Defactinib for Cancer with NF2 Mutations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Stroke, GI bleeding, Gilbert's, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

35 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you should avoid drugs or foods that strongly affect certain liver enzymes (CYP3A4 or CYP2C9). It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Defactinib Hydrochloride for cancer with NF2 mutations?

Defactinib, also known as VS-6063, has been studied in patients with advanced solid tumors, showing some clinical activity and safety in early-phase trials. While these studies do not directly address NF2 mutations, they suggest potential effectiveness in treating solid tumors, which may be relevant for cancers with NF2 mutations. ^{1 2 3 4 5}

What makes the drug Defactinib Hydrochloride unique for treating cancer with NF2 mutations?

Defactinib Hydrochloride is unique because it specifically targets cancer with NF2 mutations, which are not commonly addressed by standard treatments. This drug may offer a novel approach by focusing on the underlying genetic mutations, potentially providing a more tailored and effective treatment option for patients with this specific type of cancer. ^{6 7 8 9 10}

Research Team

David M Jackman

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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.

Inclusion Criteria

Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol

My tumor has an NF2 mutation.

My recent ECG showed no significant heart issues.

Exclusion Criteria

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

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

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Treatment

Participants receive defactinib orally 400 mg twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Up to 3 years

Treatment Details

Interventions

• Defactinib Hydrochloride

Trial Overview 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.

Participant Groups

Group I: Treatment (defactinib) Experimental Treatment 1 Intervention

Patients receive defactinib PO 400 mg BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

A phase I study of VS-6063, a second-generation focal adhesion kinase inhibitor, in patients with advanced solid tumors. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Neurotrophic tyrosine kinase inhibitors: A review of implications for patients, clinicians and healthcare services. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

ALK kinase domain mutations in primary anaplastic large cell lymphoma: consequences on NPM-ALK activity and sensitivity to tyrosine kinase inhibitors. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

NTRK fusion events and targeted treatment of advanced radioiodine refractory thyroid cancer. [2023]

6. Canada pubmed.ncbi.nlm.nih.gov

DPYD Genotyping in Patients Who Have Planned Cancer Treatment With Fluoropyrimidines: A Health Technology Assessment. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Fluoropyrimidine chemotherapy: recommendations for DPYD genotyping and therapeutic drug monitoring of the Swiss Group of Pharmacogenomics and Personalised Therapy. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

All You Need to Know About DPYD Genetic Testing for Patients Treated With Fluorouracil and Capecitabine: A Practitioner-Friendly Guide. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Assessment of the Clinical Utility of Pretreatment DPYD Testing for Patients Receiving Fluoropyrimidine Chemotherapy. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines. [2022]