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Testing Binimetinib as a Potential Targeted Treatment in Cancers With NRAS Genetic Changes (MATCH-Subprotocol Z1A)

Primary Purpose

Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Binimetinib
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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 NRAS mutation in codon 12, 13, 61 as determined via the MATCH Master Protocol
  • Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically significant abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
  • Creatinine =< 1.5 mg/dL, or calculated creatinine clearance (determined as per Cockcroft-Gault) >= 50mL/min
  • Patients must have adequate cardiac function:

    • Left ventricular ejection fraction (LVEF) >= 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram,
    • QTc interval =< 480 ms

Exclusion Criteria:

  • Patients must not have known hypersensitivity to binimetinib or compounds of similar chemical or biologic composition
  • Patients with melanoma are excluded
  • Patients must not have any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases

    • NOTE: Patients treated with stereotactic radiotherapy or surgery are eligible if the patient remained without evidence of CNS disease progression >= 3 months. Patients must be off corticosteroid therapy for >= 3 weeks
  • Patients must not have a history or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
  • Patients must not have a history of retinal degenerative disease
  • Patients must not have a history of Gilbert's syndrome
  • Patients must not have uncontrolled arterial hypertension despite medical treatment
  • Patients must not have active hepatitis B, and/or active hepatitis C infection
  • Patients must not have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
  • Patients must not have impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
  • Patients who have received prior MEK inhibitors are excluded

Sites / Locations

  • ECOG-ACRIN Cancer Research Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (binimetinib)

Arm Description

Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR)
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 criteria for solid tumors, 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

6-Month Progression-free Survival (PFS) Rate
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. 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. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
Progression Free Survival (PFS)
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. 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. Median PFS was estimated using the Kaplan-Meier method.

Full Information

First Posted
June 18, 2020
Last Updated
June 6, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04439344
Brief Title
Testing Binimetinib as a Potential Targeted Treatment in Cancers With NRAS Genetic Changes (MATCH-Subprotocol Z1A)
Official Title
MATCH Treatment Subprotocol Z1A: Binimetinib in Patients With Tumors (Other Than Melanoma) With NRAS Mutations
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 31, 2016 (Actual)
Primary Completion Date
May 3, 2019 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II MATCH treatment trial investigates the good and bad effects of binimetinib in patients whose cancer has a genetic change called NRAS mutation. Binimetinib blocks proteins called MEK1 and MEK2, which may be needed for cancer cell growth when an NRAS mutation is present. Researchers hope to learn if binimetinib will shrink this type of cancer or stop its growth.
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 binimetinib orally (PO) twice daily (BID) 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (binimetinib)
Arm Type
Experimental
Arm Description
Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Binimetinib
Other Intervention Name(s)
ARRY-162, ARRY-438162, MEK162, Mektovi
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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 criteria for solid tumors, 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.
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
Secondary Outcome Measure Information:
Title
6-Month Progression-free Survival (PFS) Rate
Description
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. 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. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
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, from which 6-month PFS is determined
Title
Progression Free Survival (PFS)
Description
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. 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. Median PFS was estimated using the Kaplan-Meier method.
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol Patients must have NRAS mutation in codon 12, 13, 61 as determined via the MATCH Master Protocol Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically significant abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block) Creatinine =< 1.5 mg/dL, or calculated creatinine clearance (determined as per Cockcroft-Gault) >= 50mL/min Patients must have adequate cardiac function: Left ventricular ejection fraction (LVEF) >= 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram, QTc interval =< 480 ms Exclusion Criteria: Patients must not have known hypersensitivity to binimetinib or compounds of similar chemical or biologic composition Patients with melanoma are excluded Patients must not have any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases NOTE: Patients treated with stereotactic radiotherapy or surgery are eligible if the patient remained without evidence of CNS disease progression >= 3 months. Patients must be off corticosteroid therapy for >= 3 weeks Patients must not have a history or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes) Patients must not have a history of retinal degenerative disease Patients must not have a history of Gilbert's syndrome Patients must not have uncontrolled arterial hypertension despite medical treatment Patients must not have active hepatitis B, and/or active hepatitis C infection Patients must not have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) Patients must not have impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) Patients who have received prior MEK inhibitors are excluded
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James M Cleary
Organizational Affiliation
ECOG-ACRIN Cancer Research Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
ECOG-ACRIN Cancer Research Group
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19103
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Testing Binimetinib as a Potential Targeted Treatment in Cancers With NRAS Genetic Changes (MATCH-Subprotocol Z1A)

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