Clinical trial NCT04625270: A Study of Avutometinib (VS-6766) v. Avutometinib (VS-6766) + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer With and Without a KRAS Mutation
Official title: A Phase 2 Study of Avutometinib (VS-6766) (Dual RAF/MEK Inhibitor) Alone and In Combination With Defactinib (FAK Inhibitor) in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Low Grade Ovarian Serous Adenocarcinoma
Ovarian Cancer
Keywords: Low Grade Serous Ovarian Cancer
KRAS, KRAS wt
Lead sponsor: Verastem, Inc.
Sponsor class: INDUSTRY
Collaborators: name: European Network of Gynaecological Oncological Trial Groups (ENGOT)
name: GOG Foundation
First posted: 2020-11-12
Enrollment: 225
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy and in combination with defactinib in subjects with recurrent Low-Grade Serous Ovarian Cancer (LGSOC)

Detailed description: This is a multicenter, randomized, open-label Phase 2 study designed to evaluate safety and tolerability and preliminary efficacy of avutometinib (VS-6766) versus avutometinib (VS-6766) in combination with defactinib in subjects with molecularly profiled recurrent LGSOC.

Eligibility criteria: Inclusion Criteria:

* Histologically proven LGSOC (ovarian, peritoneal)
* Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
* Measurable disease according to RECIST 1.1
* An Eastern Cooperative Group (ECOG) performance status ≤ 1.
* Adequate organ function
* Adequate recovery from toxicities related to prior treatments
* Agreement to use highly effective method of contraceptive, if necessary

Exclusion Criteria:

* Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
* Co-existing high-grade ovarian cancer or another histology
* History of prior malignancy with recurrence \<3 years from the time of enrollment
* Major surgery within 4 weeks
* Symptomatic brain metastases requiring steroids or other interventions
* Known SARS-Cov2 infection (clinical symptoms) ≤28 days prior to first dose of study therapy
* For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor
* Active skin disorder that has required systemic therapy within the past year
* History of rhabdomyolysis
* Concurrent ocular disorders
* Concurrent heart disease or severe obstructive pulmonary disease
* Subjects with the inability to swallow oral medications

Primary outcomes:
measure: Part A: Determine optimal regimen of avutometinib (VS-6766) monotherapy or in combination with defactinib
timeFrame: From start of treatment to confirmation of response; 24 weeks
measure: Part B: To determine the efficacy of the optimal regimen identified from Part A
timeFrame: From start of treatment to confirmation of response; 24 weeks
measure: Part C: To evaluate additional efficacy parameters for the optimal regimen identified in Part A
timeFrame: From start of treatment to confirmation of response; 24 weeks
measure: Part D:To evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib
timeFrame: From start of treatment to confirmation of response; 24 weeks
Secondary outcomes:
measure: Overall Response Rate as assessed by Investigator
timeFrame: From start of treatment to confirmation of response; 24 weeks
measure: Duration of Response (DOR)
timeFrame: Time from the first documentation of response to first documentation of progressive disease or death due to any cause, greater than or equal to 6 months
measure: Disease Control Rate (DCR)
timeFrame: Greater than or equal to 8 weeks
measure: Progression Free Survival (PFS)
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Arizona Oncology Associates PC HAL
state: Arizona
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Orlando
country: United States
facility: Advent Health
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute - Center for Women's Oncology
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Glenn Dale
country: United States
facility: Maryland Oncology and Hematology, P.A.
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology PA
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center
state: New Mexico
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Women's Health Institute
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Medical Center
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology Austin Central
state: Texas
city: Dallas
country: United States
facility: Texas Oncology- Dallas Presbyterian Hospital
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Longview
country: United States
facility: Texas Oncology
state: Texas
city: McAllen
country: United States
facility: Texas Oncology
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Gainesville
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Gent
country: Belgium
facility: UZ Gent Medische Oncologie
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHU de Liege
city: Montréal
country: Canada
facility: Centre de recherche di Centre Hospitalier de i'Universite de Montreal
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: Besançon
country: France
facility: Hopital Jean Minjoz
city: Lyon
country: France
facility: Centre Leon Berard
city: Montpellier
country: France
facility: ICM - Val d'Aurelle
city: Paris
country: France
facility: Institut Curie
city: Milano
country: Italy
facility: Insituto Europeo di Oncologia I.R.C.C.S
city: Padova
country: Italy
facility: U.O.C. Oncologia 2, Istituto Oncologico Veneto I.R.C.C.S.
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D'Hebron
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: UCLH Cancer Clinical Trials Unit
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: European Network of Gynaecological Oncological Trial Groups (ENGOT)
name: Susana Banerjee, MBBS,MA,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: GOG Foundation
name: Rachel Grisham, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Verastem, Inc.
name: MD Verastem
role: STUDY_DIRECTOR
References: