Testing Trametinib as a Potential Targeted Treatment in Cancers With GNAQ or GNA11 Genetic Changes (MATCH-Subprotocol S2)

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Active, not recruiting

CT.gov ID

NCT04439357

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

This phase II MATCH treatment trial identifies the effects of trametinib in patients whose cancer has genetic changes called GNAQ or GNA11 mutations. Trametinib may block proteins called MEK1 and MEK2, which may be needed for cancer cell growth when GNAQ or GNA11 mutations are present. Researchers hope to learn if trametinib will shrink this type of cancer or stop its growth.

Condition or Disease	Intervention/Treatment	Phase
Advanced Lymphoma Advanced Malignant Solid Neoplasm Hematopoietic and Lymphoid Cell Neoplasm Refractory Lymphoma Refractory Malignant Solid Neoplasm Refractory Plasma Cell Myeloma	Drug: Trametinib Dimethyl Sulfoxide	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

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:

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.
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.
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. 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 Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

MATCH Treatment Subprotocol S2: Phase II Study of Trametinib in Patients With Tumors With GNAQ or GNA11 Mutations

Actual Study Start Date :

Feb 25, 2016

Anticipated Primary Completion Date :

Oct 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (trametinib) 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 Given PO Other Names: Mekinist

Arm

Intervention/Treatment

Experimental: Treatment (trametinib)

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

Given PO

Other Names:

Mekinist

Outcome Measures

Primary Outcome Measures

Objective response rate (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]
ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate 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. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.

Secondary Outcome Measures

Overall survival (OS) [Assessed every 3 months for =< 2 years and every 6 months for year 3]
OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.
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]
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
Patients must have GNAQ or GNA11 mutations, 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 (e.g., 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 imaging (MRI) or contrast-enhanced computed tomography (CT) for subjects who cannot have MRI performed

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 prior treatment with other MEK inhibitors (including, but not limited to, trametinib, binimetinib, cobimetinib, selumetinib, RO4987655 [CH4987655], GDC-0623 and pimasertib) will be excluded
Patients with uveal melanoma are excluded