to treat SAA. The trial will also assess whether health-related quality of life and early markers of fertility differ between those randomized to URD BMT or IST, as well as assess the presence of marrow failure-related genes and presence of gene mutations associated with MDS or leukemia and the change in gene signatures after treatment in both study arms. This study treatment does not include any investigational drugs. The medicines and procedures in this study are standard for treatment of SAA.
Kenneth Desantes, M.D.
All
0 Years to 25 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05600426
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Inclusion Criteria:
To be eligible to participate in the randomized trial, an individual must meet all the following criteria: 1. Provision of signed and dated informed consent form for the randomized trial by patient and/or legal guardian. 2. Age ≤25 years old at time of randomized trial consent. 3. Confirmed diagnosis of idiopathic SAA, defined as: 1. Bone marrow cellularity <25%, or <30% hematopoietic cells. 2. Two of three of the following (in peripheral blood): neutrophils <0.5 x 10^9/L, platelets <20 x 10^9/L, absolute reticulocyte count <60 x 10^9/L or hemoglobin <8 g/dL. 4. No suitable fully matched related donor available (minimum 6/6 match for HLA-A and B at intermediate or high resolution and DRB1 at high resolution using DNA based typing). 5. At least 2 unrelated donors noted on NMDP search who are well matched (9/10 or 10/10 for HLA-A, B, C, DRB1, and DQB1 using high resolution). 6. In the treating physician's opinion, no obvious contraindications precluding them from BMT or IST.
Exclusion Criteria:
1. Presence of Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow. Telomere length testing should be sent on all patients to exclude Dyskeratosis Congenita (DC), but if results are delayed or unavailable and there are no clinical manifestations of DC, patients may enroll. If patients have clinical characteristics suspicious for Shwachman-Diamond syndrome, this disorder should be excluded by pancreatic isoamylase testing or gene mutation analysis (note: pancreatic isoamylase testing is not useful in children <3). Other testing per center may be performed to exclude IBMFS. 2. Clonal cytogenetic abnormalities or Fluorescence In-Situ Hybridization (FISH) pattern consistent with pre- myelodysplastic syndrome (pre-MDS) or MDS on marrow examination. 3. Known severe allergy to ATG. 4. Prior allogeneic or autologous stem cell transplant. 5. Prior solid organ transplant. 6. Infection with human immunodeficiency virus (HIV). 7. Active Hepatitis B or C. This only needs to be excluded in patients where there is clinical suspicion of hepatitis (e.g., elevated LFTs). 8. Female patients who are pregnant or breast-feeding. 9. Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. 10. Disease modifying treatment prior to study enrollment, including but not limited to use of androgens, eltrombopag, romiplostim, or immune suppression. Note: Supportive care measures such as G-CSF, blood transfusion support and antibiotics are allowable
Severe Aplastic Anemia, Other Hematopoietic, Hematologic cancers, other
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Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Study (SAMURAI)

This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread to other places in the body (metastatic). Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.
Hamid Emamekhoo, M.D.
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05327686
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Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration
• Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:
• History/physical examination within 45 days prior to registration
• CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration
• Patients must have IMDC intermediate (1-2 factors) or poor risk disease (>= 3 factors)
• 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 measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor
• Patient not recommended for or refused immediate cytoreductive nephrectomy
• Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen
• Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging
• Age >= 18
• Karnofsky performance status >= 60 within 45 days prior to registration
• Hemoglobin >= 8 g/dL (transfusions are allowed) (within 45 days prior to registration)
• Platelet count >= 50,000/mm^3 (within 45 days prior to registration)
• Absolute neutrophil count (ANC) >= 1500/mm^3 (within 45 days prior to registration)
• Calculated (Calc.) creatinine clearance >= 30 mL/min (within 45 days prior to registration)
• For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) (within 45 days prior to registration)
• Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =< 3 x upper limit of normal (ULN) or < 5 x ULN if hepatic metastases present (within 45 days prior to registration)
• Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol
• 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. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
• The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. 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
• 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 planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment
• Patients with untreated or unstable brain metastases or cranial epidural disease
• Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
• Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor
• Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated > 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration)
• Severe, active comorbidity defined as follows:
• Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
• Active tuberculosis (purified protein derivative [PPD] response without active tuberculosis [TB] is allowed)
• Uncontrolled hypertension (systolic blood pressure [BP] > 190 mmHg or diastolic BP > 110 mmHg)
• Major surgery requiring hospital admission ≤ 28 days prior to registration.
• Any serious (requiring hospital stay or long-term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration
• Any arterial thrombotic (ST elevation myocardial infarction [STEMI], non-ST elevation myocardial infarction [NSTEMI], cerebrovascular accident [CVA], etc) events within 180 days prior to registration
• Active New York (NY) Heart Association class 3-4 heart failure symptoms
• Moderate or severe hepatic impairment (Child-Pugh B or C)
• Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis > 30 days prior to registration is allowed)
• Unstable cardiac arrhythmia within 180 days prior to registration
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration
• History of or active inflammatory bowel disease
• Malabsorption syndrome within 45 days prior to registration
• Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =< 45 days prior to registration
Metastatic Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Unresectable Renal Cell Carcinoma, Kidney
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Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma

