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Testing VS-6063 (Defactinib) as a Potential Targeted Treatment in Cancers With NF2 Genetic Changes (MATCH-Subprotocol U)

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

Defactinib Hydrochloride

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 a tumor that harbors an inactivating mutation in NF2
Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
Patients with known left ventricular dysfunction must have 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 left ventricular ejection fraction (LVEF) < 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 with history of hypertension should be adequately controlled (blood pressure [BP] < 140/90) with appropriate anti-hypertensive therapy or diet

Exclusion Criteria:

Patients must not have known hypersensitivity to VS-6063 (defactinib) or compounds of similar chemical or biologic composition
Patients must not have a history of upper gastrointestinal (GI) bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug
Patients must not have known history of Gilbert's syndrome
Patient must not have a known history of stroke or cerebrovascular accident within 6 months prior to the first dose of VS-6063 (defactinib)
Patients must not have prior treatment with a FAK inhibitor (e.g., VS-6063 [defactinib] or GSK2256098) and must not be participating or have participated in the COMMAND trial of maintenance therapy of VS-6063 (defactinib) versus (vs.) placebo, for mesothelioma
Patients must not be using drugs or foods that are known potent CYP3A4 or CYP2C9 inhibitors or inducers. Substrates of CYP3A4, 2C9, UGT1A1, P-gp, OATP1B1, and OATP1B3 should be used with caution

Sites / Locations

ECOG-ACRIN Cancer Research Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (defactinib)

Arm Description

Patients receive defactinib 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, 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)

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)

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.

Full Information

NCT ID

NCT04439331

First Posted

June 18, 2020

Last Updated

September 12, 2023

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04439331

Brief Title

Testing VS-6063 (Defactinib) as a Potential Targeted Treatment in Cancers With NF2 Genetic Changes (MATCH-Subprotocol U)

Official Title

MATCH Treatment Subprotocol U: VS-6063 (Defactinib) in Patients With Tumors With NF2 Loss

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 12, 2015 (Actual)

Primary Completion Date

May 31, 2024 (Anticipated)

Study Completion Date

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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 identifies the effects of VS-6063 (defactinib) in patients whose cancer has a genetic change called NF2 mutation. Defactinib may block a protein called FAK, which may be needed for cancer cell growth when NF2 mutations are present. Researchers hope to learn if defactinib 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 defactinib hydrochloride (defactinib) 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

35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment (defactinib)

Arm Type

Experimental

Arm Description

Patients receive defactinib 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)

Defactinib Hydrochloride

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Objective response rate (ORR)

Description

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

Overall survival (OS)

Description

Time Frame

Assessed every 3 months for =< 2 years and every 6 months for year 3

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. PFS will be 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

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 a tumor that harbors an inactivating mutation in NF2 Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block) Patients with known left ventricular dysfunction must have 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 left ventricular ejection fraction (LVEF) < 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 with history of hypertension should be adequately controlled (blood pressure [BP] < 140/90) with appropriate anti-hypertensive therapy or diet Exclusion Criteria: Patients must not have known hypersensitivity to VS-6063 (defactinib) or compounds of similar chemical or biologic composition Patients must not have a history of upper gastrointestinal (GI) bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug Patients must not have known history of Gilbert's syndrome Patient must not have a known history of stroke or cerebrovascular accident within 6 months prior to the first dose of VS-6063 (defactinib) Patients must not have prior treatment with a FAK inhibitor (e.g., VS-6063 [defactinib] or GSK2256098) and must not be participating or have participated in the COMMAND trial of maintenance therapy of VS-6063 (defactinib) versus (vs.) placebo, for mesothelioma Patients must not be using drugs or foods that are known potent CYP3A4 or CYP2C9 inhibitors or inducers. Substrates of CYP3A4, 2C9, UGT1A1, P-gp, OATP1B1, and OATP1B3 should be used with caution

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David M Jackman

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 VS-6063 (Defactinib) as a Potential Targeted Treatment in Cancers With NF2 Genetic Changes (MATCH-Subprotocol U)

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