40 Participants Needed

Avutometinib + Defactinib for Endometrial Cancer

Recruiting at 7 trial locations
CA
Rachel Grisham, MD profile photo
Overseen ByRachel Grisham, MD
Age: 18+
Sex: Female
Trial Phase: Phase 2
Sponsor: Memorial Sloan Kettering Cancer Center
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

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but you cannot take certain medications that interact with the study drugs. Specifically, you must avoid strong CYP3A4, CYP2C9, and P-glycoprotein inhibitors or inducers, as well as strong breast cancer resistance protein inhibitors or inducers, within 14 days before starting the trial and during the trial. If you are on warfarin, you will need to switch to another anticoagulant.

Will I have to stop taking my current medications?

The trial requires stopping certain medications that interact with the study drugs, such as strong CYP3A4, CYP2C9, and P-glycoprotein inhibitors or inducers, 14 days before starting the trial. If you are on warfarin, you may need to switch to another blood thinner.

What data supports the idea that Avutometinib + Defactinib for Endometrial Cancer is an effective drug?

The available research does not provide specific data on the effectiveness of Avutometinib + Defactinib for Endometrial Cancer. The studies mentioned focus on other drug combinations for different types of cancer, such as melanoma and colorectal cancer, and do not include information on Avutometinib + Defactinib for Endometrial Cancer. Therefore, there is no direct evidence from the provided information to support the effectiveness of this drug combination for Endometrial Cancer.12345

What safety data is available for Avutometinib and Defactinib in endometrial cancer treatment?

The provided research does not contain specific safety data for Avutometinib (VS-6766) and Defactinib (VS-6063) in the treatment of endometrial cancer. The studies focus on other BRAF and MEK inhibitors like vemurafenib, dabrafenib, trametinib, and selumetinib in melanoma and lung cancer, which have different safety profiles. Therefore, specific safety data for Avutometinib and Defactinib would need to be sourced from clinical trials or studies directly involving these drugs.678910

Is the drug Avutometinib (VS-6766) and Defactinib a promising treatment for endometrial cancer?

The drug Avutometinib (VS-6766) combined with Defactinib shows promise because similar drugs have been effective in treating other types of cancer, like lung cancer, by targeting specific mutations. This suggests potential for success in treating endometrial cancer as well.311121314

What makes the drug Avutometinib + Defactinib unique for endometrial cancer?

Avutometinib and Defactinib work together to target specific pathways in cancer cells, potentially offering a new approach for treating endometrial cancer by inhibiting both Raf/MEK and FAK pathways, which are involved in cancer cell growth and survival. This combination is being explored for its potential to provide a more effective treatment option compared to standard therapies.311121314

What is the purpose of this trial?

This study will test if Avutometinib (VS-6766) in combination with Defactinib is an effective treatment for advanced or recurrent mesonephric gynecologic cancer.

Research Team

Rachel N. Grisham, MD - MSK Gynecologic ...

Rachel Grisham, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for women over 18 with advanced or recurrent mesonephric gynecologic cancer. They must have good kidney and liver function, no severe heart issues, and cannot be pregnant or breastfeeding. Prior treatment with certain inhibitors or a history of rhabdomyolysis excludes participation.

Inclusion Criteria

My cancer is confirmed as GMC or has GMC characteristics according to my doctor.
My cancer has spread or returned after treatment.
My heart pumps well, with an ejection fraction of 50% or higher.
See 12 more

Exclusion Criteria

I cannot take pills by mouth or have issues absorbing food due to stomach surgery.
I haven't had major surgery in the last 4 weeks, minor surgery in the last 2 weeks, or palliative radiotherapy in the last week.
I have been treated with a MEK, RAF, or FAK inhibitor before.
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Avutometinib (VS-6766) and Defactinib for 3 weeks followed by a 1 week rest period in each 4-week cycle

2 years
Visits every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Avutometinib (VS-6766)
  • Defactinib
Trial Overview The study tests the effectiveness of Avutometinib (VS-6766) combined with Defactinib in treating mesonephric gynecologic cancers that are either persistent after first-line therapy or have returned after treatment.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Avutometinib (VS-6766) and DefactinibExperimental Treatment2 Interventions
All enrolled patients will be treated with Avutometinib (VS-6766) 3.2 mg PO, twice weekly (e.g. M/Th,Tu/F, or W/Sa) + defactinib 200 mg PO BID for 3 weeks, followed by a 1 week rest period, in each 4-week (28 day) cycle.

