Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
Фаза 2 – изследване на ефективността и дозировката
Заболявания:
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
Спонсор: National Cancer Institute (NCI)
Налично на:
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Обобщение
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.
Описание
PRIMARY OBJECTIVE:
I. To register, allocate, and assign patients to ComboMATCH treatment trials.
SECONDARY OBJECTIVES:
I. To evaluate the rate of positive outcomes in defined cohorts within treatment trials of treatment combinations including targeted therapies for molecularly defined populations, and also in the subset of treatment trials where the treatments are supported by in vivo models.
II. To perform quality control of the patients registered in the form of pathological confirmation of disease and sub-type to confirm diagnosis and treatment arm allocation.
SECONDARY CORRELATIVE OBJECTIVES:
I. Assess the concordance of the central molecular characterization of the pre-treatment biopsy samples with the genetic readouts from the Designated Laboratories (DLs) for patients enrolled on the ComboMATCH treatment trials.
II. To assess how the registration diagnostic tumor mutation profile and pre-treatment biopsy profile compare to the circulating tumor-derived deoxyribonucleic acid (ctDNA) mutation profile from plasma.
EXPLORATORY OBJECTIVE:
I. Assess association between ComboMATCH treatment trials outcomes (positive or negative) with the type of rationale for the selected drug combinations and the type of rationale for the gene variant/combination for selection (e.g., whether the trial was based on targeted therapies for molecularly defined populations, those that were supported by in vivo models, and those that were supported by empiric clinical data).
OUTLINE:
REGISTRATION: Patients undergo tumor mutational screening of previously-collected tumor samples for specific, pre-defined mutations, amplifications, or translocations of interest via tumor sequencing. Patients who are 18 years or older and have biopsiable disease undergo a new biopsy for research purposes prior to initiating treatment on the ComboMATCH treatment trial.
TREATMENT: Patients with mutations targeted to investigational combination therapies are assigned to 1 of 20 treatment subprotocols.
EAY191-N4: Patients with RAS pathway mutant ovarian or endometrial cancer are randomized to 1 of 2 arms.
ARM I: Patients receive selumetinib orally (PO) twice daily (BID) and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as echocardiogram (ECHO) or multigated acquisition (MUGA), and computed tomography (CT) scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.
ARM II: Patients receive selumetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO
Кой може да участва
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
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