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Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial

ConditionsAdvanced Malignant Solid NeoplasmAnatomic Stage III Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Locally Advanced Malignant Solid NeoplasmMalignant Female Reproductive System NeoplasmMetastatic HER2-Negative Breast CarcinomaMetastatic Malignant Solid NeoplasmRecurrent Endometrial CarcinomaRecurrent Fallopian Tube CarcinomaRecurrent Malignant Female Reproductive System NeoplasmRecurrent Malignant Solid NeoplasmRecurrent Ovarian CarcinomaRecurrent Primary Peritoneal CarcinomaUnresectable HER2-Negative Breast CarcinomaUnresectable Malignant Solid Neoplasm
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorNational Cancer Institute (NCI)

About this 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

Disqualifiers

None

Trial design

Design model

Single group

Treatments tested in this trial

  • Alpelisib

    Drug

    Given PO

  • Binimetinib

    Drug

    Given PO

  • Biopsy Procedure

    Procedure/Surgery

    Undergo biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood collection

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow aspiration

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

  • Bone Scan

    Procedure/Surgery

    Undergo bone scan

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Echocardiography Test

    Procedure/Surgery

    Undergo ECHO

  • Fluorouracil

    Drug

    Given IV

  • Fulvestrant

    Drug

    Given IM

  • Ipatasertib

    Drug

    Given PO

  • Leucovorin

    Drug

    Given IV

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA

  • Mutation Carrier Screening

    Procedure/Surgery

    Undergo tumor mutational screening

  • Neratinib Maleate

    Drug

    Given PO

  • Nilotinib Hydrochloride Monohydrate

    Drug

    Given PO

  • Olaparib

    Drug

    Given PO

  • Oxaliplatin

    Drug

    Given IV

  • Paclitaxel

    Drug

    Given PO or IV

  • Palbociclib

    Drug

    Given PO

  • Panitumumab

    Biological/Vaccine

    Given IV

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET

  • Selumetinib Sulfate

    Drug

    Given PO

  • Sotorasib

    Drug

    Given PO

Treatment groups

2,900 Participants
are divided into 20 treatment groups

20

Treatment groups

See each treatment group below.

Group A: EAY191-A2 (Cohort 1, Arm A)Experimental treatment 8 interventions
Group B: EAY191-A2 (Cohort 2, Arm B)Experimental treatment 8 interventions
Group C: EAY191-A2 (Cohort 2, Arm C)Experimental treatment 7 interventions
Group D: EAY191-A2 (Cohort 3, Arm D)Experimental treatment 7 interventions
Group E: EAY191-A3 Combo Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)Experimental treatment 6 interventions
Group F: EAY191-A3 Monotherapy Cohort 1 (binimetinib)Experimental treatment 6 interventions
Group G: EAY191-A6 Arm I (RAS/RAF/MEK/ERK mutations)Experimental treatment 11 interventions
Group H: EAY191-A6 Arm II (RAS/RAF/MEK/ERK mutations)Experimental treatment 11 interventions
Group I: EAY191-E4 (taxane therapy)Experimental treatment 6 interventions
Group J: EAY191-E5 Cohort I Arm A (sotorasib, panitumumab)Experimental treatment 6 interventions
Group K: EAY191-E5 Cohort I Arm B (sotorasib)Active comparator 5 interventions
Group L: EAY191-E5 Cohort II (sotorasib)Experimental treatment 6 interventions
Group M: EAY191-N2 Cohort I (Arm I) (NF1 mutations)Experimental treatment 9 interventions
Group N: EAY191-N2 Cohort I (Arm II) (NF1 mutations)Experimental treatment 8 interventions
Group O: EAY191-N2 Cohort II (NF1 mutations)Experimental treatment 9 interventions
Group P: EAY191-N4 Arm I (RAS pathway mutations)Experimental treatment 10 interventions
Group Q: EAY191-N4 Arm II (RAS pathway mutations)Active comparator 9 interventions
Group R: EAY191-N5 Arm I (neratinib maleate)Active comparator 7 interventions
Group S: EAY191-N5 Arm II (neratinib maleate,palbociclib)Experimental treatment 8 interventions
Group T: EAY191-S3 (activating AKT mutation)Experimental treatment 6 interventions

Trial outcomes

Primary outcomes

1

Accrual of patients to ComboMATCH treatment trials

Will be estimated over time and considered in relationship to changes in treatment trial cohort status (activations, suspensions, terminations).

Time frame
Up to 8 years
2

Assignment of patients to ComboMATCH treatment trials

Will be estimated over time and considered in relationship to changes in treatment trial cohort status (activations, suspensions, terminations).

Time frame
Up to 8 years
3

Enrollment rates to ComboMATCH treatment trials

Will be estimated over time and considered in relationship to changes in treatment trial cohort status (activations, suspensions, terminations).

Time frame
Up to 8 years

Secondary outcomes

1

Rate of positive outcomes within the treatment trial defined cohorts

For each cohort in each treatment trial there is a defined primary efficacy endpoint (usually progression free survival \[PFS\] or overall response rate) and defined primary analysis for evaluating the primary endpoint. As cohorts are completed, whether they meet the criteria for a positive primary outcome will be determined. Positive treatment cohort outcome (on primary endpoint) will be analyzed as a binary random variable. The raw proportion of treatment cohorts with positive outcomes and an exact binomial confidence interval will be computed. If there are a sufficient number of treatment cohorts, logistic regression analysis will be performed examining the relationship of treatment cohort characteristics with successful outcomes. The goal is to achieve a rate of at least 30% with positive outcomes, both overall and in the subset of treatment trials based on in vivo models.

Time frame
Up to 8 years

Other outcomes

1

Concordance between whole exome sequencing (WES) and results from the Designated Laboratory (DL)

Whole exome and other sequencing will be performed on mandatory tissue biopsies or, if no biopsy tissue is available, on submitted formalin-fixed paraffin-embedded tissue. These assays will be done in a clinical laboratory (e.g., Clinical Laboratory Improvement Act-compliant); but results will not be returned to the clinical site. Results will be used to compare with the DL assay results. This comparison will be required to conduct an important secondary analysis of the primary endpoint in each cohort in each treatment trial, restricting to those cases that are concordant between WES and the result from the DL that was the basis for enrollment (integrated).

Time frame
Up to 8 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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