Avutometinib (VS-6766) is already approved in United States for the following indications:

๐Ÿ‡บ๐Ÿ‡ธ
Approved in United States as Avutometinib for:
  • Recurrent low-grade serous ovarian cancer (Breakthrough Therapy Designation)

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Verastem, Inc.

Industry Sponsor

Trials
42
Recruited
2,800+

Findings from Research

A network meta-analysis of three phase-3 trials involving 1230 patients found that the combinations of BRAF and MEK inhibitors (dabrafenib plus trametinib, vemurafenib plus cobimetinib, and encorafenib plus binimetinib) showed similar efficacy in terms of overall survival, progression-free survival, and overall response rate for treating advanced BRAF V600 mutated malignant melanoma.
While the efficacy of these drug combinations was comparable, the safety profiles varied slightly, indicating that specific molecular properties of each drug combination may influence the types and rates of side effects experienced by patients.
Network indirect comparison of 3 BRAF + MEK inhibitors for the treatment of advanced BRAF mutated melanoma.Consoli, F., Bersanelli, M., Perego, G., et al.[2022]
The study found that the combination of encorafenib and trametinib showed the highest anti-tumor activity, effectively suppressing cell proliferation and inducing apoptosis in both BRAF and NRAS mutant melanoma cells.
Encouragingly, this combination also delayed the development of resistance more effectively than currently approved treatments, suggesting it could lead to better outcomes for patients with melanoma.
Head-to-Head Comparison of BRAF/MEK Inhibitor Combinations Proposes Superiority of Encorafenib Plus Trametinib in Melanoma.Schulz, A., Raetz, J., Karitzky, PC., et al.[2022]
In the BEACON CRC study involving 665 patients with BRAF V600E-mutant metastatic colorectal cancer, the combination of encorafenib and cetuximab significantly improved overall survival (OS) to 9.3 months compared to 5.9 months for standard chemotherapy, indicating its efficacy as a treatment option.
The triplet regimen of encorafenib, binimetinib, and cetuximab achieved a confirmed objective response rate (ORR) of 26.8%, demonstrating a substantial improvement over the control group's ORR of only 1.8%, while maintaining a manageable safety profile with similar rates of grade โ‰ฅ 3 adverse events.
Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study.Tabernero, J., Grothey, A., Van Cutsem, E., et al.[2022]

References

Network indirect comparison of 3 BRAF + MEK inhibitors for the treatment of advanced BRAF mutated melanoma. [2022]
Head-to-Head Comparison of BRAF/MEK Inhibitor Combinations Proposes Superiority of Encorafenib Plus Trametinib in Melanoma. [2022]
Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study. [2022]
BRAF v600E-mutant cancers treated with vemurafenib alone or in combination with everolimus, sorafenib, or crizotinib or with paclitaxel and carboplatin (VEM-PLUS) study. [2023]
Improved survival with vemurafenib in melanoma with BRAF V600E mutation. [2022]
Study Design and Rationale for a Randomized, Placebo-Controlled, Double-Blind Study to Assess the Efficacy and Safety of Selumetinib in Combination With Docetaxel as Second-Line Treatment in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer (SELECT-1). [2018]
Skin toxicity in BRAF(V600) mutated metastatic cutaneous melanoma patients treated with vemurafenib. [2020]
Uveitis and Papillitis in the Setting of Dabrafenib and Trametinib Therapy for Metastatic Melanoma: A Case Report. [2018]
[BRAF-MEK inhibitor therapy in melanoma]. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Vemurafenib in patients with BRAF V600E mutation-positive advanced melanoma. [2018]
Single agent VS-6766 or VS-6766 plus defactinib in KRAS-mutant non-small-cell lung cancer: the RAMP-202 phase II trial. [2022]
12.United Statespubmed.ncbi.nlm.nih.gov
Phase II Study of Docetaxel and Trametinib in Patients with KRAS Mutation Positive Recurrent Non-Small Cell Lung Cancer (NSCLC; SWOG S1507, NCT-02642042). [2023]
NEXUS trial: a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant colorectal oligometastases. [2023]
Apatinib Mesylate Inhibits the Proliferation and Metastasis of Epithelioid Malignant Peritoneal Mesothelioma In Vitro and In Vivo. [2022]
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