Testing Trametinib as a Potential Targeted Treatment in Cancers With NF1 Genetic Changes (MATCH-Subprotocol S1)

NCT04439318 | Active Not Recruiting Phase 2 Results DMC

• 4 other identifiers: NCI-2020-03343EAY131-S1U10CA180820U24CA196172
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II MATCH treatment trial identifies the effects of trametinib in patients whose cancer has a has a genetic change called NF1 mutation. Trametinib blocks proteins called MEK1 and MEK2, which may be needed for cancer cell growth when an NF1 mutation is present. Researchers hope to learn if trametinib will shrink this type of cancer or stop its growth.

Conditions

Advanced Lymphoma; Hematopoietic and Lymphoid Cell Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Multiple Myeloma; Advanced Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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. Please refer to the protocol for the detailed definitions of response criteria. The 90% two-sided binomial exact confidence interval was calculated for ORR.

  Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Secondary Outcomes (2)

• 6-month Progression-free Survival (PFS) Rate

  Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined

• Progression Free Survival (PFS)

  Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Study Arms (1)

Treatment (trametinib)

EXPERIMENTAL

Patients receive trametinib dimethyl sulfoxide PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Trametinib Dimethyl Sulfoxide

Interventions

Trametinib Dimethyl Sulfoxide DRUG

Given PO

Also known as: Mekinist, Meqsel, Spexotras

Treatment (trametinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
• Patients must have deleterious inactivating mutations of NF-1, or another aberration, as determined 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 (eg. ipilimumab, nivolumab, pembrolizumab and others) must have stopped the prior therapy for 8 or more weeks before starting on trametinib
• Patients with glioblastoma must have histologically or radiographically confirmed recurrent or progressive World Health Organization (WHO) grade 4 glioma (glioblastoma)
• NOTE: All baseline and post-baseline disease assessments must be performed using contrast-enhanced cranial magnetic resonance spectroscopy (MRI) or contrast-enhanced computed tomography (CT) for subjects who cannot have MRI performed

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Lymphoma; Multiple Myeloma

Interventions

trametinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Statistical Office

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• Jason J Luke

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 19, 2020
• Study Start: February 25, 2016
• Primary Completion: June 30, 2020
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 13, 2026
• Results First Posted: August 2, 2023

Record last verified: 2026-01

Locations

US (1)