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) (RAMP301)
- Conditions
- Recurrent Low-Grade Serous Ovarian Cancer (LGSOC)Therapeutic area: Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]
- Registration Number
- CTIS2023-508204-38-00
- Lead Sponsor
- Verastem Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 295
Age = 18 years, Adequately recovered (Grade = 1 by CTCAE v 5.0) from any toxicities related to prior treatments except alopecia or hypothyroidism., For patients with reproductive potential, a negative serum pregnancy test (ß human chorionic gonadoptropnin [ß-hCG]) no more than 7 days prior to randomization, verified by the treating physician., For patients with reproductive potential, agreement to use highly effective method of contraceptive (per Clinical Trial Facilitation Group [CFTG] recommendations) during the trial and for 30 days following the last dose of study intervention, Willingness to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures., Histologically proven LGSOC (ovarian, fallopian, peritoneal) a. No mixed histology; LGSOC in conjunction with serous borderline tumor is permitted b. Adequate tumor tissue (as defined in the lab manual) must be available for central confirmation of LGSOC. Adequate tumor tissue (as defined in the lab manual) must be received by the central laboratory prior to randomization. If the patient does not have adequate archived tumor tissue or the archived tumor was obtained more than 5 years from informed consent, then a fresh tumor sample will be needed to support eligibility. Central pathological confirmation does not need to be completed prior to randomization., Suitable for treatment with at least one of the Investigator’s Choice of Treatments (ie, pegylated liposomal doxorubicin, paclitaxel, topotecan, letrozole, anastrozole) as determined by the Investigator, given the medical history, prior treatment(s), availability, and approval within a given country, and other relevant factors., Documented progression (radiographic or clinical) or recurrence of LGSOC after at least one platinum-based chemotherapy regimen. Allowed prior treatments and therapies include: a. Prior systemic therapy for metastatic disease (International Federation of Gynecology and Obstetrics [FIGO] stage II-IV) may consist of chemotherapy administered with or without bevacizumab, with or without maintenance therapy; or hormonal therapy. b. One prior line of treatment with a MEK and/or RAF inhibitor is permitted only if there was prior clinical benefit (objective response or stable disease = 6 months) and not received within 6 months of signing informed consent., Adequate organ function, defined by the following laboratory parameters: a. Adequate hematologic function, including hemoglobin [Hb] = 9.0 g/dL; platelets = 100,000/mm3; and absolute neutrophil count [ANC] = 1500/mm3. If a red blood cell transfusion or erythropoiesis-stimulating agent has been administered the Hb must remain stable and = 9 g/dL for at least 1 week prior to first dose of study intervention. b. Adequate hepatic function: (i) total bilirubin = 1.5 × upper limit of normal [ULN] for the institution; patients with Gilbert syndrome may enroll if total bilirubin is < 3.0 mg/dL (51 µmol/L); (ii) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN (or < 5 x ULN in patients with liver metastases). c. Adequate renal function with creatinine clearance rate of = 50 mL/min, as calculated by the Cockcroft-Gault formula or serum creatinine of = 1.5 x ULN. d. International normalized ratio (INR) = 1.5 and partial thromboplastin time (PTT) = 1.5 x ULN in the absence of anticoagulation or therapeutic levels in the presence of anticoagulation. e. Albumin = 3.0 g/dL (451 µmol/L). f. Creatine phosphokinas
Received a systemic (targets the entire body) cancer treatment within 4 weeks of the first dose of study therapy;, Have symptomatic brain cancer or a spinal cord involvement;, Have an active skin disorder that has required a systemic treatment within 1 year of signing informed consent;, Have a history of medically significant rhabdomyolysis (rare muscle injury where the muscles break down);, Have had a serious reaction to a MEK (mitogen-activated protein kinase kinase) inhibitor in the past;, Have had symptomatic bowel blockage within 3 months prior to treatment;, Currently have eye disorders;, Currently have heart disease or severe obstructive pulmonary disease;, Are not able to swallow medicines given by mouth; or Have active, uncontrolled infections (bacterial, viral, or fungal) requiring systemic therapy., Currently have high-grade ovarian cancer or another ovarian cancer subtype;, Have had prior treatment with avutometinib, defactinib, or other FAK kinase inhibitors similar to defactinib;, Have a history of prior cancer that came back less than 3 years from the time of enrollment;, Had a major surgery within 4 weeks prior to treatment;
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method