Combination treatment for recurrent low-grade serous ovarian cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This international, randomized, open-label Phase 3 study evaluates the safety and efficacy of the investigational drugs avutometinib and defactinib in patients with recurrent low-grade serous ovarian cancer (LGSOC) who have progressed after platinum-based therapy. Participants will be assigned to receive either the combination of these two drugs or one of the standard treatments recommended by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO). The primary focus is on comparing progression-free survival (PFS) between the two groups, along with assessing safety, overall survival, and quality of life. The study aims to provide insights into the effectiveness of this novel combination therapy in managing recurrent LGSOC.

Why it matters

Who can join: the full rules

Inclusion Criteria:

Patients may be eligible for inclusion in the study if they meet the following criteria:

1. Histologically proven LGSOC (ovarian, fallopian, peritoneal)
2. Documented mutational status of KRAS by a validated tumor-tissue based diagnostic test.
3. Suitable for treatment with at least one of the Investigator's Choice of Treatments:pegylated liposomal doxorubicin, paclitaxel, letrozole, anastrozole.
4. Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
5. Measurable disease according to RECIST v1.1.
6. An Eastern Cooperative Group (ECOG) performance status ≤ 1.
7. Adequate organ function.
8. Adequate recovery from toxicities related to prior treatments.
9. For patients with reproductive potential, a negative pregnancy test must be confirmed and agreement to use highly effective method of contraceptive.
10. Willingness to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

1. Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
2. Co-existing high-grade serous ovarian cancer or mixed histology.
3. Prior treatment with avutometinib, defactinib, or other FAK inhibitors.
4. History of prior malignancy with recurrence \<3 years from the time of enrollment.
5. Major surgery within 4 weeks, minor surgery within 1 week, or palliative radiotherapy within 1 week of the first dose of study intervention.
6. Symptomatic brain metastases requiring steroids or other interventions, known leptomeningeal metastases, or spinal cord compression.
7. An active skin disorder that has required systemic therapy within one year of the first dose of study intervention.
8. History of medically significant rhabdomyolysis.
9. For subjects with prior MEK or RAF exposure, Grade 4 toxicity is deemed related to the MEK inhibitor.
10. Symptomatic bowel obstruction within 3 months of the first dose of study intervention
11. Concurrent ocular disorders.
12. Concurrent heart disease or severe obstructive pulmonary disease.
13. Active or past medical history of interstitial lung disease/pneumonitis, including drug-induced or radiation pneumonitis, pulmonary fibrosis, or adult respiratory distress syndrome (ARDS).
14. Subjects with the inability to swallow oral medications.
15. History of hypersensitivity to any of the active agents or ingredients of study intervention: peanut, soya, polyoxyl castor oil, etcetc.). Prior hypersensitivity to anthracyclines or anthracenediones if the use of pegylated liposomal doxorubicin (PLD) is planned.
16. Pregnant or breastfeeding.
17. Active, uncontrolled infection (bacterial, viral, or fungal) requiring systemic therapy.

Where it's running

• HonorHealth
  Phoenix, Arizona, United States Recruiting
• University of Arkansas
  Little Rock, Arkansas, United States Recruiting
• UCLA Health
  Los Angeles, California, United States Recruiting
• UC Davis
  Sacramento, California, United States Recruiting
• Yale University
  New Haven, Connecticut, United States Recruiting
• Florida Cancer Specialists - South
  Fort Myers, Florida, United States Recruiting

+55 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Principal investigator: Rachel Grisham, MD — GOG Foundation
• Study coordinator: Verastem Call Center
• Email: RAMP301TrialSupport@verastem.com
• Phone: 781-292-4204

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.