13 Participants Needed

Defactinib + VS-6766 for Uveal Melanoma

TS
RS
Overseen ByRino Seedor, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This trial studies the effect of combining two drugs, defactinib and VS-6766, in patients with metastatic uveal melanoma. These drugs aim to block signals in cancer cells that make them grow and spread, potentially slowing down or stopping the cancer. Everolimus has been studied in combination with other drugs for its potential to inhibit cancer cell growth in various types of tumors, including uveal melanoma.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that patients exposed to strong CYP3A4 and CYP2C9 inhibitors within 7 days prior to the first dose are excluded. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug Defactinib + VS-6766 for Uveal Melanoma?

Research shows that targeting the Ras/Raf/MEK/ERK pathway, which is active in uveal melanoma, with MEK inhibitors like selumetinib has shown antitumor effects and improved outcomes in pre-clinical models and trials. This suggests that similar drugs, like VS-6766, may also be effective.12345

What makes the drug Defactinib + VS-6766 unique for uveal melanoma?

Defactinib + VS-6766 is unique because it combines a FAK inhibitor (Defactinib) with a Raf/MEK inhibitor (VS-6766), targeting specific pathways involved in cancer cell growth and survival, which are not addressed by standard treatments for uveal melanoma.12678

Research Team

RS

Rino Seedor, MD

Principal Investigator

Thomas Jefferson University

Eligibility Criteria

Adults with metastatic uveal melanoma, good heart function, and no severe systemic diseases. They must not be pregnant or breastfeeding and agree to use effective contraception. Participants need stable vital signs and blood counts within specific ranges, can't have had recent major surgery or certain treatments, and must not have active infections like hepatitis or HIV.

Inclusion Criteria

My white blood cell count is high enough for the trial.
I have signed and understand the consent form and can follow the treatment plan.
I am fully active or can carry out light work.
See 18 more

Exclusion Criteria

Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial
I cannot take pills by mouth or have issues absorbing them due to stomach surgery or active bowel inflammation.
I haven't had major surgery in the last 4 weeks or minor surgery in the last 2 weeks.
See 17 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive defactinib orally twice daily and VS-6766 twice a week for 3 weeks in every cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Up to 2 years
Regular visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months until death or up to 2 years after the last patient is enrolled.

Up to 2 years
Every 3 months

Treatment Details

Interventions

  • Defactinib Hydrochloride
  • Raf/MEK Inhibitor VS-6766
Trial Overview The trial is testing a combination of two drugs: Defactinib Hydrochloride and Raf/MEK Inhibitor VS-6766 on patients with metastatic uveal melanoma. It aims to see if blocking cell signaling pathways slows down cancer growth or shrinks tumors.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (defactinib, VS-6766)Experimental Treatment3 Interventions
Patients receive defactinib PO BID and VS-6766 PO BIW (Monday and Thursday or Tuesday and Friday) for 3 weeks in every cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials
475
Recruited
189,000+

Verastem, Inc.

Industry Sponsor

Trials
42
Recruited
2,800+

Findings from Research

The SUMIT trial is a phase III study involving 128 patients with metastatic uveal melanoma, testing the combination of selumetinib (a MEK1/2 inhibitor) and dacarbazine, aiming to improve progression-free survival compared to dacarbazine alone.
Previous studies indicated that selumetinib showed antitumor effects in pre-clinical models and improved outcomes in a phase II trial, making this combination a promising approach for patients who have not received prior systemic therapy.
Study design and rationale for a randomised, placebo-controlled, double-blind study to assess the efficacy of selumetinib (AZD6244; ARRY-142886) in combination with dacarbazine in patients with metastatic uveal melanoma (SUMIT).Carvajal, RD., Schwartz, GK., Mann, H., et al.[2018]
In the Treat20 Plus study, a precision oncology approach was successfully implemented for 45 patients with metastatic uveal melanoma, with 60% receiving therapies matched to their specific molecular profiles, demonstrating the feasibility of this strategy in clinical practice.
The matched therapies led to a clinical benefit in 56% of patients, with a median overall survival of 13.9 months, highlighting the potential effectiveness of personalized treatment based on tumor mutational burden.
Biomarker-driven therapies for metastatic uveal melanoma: A prospective precision oncology feasibility study.Leyvraz, S., Konietschke, F., Peuker, C., et al.[2022]
The study evaluated the effectiveness of the MEK inhibitor selumetinib in combination with various drugs for treating metastatic uveal melanoma, finding that combining selumetinib with the chemotherapy drug DTIC did not enhance its antitumor effects, aligning with previous clinical trial results.
However, combinations of selumetinib with ERK and mTORC1/2 inhibitors showed promising efficacy in patient-derived xenograft models, suggesting these combinations may be more effective treatment strategies for this aggressive cancer.
Selumetinib-based therapy in uveal melanoma patient-derived xenografts.Decaudin, D., El Botty, R., Diallo, B., et al.[2019]

References

The multi-kinase inhibitor afatinib serves as a novel candidate for the treatment of human uveal melanoma. [2022]
Study design and rationale for a randomised, placebo-controlled, double-blind study to assess the efficacy of selumetinib (AZD6244; ARRY-142886) in combination with dacarbazine in patients with metastatic uveal melanoma (SUMIT). [2018]
Biomarker-driven therapies for metastatic uveal melanoma: A prospective precision oncology feasibility study. [2022]
Uveal Melanoma: 5-Year Update on Incidence, Treatment, and Survival (SEER 1973-2013). [2022]
Selumetinib-based therapy in uveal melanoma patient-derived xenografts. [2019]
New therapeutic agents in uveal melanoma. [2012]
The role of c-kit and imatinib mesylate in uveal melanoma. [2020]
Globe Salvage and Vision Preservation by Neoadjuvant Darovasertib and Crizotinib in Uveal Melanoma. [2023]