This phase II trial studies the effect of duvelisib or CC-486 and usual chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone in treating patients with peripheral T-cell lymphoma. Duvelisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as CC-486, cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone, 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 help find out if this approach is better or worse than the usual approach for treating peripheral T-cell lymphoma.
Saurabh Rajguru, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04803201
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Inclusion Criteria:

• Histologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) with < 10% CD30 expression by immunohistochemistry in the following subtypes (by local review): nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (TFH-PTCL), follicular T-cell lymphoma, PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), enteropathy associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma
• Patients with expression of CD30 in >= 10% of the tumor (based on local immunohistochemistry review) regardless of histology will not be permitted
• Patients with a diagnosis of other PTCL subtype histologies other than those specified in the inclusion criteria are excluded including large cell transformation of mycosis fungoides
• Patients will be stratified by presence or absence of TFH phenotype (i.e. diagnosis of AITL, TFH-PTCL, follicular T-cell lymphoma) based on local review of pathology. Determination of TFH phenotype can be defined by expression of two or more of the following markers CD10, BCL6, CXCL13, ICOS, and PD1 by immunohistochemistry
• Measurable disease as defined by the Lugano criteria
• No prior systemic therapy for lymphoma (excluding corticosteroids)
• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =< 7 days prior to registration is required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Platelet count >= 75,000/mm^3 (>= 50,000/mm^3 if secondary to bone marrow involvement from lymphoma per investigator assessment; the first 12 patients on each arm of the study must have platelets >= 75,000/mm^3 regardless of bone marrow involvement)
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3.0 x upper limit of normal (ULN) * Except in subjects with documented liver involvement by lymphoma
• Calculated creatinine clearance >= 30 mL/min by Cockcroft-Gault formula
• Total bilirubin =< 2.0 x ULN * Except in cases of Gilbert's Syndrome or documented liver or pancreatic involvement by lymphoma
• Archival tissue must be available for submission
• Patients known to have HTLV 1/2 are excluded
• Patients with known central nervous system involvement are excluded
• No active viral infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. Those who are seropositive (e.g. hepatitis B core antibody [Ab] positive) are permitted if they are negative by polymerase chain reaction (PCR). Those who are seropositive for hepatitis B and are negative for hepatitis B virus (HBV) deoxyribonucleic acid (DNA) by PCR must receive concomitant hepatitis B directed antiviral therapy. Those who have hepatitis C Ab positivity who have completed curative therapy for hepatitis C with negative hepatitis C PCR are eligible
• Patients with history of HIV are eligible if they have an undetectable viral load for at least 6 months
• No active uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment). Patients with Epstein-Barr virus (EBV) viremia related to their lymphoma are permitted
• No concurrent malignancy requiring active therapy within the last 3 years with the exception of basal cell carcinoma limited to the skin, squamous cell carcinoma limited to the skin, carcinoma in situ of the cervix, breast or localized prostate cancer. Adjuvant hormonal therapy for cancer previously treated for curative intent is permitted
• Patients must have documented left ventricular ejection fraction of >= 45%
• No significant active cardiac disease within the previous 6 months including:
• New York Heart Association (NYHA) class III or IV congestive heart failure
• Unstable angina or angina requiring surgical or medical intervention; and/or
• Myocardial infarction
• No contraindication to any drug in the chemotherapy regimen, including neuropathy >= grade 2
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
Angioimmunoblastic T-cell Lymphoma, Enteropathy-Associated T-Cell Lymphoma, Follicular T-Cell Lymphoma, Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma, Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma, Nodal Peripheral T-Cell Lymphoma With TFH Phenotype, Peripheral T-Cell Lymphoma, Not Otherwise Specified, Non-Hodgkin's Lymphoma, Lymphoma
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Testing the Addition of Whole Brain Radiotherapy Using a Technique That Avoids the Hippocampus to Stereotactic Radiosurgery in People With Cancer That Has Spread to the Brain and Come Back in Other Areas of the Brain After Earlier Stereotactic Radiosurgery

