Title
Molecular Analysis for Combination Therapy Choice (ComboMATCH)

Description
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.

Objective
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).

Treatment This initiative will evaluate patients with locally advanced or advanced histologically documented solid tumors in two main groups. First, patients who have progressed on at least one standard systemic therapy. Second, patients for whom no standard therapy exists.

Key Eligibility 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

Applicable Disease Sites
Anal; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

Participating Institutions
American Family Children's Hospital (AFCH); Mercy Health Systems, Janesville ; UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital