Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

Brief summary public domain (ClinicalTrials.gov)

This phase II MATCH screening and multi-sub-trial studies how well treatment that is directed by genetic testing works in patients with solid tumors, lymphomas, or multiple myelomas that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and does not respond to treatment (refractory). Patients must have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVE: I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma. SECONDARY OBJECTIVES: I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma. II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms. IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens. OUTLINE: STEP 0 (Screening): Patients undergo biopsy along with molecular characterization of the biopsy material for specific, pre-defined mutations, amplifications, or translocations of interest via tumor sequencing and immunohistochemistry. Consenting patients also undergo collection of blood samples for research purposes. STEPS 1, 3, 5, 7 (Treatment): Patients are assigned to 1 of 38 treatment subprotocols based on molecularly-defined subgroup. (See Arms Section) STEPS 2, 4, 6 (Screening): Patients experiencing disease progression on the prior Step treatment or who could not tolerate the assigned treatment undergo review of their previous biopsy results to determine if another treatment is available or undergo another biopsy. Patients may have a maximum of 2 screening biopsies and 2 treatments per biopsy. STEP 8 (Optional Research): Consenting patients undergo end-of-treatment biopsy and collection of blood samples for research purposes. Additionally, patients may undergo a computed tomography (CT) scan, magnetic resonance imaging, and/or radionuclide imaging throughout the trial. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.

Intervention public domain (ClinicalTrials.gov)

Drug: Adavosertib. Given PO

Intervention public domain (ClinicalTrials.gov)

Drug: Afatinib. Given PO

Intervention public domain (ClinicalTrials.gov)

Drug: Afatinib Dimaleate. Given PO

Intervention public domain (ClinicalTrials.gov)

Drug: Binimetinib. Given PO

Intervention public domain (ClinicalTrials.gov)

Procedure: Biopsy Procedure. Undergo tumor biopsy

Intervention public domain (ClinicalTrials.gov)

Procedure: Biospecimen Collection. Undergo collection of blood samples

Intervention public domain (ClinicalTrials.gov)

Drug: Capivasertib. Given PO

Intervention public domain (ClinicalTrials.gov)

Procedure: Computed Tomography. Undergo computed tomography (CT)

Arm public domain (ClinicalTrials.gov)

Subprotocol A (EGFR activating mutation) (experimental): Patients with EGFR activating mutation receive afatinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients may also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study.

Arm public domain (ClinicalTrials.gov)

Subprotocol B (HER2 activating mutation) (experimental): Patients with HER2 activating mutation receive afatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Arm public domain (ClinicalTrials.gov)

Subprotocol C1 (MET amplification) (experimental): Patients with MET amplification receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation and collection of blood samples throughout the study. Patients may undergo biopsy at screening, on study, and/or at end of treatment.

Arm public domain (ClinicalTrials.gov)

Subprotocol C2 (MET exon 14 deletion/mutation) (experimental): Patients with MET exon 14 deletion or other mutations that disrupt exon 14 receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy on study and undergo radiologic evaluation and blood sample collection throughout the study.

Arm public domain (ClinicalTrials.gov)

Subprotocol E (EGFR T790M or rare activating mutation) (experimental): Patients with EGFR T790M or rare activating mutation receive osimertinib (AZD9291) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO or multigated acquisition scan (MUGA) during screening, and biopsy and collection of blood samples on trial and at end of treatment.

Arm public domain (ClinicalTrials.gov)

Subprotocol F (ALK translocation) (experimental): Patients with ALK translocation receive crizotinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary outcome public domain (ClinicalTrials.gov)

Objective response rate (ORR). ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 90% two-sided confidence interval is calculated for ORR. For the purposes of this study, patients should be re-evaluated for response: * For treatments given in 21 day (3 week) cycles: every 3 cycles (9 weeks) for the first 33 cycles, and every 4 cycles thereafter (12 weeks) * For treatments given in 28 day (4 week) cycles: every 2 cycles (8 weeks) for the first 26 cycles, and every three cycles thereafter (12 weeks) * For treatments given in 42 day (6 week) cycles: every 2 cycles (12 weeks) Time frame: Up to 3 years.

Secondary outcome public domain (ClinicalTrials.gov)

Overall survival (OS). Time frame: From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years.

Secondary outcome public domain (ClinicalTrials.gov)

6-month progression free survival (PFS) rate. Time frame: From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months.

Secondary outcome public domain (ClinicalTrials.gov)

Progression free survival. Time frame: From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * ELIGIBILITY CRITERIA FOR SCREENING BIOPSY (STEP 0) * Patients must be \>= 18 years of age. Because no dosing or adverse event data are currently available on the use of study investigational agents in patients \< 18 years of age, children are excluded from this study * Patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to registration; patients that are pregnant or breast feeding are excluded; a patient of childbearing potential is anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: * Has achieved menarche at some point * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal 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 prior to study entry, for the duration of study participation, and for 4 months after completion of study; should a patient or partner of the patient become pregnant or suspect a pregnancy while participating in this study, the treating physician should be informed immediately * Patients must have histologically documented solid tumors or histologically confirmed diagnosis of lymphoma or multiple myeloma requiring therapy and meet one of the following criteria: * Patients must have progressed following at least one line of standard systemic therapy and there must not be other approval/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolong overall survival due to medical issues will be eligible, if other eligibility criteria are met; if the patient is currently receiving therapy, the clinician must have assessed that the current therapy is no longer benefitting the patient prior to enrolling on MATCH, regardless of whether it is considered standard OR * Patients for whose disease no standard treatment exists that has been shown to prolong overall survival * NOTE: No other prior malignancy is allowed except for the following: * Adequately treated basal cell or squamous cell skin cancer * In situ cervical cancer * Adequately treated stage I or II cancer from …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 6452 participants (estimated).