Low Grade Serous Ovarian Cancer Clinical Trial
— RAMP 301Official title:
A Phase 3, Randomized, Open-Label Study of Combination Therapy With Avutometinib Plus Defactinib Versus Investigator's Choice of Treatment in Patients With Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) (RAMP 301)
This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with defactinib versus Investigator's choice of treatments (ICT) in subjects with recurrent LGSOC who have progressed on a prior platinum-based therapy.
| Status | Recruiting |
| Enrollment | 270 |
| Est. completion date | February 9, 2031 |
| Est. primary completion date | October 15, 2028 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility | 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. Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease. 3. Measurable disease according to RECIST v1.1. 4. An Eastern Cooperative Group (ECOG) performance status = 1. 5. Adequate organ function 6. Adequate recovery from toxicities related to prior treatments. 7. For patients with reproductive potential, Agreement to use highly effective method of contraceptive. 8. 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 ovarian cancer or another 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. 6. Symptomatic brain metastases or spinal cord compression. 7. An active skin disorder that has required systemic therapy within one year of signing informed consent. 8. History of medically significant rhabdomyolysis. 9. For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor. 10. Symptomatic bowel obstruction within 3 months. 11. Concurrent ocular disorders. 12. Concurrent heart disease or severe obstructive pulmonary disease. 13. Subjects with the inability to swallow oral medications. 14. Active, uncontrolled infection (bacterial, viral, or fungal) requiring systemic therapy. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Cancer Research South Australia | Adelaide | South Australia |
| Australia | Icon Cancer Centre Wesley | Auchenflower | Queensland |
| United Kingdom | Royal Marsden Hospital | London | |
| United Kingdom | University College London Hospitals NHS Foundation Trust | London | |
| United Kingdom | Royal Marsden Hospital | Sutton | |
| United States | Texas Oncology Central | Austin | Texas |
| United States | University of Virginia Health System | Charlottesville | Virginia |
| United States | Cleveland Clinic Foundation | Cleveland | Ohio |
| United States | Karmanos Cancer Center | Detroit | Michigan |
| United States | Willamette Valley Cancer Institute | Eugene | Oregon |
| United States | NorthShore University HealthSystem | Evanston | Illinois |
| United States | Texas Oncology-Fort Worth Cancer Center | Fort Worth | Texas |
| United States | Virginia Cancer Specialists, PC | Gainesville | Virginia |
| United States | Ohio State | Hilliard | Ohio |
| United States | UCLA Health | Los Angeles | California |
| United States | Minnesota Oncology Hematology | Minneapolis | Minnesota |
| United States | Yale University | New Haven | Connecticut |
| United States | Memorial Sloan Kettering Cancer Center | New York | New York |
| United States | University of Oklahoma Medical Center | Oklahoma City | Oklahoma |
| United States | AdventHealth | Orlando | Florida |
| United States | HonorHealth | Phoenix | Arizona |
| United States | Allegheny Health Network | Pittsburgh | Pennsylvania |
| United States | Northwest Cancer Specialists | Portland | Oregon |
| United States | Washington University School of Medicine | Saint Louis | Missouri |
| United States | Texas Oncology | San Antonio | Texas |
| United States | Texas Oncology | The Woodlands | Texas |
| United States | Texas Oncology | Tyler | Texas |
| United States | Florida Cancer Specialists Research East | West Palm Beach | Florida |
| Lead Sponsor | Collaborator |
|---|---|
| Verastem, Inc. | European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation |
United States, Australia, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression Free Survival (PFS) per blinded independent central review (BICR) | Confirmed overall response rate per RECIST 1.1 per blinded independent central review (BICR) | Up to 24 months | |
| Secondary | Overall Survival (OS) | From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause | Up to 5 years | |
| Secondary | Progression Free Survival (PFS) per investigator assessment | From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause | 24 months | |
| Secondary | Objective response rate (ORR) | From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause | 12 months | |
| Secondary | Duration of Response (DOR) | From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause | 12 months | |
| Secondary | Disease Control Rate (DCR) | CR+PR+Stable disease | 6 months | |
| Secondary | Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs) | Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale | 25 months | |
| Secondary | Area under the plasma concentration-time curve (AUC) of avutometinib, defactinib and relative metabolites | Area under plasma Concentration (AUC) 0 to t | 5 months | |
| Secondary | Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites | maximum plasma concentration | 5 months | |
| Secondary | To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Core module C30 (QLQ-C30). | The EORTC QLQ-C30 is a questionnaire to assess quality of life of ovarian cancer patients. It is composed of 30 questions. An overall scoring range is from 0 to 100. A high scales score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of function, a high score for the global health status/QOL represents a high QOL, but a high score for a symptom scale/item represents a high level of symptomatology/problems. Quality of life measured by EORTC QLQ-C30. These are validated questionnaires to be answered by patients. | 24 months | |
| Secondary | To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Ovarian Cancer module OV28 (QLQ-OV28). | The EORTC QLQ-OV28 is a questionnaire to assess quality of life of ovarian cancer patients. It is composed of 28 questions. An overall scoring range is from 0 to 100. A high scales score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of function, a high score for the global health status/QOL represents a high QOL, but a high score for a symptom scale/item represents a high level of symptomatology/problems. | 24 months |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT03875820 -
Phase I Trial of Defactinib and VS-6766.
|
Phase 1 |