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

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ClinicalTrials.gov Identifier: NCT04439357
Recruitment Status : Active, not recruiting
First Posted : June 19, 2020
Last Update Posted : July 26, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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:

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. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : February 25, 2016
Estimated Primary Completion Date : January 31, 2022


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 Name: Mekinist




Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 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 :
  1. Overall survival (OS) [ Time Frame: 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.

  2. Progression free survival (PFS) [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04439357


Locations
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United States, Pennsylvania
ECOG-ACRIN Cancer Research Group
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jason J Luke ECOG-ACRIN Cancer Research Group
  Study Documents (Full-Text)

Documents provided by National Cancer Institute (NCI):
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04439357    
Other Study ID Numbers: NCI-2020-03436
NCI-2020-03436 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EAY131-S2 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EAY131-S2 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
U24CA196172 ( U.S. NIH Grant/Contract )
First Posted: June 19, 2020    Key Record Dates
Last Update Posted: July 26, 2021
Last Verified: June 2021
Additional relevant MeSH terms:
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Lymphoma
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Trametinib
Dimethyl Sulfoxide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cryoprotective Agents
Protective Agents
Physiological Effects of Drugs
Free Radical Scavengers
Antioxidants