What side effects are associated with this type of intervention?

Common cancer treatments, including those similar to Defactinib (FAK inhibition), often have a range of side effects. For instance, treatments like masitinib combined with gemcitabine can lead to increased toxicity, though these side effects are generally manageable. Adverse events for other targeted therapies, such as afatinib, include diarrhea and neutropenia, while fruquintinib is associated with high rates of grades 3 and 4 treatment-emergent adverse events, including serious adverse events requiring hospitalization. Additionally, combination therapies involving BRAF/MEK inhibitors can induce severe side effects, though they are typically manageable and reversible. Overall, while targeted cancer therapies can be effective, they often come with significant side effects that need to be carefully managed.

What prior FDA approvals exist?

Defactinib is a FAK inhibitor being studied for its potential in treating cancers with NF2 mutations. While there are no specific FDA-approved FAK inhibitors for cancer treatment, several other targeted therapies have been approved. These include tyrosine kinase inhibitors (TKIs) like imatinib for chronic myeloid leukemia and erlotinib for non-small cell lung cancer, which target specific molecular pathways involved in cancer growth. Additionally, monoclonal antibodies such as trastuzumab for HER2-positive breast cancer and immune checkpoint inhibitors like pembrolizumab for various cancers with high tumor mutational burden have also been approved.

What other types of research exist?

Promising alternatives to Defactinib for cancer treatment include: 1) Vemurafenib plus Rituximab for BRAF-mutated cancers, 2) Afatinib followed by Osimertinib for EGFR mutation-positive NSCLC, 3) Trabectedin for advanced leiomyosarcoma and liposarcoma, and 4) CDK4 inhibitors like Abemaciclib for dedifferentiated liposarcoma. These therapies have shown efficacy in clinical trials and represent viable options for cancer patients.

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FAK Inhibitor

Defactinib for Cancer with NF2 Mutations

Phase 2

Waitlist Available

Led By David M Jackman

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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)

Must not have

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 have known history of Gilbert's syndrome

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 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

Awards & highlights

Summary

This trial tests defactinib, a drug that blocks a protein called FAK, in patients with advanced cancers that have an NF2 mutation. Researchers aim to see if the drug can shrink the cancer or stop it from growing.

Who is the study for?

This trial is for cancer patients with a specific genetic change called NF2 mutation. They must have passed previous MATCH Protocol criteria, have no serious heart issues or uncontrolled high blood pressure, and not be allergic to defactinib. People with recent GI bleeding, Gilbert's syndrome, stroke history within 6 months, prior FAK inhibitor treatment like defactinib or certain drug/food interactions are excluded.

What is being tested?

The trial tests VS-6063 (defactinib hydrochloride), which may block the FAK protein that supports cancer cell growth in patients with NF2 mutations. The goal is to see if it can shrink these cancers or halt their progression.

What are the potential side effects?

Potential side effects of defactinib include but are not limited to: risks associated with heart rhythm changes due to its interaction with cardiac function and possible gastrointestinal complications such as bleeding or ulceration.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My tumor has an NF2 mutation.

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My recent ECG showed no significant heart issues.

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My heart's pumping ability is normal according to recent tests.

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My high blood pressure is under control.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have never been treated with FAK inhibitors or participated in the COMMAND trial.

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I do not have a history of Gilbert's syndrome.

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I am not allergic to VS-6063 (defactinib) or similar drugs.

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I haven't had any upper GI bleeding, ulcers, or perforations in the last year.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 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

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~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

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective response rate (ORR)

Secondary study objectives

Overall survival (OS)

Progression free survival (PFS)

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (defactinib)Experimental Treatment1 Intervention

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

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Targeted therapies, like Defactinib, work by inhibiting specific molecules involved in cancer cell growth and survival. Defactinib targets Focal Adhesion Kinase (FAK), a protein that helps cancer cells spread and survive. By blocking FAK, Defactinib aims to reduce tumor growth and metastasis. Other common treatments include chemotherapy, which kills rapidly dividing cells; immunotherapy, which boosts the immune system to attack cancer cells; and radiation therapy, which uses high-energy particles to destroy cancer cells. Understanding these mechanisms helps patients and doctors choose the most effective treatment based on the cancer's specific characteristics, potentially improving outcomes and minimizing side effects.

Therapeutic approaches for relapsed/refractory adult acute lymphoblastic leukemia (ALL), a review on monoclonal antibodies and targeted therapies.Network meta-analyses for EGFR mutation-positive non-small-cell lung cancer: systematic review and overview of methods and shortcomings.New and emerging combination therapies for esophageal cancer.