What side effects are associated with this type of intervention?

Common treatments for uveal melanoma that target overactive cell signaling pathways, such as MEK inhibitors and BRAF inhibitors, are associated with several ocular side effects. These include retinopathy, chorioretinopathy, retinal detachment, and blurred vision. Additionally, systemic chemotherapy agents can cause dry eye, chalazia, and other eyelid masses. Patients undergoing these treatments should be closely monitored by an ophthalmologist to manage and mitigate these side effects.

What prior FDA approvals exist?

FDA-approved treatments for uveal melanoma that involve blocking overactive cell signaling pathways include kinase inhibitors and other targeted therapies. While specific approvals for uveal melanoma are limited, drugs like selumetinib, a MEK inhibitor, have been studied for their efficacy in targeting the MAPK pathway, which is often overactive in uveal melanoma. Other treatments, such as immune checkpoint inhibitors (e.g., pembrolizumab and nivolumab), have also been explored for their potential benefits in managing metastatic uveal melanoma. These therapies aim to inhibit pathways critical for tumor growth and progression, similar to the investigational combination of defactinib and VS-6766.

What other types of research exist?

Promising novel alternatives to Defactinib and VS-6766 for uveal melanoma patients in 2024 may include other MEK inhibitors like selumetinib or binimetinib, as well as emerging immunotherapies and targeted therapies such as kinase inhibitors. Participation in clinical trials for new treatments targeting specific genetic mutations in uveal melanoma could also be considered.

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Protein Kinase Inhibitor

Defactinib + VS-6766 for Uveal Melanoma

Phase 2

Waitlist Available

Led By Takami Sato

Research Sponsored by Thomas Jefferson University

Eligibility Criteria Checklist

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

Must have

Written (signed and dated) informed consent and be capable of cooperating with treatment and follow-up

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Must not have

Patients with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease

Major surgery within 4 weeks prior to entry to the study (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study and from which the patient has not yet recovered

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to 28 days after the last dose of treatment

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include issues affecting the heart, liver, digestive system due to drug interactions; vision problems in the unaffected eye; increased risk of infection; allergic reactions to inactive ingredients in the medication.

Eligibility Criteria

Inclusion Criteria

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

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I have signed and understand the consent form and can follow the treatment plan.

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I am fully active or can carry out light work.

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I agree to use effective birth control during and for 3 months after the trial.

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My heart pumps well, confirmed by a heart scan.

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My healthy eye does not have retinopathy or retinal vein occlusion.

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My cancer, originating in the eye, has spread to other parts.

Exclusion Criteria

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

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I cannot take pills by mouth or have issues absorbing them due to stomach surgery or active bowel inflammation.

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I haven't had major surgery in the last 4 weeks or minor surgery in the last 2 weeks.

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I have had issues like a hole in my stomach or intestines or severe gut infections.

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I do not have severe heart or lung conditions.

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I have a serious health condition not related to cancer, like an uncontrolled infection.

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I have pancreatitis.

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I have Gilbert syndrome with high bilirubin levels but no liver damage.

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I have eye conditions in the eye not affected by uveal melanoma.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 28 days after the last dose of treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 28 days after the last dose of treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 28 days after the last dose of treatment for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Best overall response

Disease control rate

Secondary study objectives

Incidence of adverse events

Overall Survival (OS)

Progression-free Survival (PFS)

Other study objectives

Changes in apoptosis induction (caspase activation)

Changes in cell proliferation (Ki67)

Changes in signaling to the ERK, YAP, FAK, and PI3K TOR pathways

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1150

0 / 14Eligibility 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

The most common treatments for Uveal Melanoma, such as the combination of Defactinib and VS-6766, work by blocking overactive cell signaling pathways that are crucial for tumor growth and survival. Defactinib inhibits focal adhesion kinase (FAK), which is involved in cell adhesion and migration, while VS-6766 targets the RAF/MEK/ERK pathway, which is essential for cell division and proliferation. By disrupting these pathways, these treatments aim to reduce tumor growth and spread, offering potential stabilization or shrinkage of the cancer. This is particularly important for Uveal Melanoma patients as these pathways are often overactive in their tumor cells, leading to aggressive disease progression.

The Molecular Pathology of Eye Tumors: A 2019 Update Main Interests for Routine Clinical Practice.