What side effects are associated with this type of intervention?

Common treatments for ovarian cancer, particularly those involving kinase inhibitors like Avutometinib (VS-6766), often have side effects such as fatigue, gastrointestinal issues (nausea, vomiting, diarrhea), and skin reactions (rash, dermatitis). Other targeted therapies, such as mTOR inhibitors, can cause serious toxicities including pneumonitis, mucositis, and gastrointestinal complications. Chemotherapy agents, frequently used in ovarian cancer treatment, typically result in side effects like neutropenia, anemia, thrombocytopenia, and peripheral neuropathy. It's important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of ovarian cancer, particularly focusing on inhibitors of key signaling pathways. One notable example is the approval of PARP inhibitors such as olaparib, niraparib, and rucaparib, which target DNA repair mechanisms and are used in patients with BRCA mutations or homologous recombination deficiencies. Additionally, bevacizumab, an angiogenesis inhibitor, has been approved for use in combination with chemotherapy for ovarian cancer. While specific RAF/MEK inhibitors like Avutometinib (VS-6766) are still under investigation, these approvals highlight the trend towards targeted therapies in the treatment of ovarian cancer.

What other types of research exist?

Promising novel alternatives to Avutometinib (VS-6766) for ovarian cancer patients include: 1) PI3K/PTEN/AKT/mTOR pathway inhibitors such as Temsirolimus and Everolimus, which have shown some promise in clinical trials. 2) Bevacizumab, an angiogenesis inhibitor, which has been used in combination with other agents to improve outcomes. 3) PARP inhibitors like Olaparib, which are particularly effective in patients with BRCA mutations. These alternatives are being actively studied and have shown potential benefits in ovarian cancer treatment.

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Kinase Inhibitor

Avutometinib vs. Avutometinib + Defactinib for Ovarian Cancer (RAMP 201 Trial)

Phase 2

Waitlist Available

Led By Susana Banerjee, MBBS,MA,PhD

Research Sponsored by Verastem, Inc.

Eligibility Criteria Checklist

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

Must have

Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease

Histologically proven LGSOC (ovarian, peritoneal)

Must not have

Subjects with the inability to swallow oral medications

Major surgery within 4 weeks

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests avutometinib alone and with defactinib in patients with recurrent Low-Grade Serous Ovarian Cancer. The drugs work by blocking cancer cell growth and survival signals.

Who is the study for?

This trial is for individuals with recurrent Low-Grade Serous Ovarian Cancer who've had at least one prior treatment. Participants must have good organ function, manageable side effects from previous treatments, measurable disease, and an ECOG performance status ≤ 1. They should not have severe concurrent diseases or a recent history of certain conditions like SARS-CoV-2 infection.

What is being tested?

The study is testing the effectiveness and safety of avutometinib alone versus in combination with defactinib for those with LGSOC. It aims to see which treatment works better for patients who have seen their cancer return after other therapies.

What are the potential side effects?

Potential side effects may include skin reactions, eye disorders if pre-existing, muscle breakdown (rhabdomyolysis), heart issues or severe lung problems if already present. Side effects specific to the drugs will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

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

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My low-grade serous ovarian cancer has worsened after treatment.

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My cancer is low-grade serous ovarian or peritoneal.

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I am fully active and can carry on all my pre-disease activities without restriction.

Exclusion Criteria

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

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I cannot swallow pills.

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I have not had major surgery in the last 4 weeks.

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I have high-grade ovarian cancer or another type of cancer.

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I have heart disease or severe lung problems.

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I experienced severe side effects from a previous MEK inhibitor treatment.

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I have had rhabdomyolysis before.

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I have an eye condition.

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I need medication or treatment for brain cancer symptoms.

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I have had cancer that came back less than 3 years ago.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Part A: Determine optimal regimen of avutometinib (VS-6766) monotherapy or in combination with defactinib

Part B: To determine the efficacy of the optimal regimen identified from Part A

Part C: To evaluate additional efficacy parameters for the optimal regimen identified in Part A

+1 more

Secondary study objectives

Disease Control Rate (DCR)

Duration of Response (DOR)

Overall Response Rate as assessed by Investigator

+2 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Part DExperimental Treatment1 Intervention

To evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib

Group II: Part C:Experimental Treatment1 Intervention

To evaluate additional efficacy parameters for the optimal regimen identified in Part A.

Group III: Part BExperimental Treatment2 Interventions

To determine the efficacy of the optimal regimen identified from Part A

Group IV: Part AExperimental Treatment2 Interventions

To determine the optimal regimen, either avutometinib(VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, for subsequent evaluation for efficacy in the Expansion Phase (Part B)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

avutometinib (VS-6766)

2020

Completed Phase 2

~90

0 / 12Eligibility 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

Ovarian cancer treatments often target specific molecular pathways to inhibit tumor growth and proliferation. Avutometinib (VS-6766) is a dual RAF/MEK inhibitor that blocks the RAF/MEK/ERK signaling pathway, which is crucial for cell division and survival, particularly in cancers with mutations in these pathways. This inhibition can reduce tumor growth and potentially lead to cancer cell death. PARP inhibitors, another common treatment, target the DNA repair mechanisms in cancer cells, particularly effective in tumors with BRCA mutations, leading to cell death due to accumulated DNA damage. Platinum-based chemotherapies, such as cisplatin and carboplatin, cause DNA cross-linking and damage, preventing cancer cells from replicating. Understanding these mechanisms helps ovarian cancer patients and their doctors choose the most effective treatment based on the tumor's specific genetic and molecular profile.