Testing Trametinib as a Potential Targeted Treatment in Cancers With BRAF Genetic Changes (MATCH-Subprotocol R)

March 6, 2024 updated by: National Cancer Institute (NCI)

MATCH Treatment Subprotocol R: Phase II Study of Trametinib in Patients With BRAF Fusions, or With NonV600E, Non-V600K BRAF Mutations

This phase II MATCH treatment trial identifies the effects of trametinib in patients with cancer having genetic changes called BRAF mutations and fusions. Trametinib may block proteins called MEK1 and MEK2, which may be needed for growth of cancer cells that express BRAF mutations. Researchers hope to learn if giving trametinib will shrink this type of cancer or stop its growth.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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:

Patients receive trametinib dimethyl sulfoxide (trametinib) 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.

After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19103
        • ECOG-ACRIN Cancer Research Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
  • Patients must have a BRAF non-V600 mutation or BRAF fusion, or another aberration, as identified via the MATCH Master Protocol

  • Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have NONE of the following cardiac criteria:

    • Clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
    • Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy
  • Patients must have an echocardiogram (ECHO) or a nuclear study (multigated acquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be > 50% for the patient to be eligible
  • Patients who previously received monoclonal antibody therapy (e.g. ipilimumab, nivolumab, pembrolizumab and others) must have stopped the prior therapy for 8 or more weeks before starting on trametinib

Exclusion Criteria:

  • Patients with a history of interstitial lung disease or pneumonitis are excluded
  • Patients must not have known hypersensitivity to trametinib or compounds of similar chemical or biologic composition or to dimethyl sulfoxide (DMSO)
  • Patients must not have a history or current evidence/risk of retinal vein occlusion (RVO). An eye exam is required at baseline
  • Patients who previously received MEK inhibitors (including, but not limited to, trametinib, binimetinib, cobimetinib, selumetinib, RO4987655 (CH4987655), GDC-0623 and pimasertib) will be excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (trametinib)
Patients receive trametinib dimethyl sulfoxide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Trametinib Dimethyl Sulfoxide
Given PO
Other Names:
  • Mekinist
  • Meqsel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: assessed at baseline, then every 2 cycles until disease progression, up to 3 years post registration
Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the 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. The 90% two-sided binomial exact confidence interval was calculated for ORR.
assessed at baseline, then every 2 cycles until disease progression, up to 3 years post registration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
6-month Progression-free Survival (PFS) Rate
Time Frame: assessed at baseline, then every 2 cycles until disease progression, up to 3 years post registration
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. The 6-month PFS rate was estimated using the Kaplan-Meier method which can provide a point estimate for any specific time point. Disease progression was evaluated using the 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.
assessed at baseline, then every 2 cycles until disease progression, up to 3 years post registration
Progression-free Survival
Time Frame: assessed at baseline, then every 2 cycles until disease progression, up to 3 years post registration
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the 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.
assessed at baseline, then every 2 cycles until disease progression, up to 3 years post registration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Douglas B Johnson, ECOG-ACRIN Cancer Research Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 12, 2015

Primary Completion (Actual)

March 18, 2019

Study Completion (Estimated)

March 5, 2025

Study Registration Dates

First Submitted

June 18, 2020

First Submitted That Met QC Criteria

June 18, 2020

First Posted (Actual)

June 19, 2020

Study Record Updates

Last Update Posted (Actual)

April 2, 2024

Last Update Submitted That Met QC Criteria

March 6, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2020-03272 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180820 (U.S. NIH Grant/Contract)
  • U24CA196172 (U.S. NIH Grant/Contract)
  • EAY131-R (Other Identifier: CTEP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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