This phase III trial compares the effect of adding whole brain radiotherapy with hippocampal avoidance and memantine to stereotactic radiosurgery versus stereotactic radiosurgery alone in treating patients with cancer that has spread to the brain and come back in other areas of the brain after earlier stereotactic radiosurgery. Hippocampus avoidance during whole-brain radiation therapy decreases the amount of radiation that is delivered to the hippocampus, which is a brain structure that is important for memory. The medicine memantine is also often given with whole brain radiation therapy because it may decrease the risk of side effects of radiation on thinking and memory. Stereotactic radiosurgery delivers a high dose of radiation only to the small areas of cancer in the brain and avoids the surrounding normal brain tissue. Adding whole brain radiotherapy with hippocampal avoidance and memantine to stereotactic radiosurgery may be effective in shrinking or stabilizing cancer that has spread to the brain and returned in other areas of the brain after receiving stereotactic radiosurgery.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04588246
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Inclusion Criteria:

• Patients must have developed their first or second distant brain relapse(s) at least 8 weeks after upfront SRS and within 21 days prior to randomization
• Distant brain relapse lesions to be treated must measure =< 3.0 cm in maximal extent and total volume of distant brain relapses to be treated must measure < 30 mL on the contrast-enhanced diagnostic magnetic resonance imaging (MRI) brain scan obtained within 21 days prior to randomization
• Distant brain relapse lesions must be diagnosed on MRI, which will include the following elements:
• REQUIRED MRI ELEMENTS
• Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D) spoiled gradient (SPGR). Acceptable 3D SPGR sequences include magnetization-prepared 3D gradient recalled echo (GRE) rapid gradient echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (brain volume imaging) or 3D fast FE (field echo). The T1-weighted 3D scan should use the smallest possible axial slice thickness, not to exceed 1.5 mm
• Pre-contrast T1 weighted imaging (3D imaging sequence strongly encouraged)
• A minimum of one axial T2 fluid attenuated inversion recovery (FLAIR) (preferred) or T2 sequence is required. This can be acquired as a 2D or 3D image. If 2D, the images should be obtained in the axial plane
• ADDITIONAL RECOMMENDATIONS
• Recommendation is that an axial T2 FLAIR (preferred) sequence be performed instead of a T2 sequence
• Recommendation is that that pre-contrast 3D T1 be performed with the same parameters as the post-contrast 3D T1
• Recommendation is that imaging be performed on a 3 Tesla (3T) MRI
• Recommendation is that the study participants be scanned on the same MRI instrument at each time point
• Recommendation is that if additional sequences are obtained, these should meet the criteria outlined in Kaufmann et al., 2020
• If additional sequences are obtained, total imaging time should not exceed 60 minutes
• Brain metastasis velocity (BMV) since upfront SRS must be >= 4 brain metastases/year
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
• Pathologically (histologically or cytologically) proven diagnosis of non-small cell lung cancer, melanoma, breast cancer, renal cell carcinoma, or gastrointestinal cancer within 10 years prior to randomization. If the original histologic proof of malignancy is greater than 10 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic metastasis or brain metastasis)
• Other histologies are not permitted
• History and physical examination within 28 days prior to randomization
• Karnofsky performance status of >= 70 within 28 days prior to randomization
• Calculated creatinine clearance (CrCl) >= 30 ml/min (within 28 days prior to randomization)
• Blood urea nitrogen (BUN) within 1.5 times the institutional upper limit of normal (ULN) (e.g., if the ULN is 20 mg/dL, then BUN up to 30 mg/dL is permitted) (within 28 days prior to randomization)
• Negative urine or serum pregnancy test (in women of childbearing potential) within 14 days prior to randomization
Exclusion Criteria:

• Prior WBRT or prophylactic cranial irradiation
• Local relapse of metastasis previously treated with upfront SRS (i.e., relapse outside previously SRS-treated metastases is allowed)
• Brain metastases from primary germ cell tumor, small cell carcinoma, or lymphoma
• Definitive leptomeningeal metastasis
• Planned cytotoxic chemotherapy on the same day as SRS or HA-WBRT; concurrent immunotherapy is permitted
• Radiographic evidence of enlargement or other architectural distortion of the lateral ventricles, including placement of external ventricular drain or ventriculoperitoneal shunt
• Known history of demyelinating disease such as multiple sclerosis
• Inability to swallow pills
• Contraindication to MR imaging such as non-MR conditional implanted metal devices or unknown metallic foreign bodies, or contraindication to gadolinium contrast administration during MR imaging, such as anaphylactic allergy that cannot be adequately addressed with pre-contrast medications or acute kidney injury
• Contraindications to memantine, including:
• Allergy, including prior allergic reaction to memantine
• Intractable seizures on adequate anticonvulsive therapy-more than 1 seizure per month for the past 2 months
• Current use of N-methyl-D-aspartate (NMDA) agonist
• Current alcohol or drug abuse, which can exacerbate lethargy/dizziness with memantine
• Severe, active co-morbidity defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of randomization
• Chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy at the time of randomization
• Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic disease
• Renal tubular acidosis or metabolic acidosis
• Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to randomization. Note also that HIV testing is not required for eligibility for this protocol
• Pregnant or lactating women, or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the medication and radiation involved in this study has unknown effects on the unborn fetus
Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Metastatic Digestive System Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Metastatic Melanoma, Metastatic Renal Cell Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8, Recurrent Brain Neoplasm, Stage IV Lung Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8, Brain and Nervous System, Brain/Central Nervous System
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Melanoma Margins Trial-II: 1cm v 2cm Wide Surgical Excision Margins for AJCC Stage II Primary Cutaneous Melanoma (MelMarT-II)

