Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) MedDRA version: 21.1 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Verastem, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects may be eligible for inclusion in the study if they meet the following criteria: 1. Female subjects = 18 years of age 2. Histologically proven LGSOC (ovarian, peritoneal) a. The Sponsor’s Medical Monitor must review the pathology report prior to the start of treatment b. Adequate pathology material (as defined in the lab manual) must be available prior to enrollment to be used for central confirmation. Central pathological confirmation does not need to be completed prior to enrollment. 3. Tumor with known KRAS mutation using a validated testing method (blood or tissue) prior to treatment assignment. Adequate archival tumor tissue less than 5 years old or fresh biopsy tissue samples (as defined in the lab manual) must be available for central confirmation prior to treatment assignment. 4. Progression (radiographic or clinical) or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease. Below are additional prior treatments that are allowed once the requirement of prior platinum therapy is satisfied. a. Prior systemic therapy for metastatic disease (FIGO stage II-IV) may consist of chemotherapy administered as single agent or a platinum or another chemotherapy doublet with or without bevacizumab, with or without maintenance therapy or radiation therapy; hormonal therapy; and/or MEK/RAF inhibitor therapy. b. Only one prior line of MEK/RAF inhibitor therapy is allowed. 5. Measurable disease according to RECIST 1.1. Measurable disease status must be confirmed by independent radiology review. All radiology studies and confirmation must be performed within 28 days prior to randomization (Part A) or start of study-directed therapy in Part B. 6. An Eastern Cooperative Group (ECOG) performance status = 1. 7. Must have 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 has been administered the Hb must remain stable and =9 g/dL for at least 1 week prior to first dose of study therapy. b. Adequate hepatic function: (i) total bilirubin =1.5 × upper limit of normal [ULN] for the institution; subjects with Gilbert syndrome may enroll if total bilirubin <3.0 mg/dL (51 µmole/L) upon discussion with Medical Monitor. (ii) alanine aminotransferase (ALT) and alanine aminotransferase (AST) =2.5 × ULN (or <5x ULN in subjects with liver metastases. c. Adequate renal function with creatinine clearance rate of =60 mL/min as calculated by the Cockcroft-Gault formula. 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 µmole/L). f. Creatine phosphokinase (CPK) =2.5 x ULN. g. Adequate cardiac function with left ventricular ejection fraction = 50% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan. 8. Baseline QTc interval < 460 ms (average of triplicate readings) (CTCAE Grade 1) using Fredericia’s QT correction formula. NOTE: This criterion does not apply to subjects with a right or left bundle branch block. 9. Adequate recovery from toxicities related to prior treatments to at least Grade 1 by CTCAE v 5.0. Exceptions include alopecia and peripheral neuropathy Grade =2. Subjects with other toxicities that are stable on supportive therapy may be allo
Exclusion criteria
Exclusion criteria: Subjects 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. History of prior malignancy with recurrence 21 mm Hg as measured by tonometry, or other significant ocular pathology, such as anato
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: To determine the optimal regimen, either VS-6766 monotherapy or VS-6766 in combination with defactinib, for subsequent evaluation for efficacy in the expansion phase (Part B) Part B: To determine the efficacy of the optimal regimen identified from Part A;Secondary Objective: 1) To characterize the safety and toxicity profile of VS-6766 as a monotherapy and in combination with defactinib in LGSOC 2) Part A: To evaluate additional efficacy parameters for VS-6766 monotherapy and in combination with defactinib Part B: To evaluate additional efficacy parameters for the optimal regimen identified in Part A 3) To characterize the pharmacokinetics (PK) of VS-6766, defactinib, and relevant metabolites;Primary end point(s): Part A: Confirmed overall response rate (ORR; partial response [PR] + complete response [CR] defined according to RECIST 1.1) as assessed by the blinded independent radiology review committee (BIRC) Part B: Confirmed ORR defined according to RECIST 1.1 as assessed by the BIRC;Timepoint(s) of evaluation of this end point: throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A and B: 1) Adverse events (AEs), serious AEs (SAEs), physical examinations, clinical laboratory values and tolerability (dose interruptions/reductions) 2) - Duration of response (DOR) as assessed by the BIRC - ORR as assessed by the Investigator - Progression free survival (PFS), defined as the time from first dose of study treatment to the first documentation of PD, or death from any cause - Disease control rate (DCR), defined as CR+PR+ stable disease (SD) - Overall survival (OS) 3) PK parameters derived from plasma concentrations of VS-6766, defactinib, and relevant metabolites;Timepoint(s) of evaluation of this end point: throughout the study | — |
Countries
Belgium, Canada, France, Italy, Spain, United Kingdom, United States
Contacts
Public ContactGloria Patrick
Verastem, Inc.
Outcome results
None listed