Testing VS-6063 (Defactinib) as a Potential Targeted Treatment in Cancers With NF2 Genetic Changes (MATCH-Subprotocol U)
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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:
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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.
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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.
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (defactinib) Patients receive defactinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Drug: Defactinib Hydrochloride
Given PO
Other Names:
|
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
Inclusion Criteria:
-
Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
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Patients must have a tumor that harbors an inactivating mutation in NF2
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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)
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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
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Patients with history of hypertension should be adequately controlled (blood pressure [BP] < 140/90) with appropriate anti-hypertensive therapy or diet
Exclusion Criteria:
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Patients must not have known hypersensitivity to VS-6063 (defactinib) or compounds of similar chemical or biologic composition
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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
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Patients must not have known history of Gilbert's syndrome
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Patient must not have a known history of stroke or cerebrovascular accident within 6 months prior to the first dose of VS-6063 (defactinib)
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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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ECOG-ACRIN Cancer Research Group | Philadelphia | Pennsylvania | United States | 19103 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: David M Jackman, ECOG-ACRIN Cancer Research Group
Study Documents (Full-Text)
More Information
Publications
None provided.- NCI-2020-03368
- NCI-2020-03368
- EAY131-U
- EAY131-U
- U10CA180820
- U24CA196172