Patients with a primary invasive melanoma are recommended to undergo excision of the primary lesion with a wide margin. There is evidence that less radical margins of excision may be just as safe. This is a randomised controlled trial of 1 cm versus 2 cm margin of excision of the primary lesion for adult patients with stage II primary invasive cutaneous melanomas (AJCC 8th edition) to determine differences in disease-free survival. A reduction in margins is expected to improve patient quality of life.
Heather Neuman, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03860883
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Inclusion Criteria:
1. Patients must have a stage II primary invasive cutaneous melanoma with Breslow thickness >2mm without ulceration), or >1mm (with ulceration only) (pT2b-pT4b, AJCC 8th edition) as determined by diagnostic biopsy (narrow excision, incision or punch biopsy) and subsequent histopathological analysis. 2. Must have a primary melanoma that is cutaneous (including head, neck, trunk, extremity, scalp, palm or sole). 3. An uninterrupted 2cm margin must be technically feasible around biopsy scar or primary melanoma. 4. Surgery (which refers to the staging sentinel node biopsy and wide local excision as these are both to be done on the same day) must be completed within 120 days of the original diagnosis. 5. Patients must be 18 years or older at time of consent. 6. Patient must be able to give informed consent and comply with the treatment protocol and follow-up plan. 7. Life expectancy of at least 5 years from the time of diagnosis, not considering the melanoma in question, as determined by the PI. 8. Patients must have an ECOG performance score between 0 and 1. 9. A survivor of prior cancer is eligible provided that ALL of the following criteria are met and documented:
• The patient has undergone potentially curative therapy for all prior malignancies,
• There has been no evidence of recurrence of any prior malignancies for at least FIVE years (except for successfully treated cervical or non-melanoma skin cancer with no evidence of recurrence), and
• The patient is deemed by their treating physician to be at low risk of recurrence from previous malignancies.
Exclusion Criteria:
Patients will be excluded from the study for ANY of the following reasons: 1. Uncertain diagnosis of melanoma i.e. so-called 'melanocytic lesion of unknown malignant potential'. 2. Patient has already undergone wide local excision at the site of the primary index lesion. 3. Patient unable or ineligible to undergo staging sentinel lymph node biopsy of the primary index lesion. 4. Desmoplastic or neurotropic melanoma: with any patient where pathology determines melanoma as PURE desmoplastic (as per WHO definition of >90% desmoplasia), they are not eligible for this study. However other desmoplasia or mixed subtypes are eligible unless there is neurotropism present (peri-neural invasion).Peri-neural invasion does not include entrapment of nerves within the main primary tumour mass. Microsatellitosis as per AJCC 8th edition definition 5. Subungual melanoma 6. Patient has already undergone a local flap reconstruction of the defect after excision of the primary and determination of an accurate excision margin is impossible. 7. History of previous or concurrent (i.e., second primary) invasive melanoma. 8. Melanoma located distal to the metacarpophalangeal joint; on the tip of the nose; the eyelids or on the ear; genitalia, perineum or anus; mucous membranes or internal viscera. 9. Physical, clinical, radiographic or pathologic evidence of satellite, in-transit, regional, or distant metastatic melanoma. 10. Patient has undergone surgery on a separate occasion to clear the lymph nodes of the probable draining lymphatic field, including sentinel lymph node biopsy, of the index melanoma. 11. Any additional solid tumour or hematologic malignancy during the past 5 years except T1 skin lesions of squamous cell carcinoma, basal cell carcinoma, or uterine/cervical cancer. 12. Melanoma-related operative procedures not corresponding to criteria described in the protocol. 13. Planned adjuvant radiotherapy to the primary melanoma site after Wide Local Excision is not permitted as part of the protocol and any patients given this treatment would be excluded from the study. 14. History of organ transplantation. 15. Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) at enrolment or within 6 months prior to enrolment. Pregnancy is not a specific exclusion criterion for this trial, though it may not be clinically appropriate to perform a wide excision and sentinel node biopsy until the pregnancy has been completed, which is likely to exclude the patient due to violation of inclusion criterion 4. We would advise careful counselling of the patient prior to enrolling the patient, which would include a discussion at the treating centre's multidisciplinary team meeting or tumour board. We would strongly advise contacting the central trial office to discuss the case prior to enrolling on the study.
Cutaneous Melanoma, Stage II, Melanoma, Skin, Melanoma/Skin cancer
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