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NCT06072781PHASE3Recruiting

A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer

Verastem, Inc.

Start Date

3/18/2024

Completion Date

2/9/2031

Summary

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.

Detailed Description

This international, randomized, open-label, Phase 3 study will compare the investigational combination of avutometinib plus defactinib versus Investigator's Choice of Treatments (ICT) in patients with recurrent LGSOC who have progressed on a prior platinum-based therapy. Avutometinib and defactinib are both types of drugs called kinase inhibitors. Kinase inhibitors block cancer cell growth. The study will compare the progression-free survival (PFS) of the combination of avutometinib plus defactinib versus ICT. The study will also evaluate the effect of the combination on safety, overall survival, other efficacy endpoints, and health-related quality of life and disease related symptoms. The study is being conducted by gynecological cancer specialists. Patients who are eligible and agree to participate in this study will be treated with either a combination of avutometinib with defactinib, or with one of four standard of care NCCN and ESMO treatment recommendations for recurrent LGSOC, and then with subsequent follow up appointments. Patients who originally received one of the standards of care treatments who are determined to have progressive disease may be eligible to crossover to receive the investigational combination avutometinib plus defactinib.Avutometinib and defactinib are investigational drugs that have not been approved by the U.S. Food and Drug Administration (FDA)

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

avutometinib

DRUG

Defactinib

DRUG

Pegylated liposomal doxorubicin

DRUG

Paclitaxel

DRUG

Letrozole

DRUG

Anastrozole

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Conditions

Low Grade Serous Ovarian Cancer

Locations

HonorHealth

Phoenix, Arizona 85016

United States

University of Arkansas

Little Rock, Arkansas 72205

United States

UCLA Health

Los Angeles, California 90095

United States

UC Davis

Sacramento, California 95817

United States

University of California, San Francisco

San Francisco, California 94143

United States

Yale University

New Haven, Connecticut 06520

United States

Florida Cancer Specialists - South

Fort Myers, Florida 33901

United States

Mount Sinai

Miami Beach, Florida 33140

United States

AdventHealth

Orlando, Florida 32804

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Florida Cancer Specialists Research East

West Palm Beach, Florida 33401

United States

Winship Cancer Institute at Emory University

Atlanta, Georgia 30322

United States

NorthShore University HealthSystem

Evanston, Illinois 60201

United States

Louisiana State University

New Orleans, Louisiana 70112

United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland 21287

United States

Karmanos Cancer Center

Detroit, Michigan 48201

United States

Minnesota Oncology Hematology

Minneapolis, Minnesota 55404

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Roswell Park Cancer Institute

Buffalo, New York 14263

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

Atrium Health

Charlotte, North Carolina 28203

United States

Cleveland Clinic Foundation

Cleveland, Ohio 44195

United States

Ohio State

Hilliard, Ohio 43026

United States

University of Oklahoma Medical Center

Oklahoma City, Oklahoma 73104

United States

Willamette Valley Cancer Institute

Eugene, Oregon 97401

United States

Northwest Cancer Specialists

Portland, Oregon 97227

United States

Asplundh Cancer Pavilion | Jefferson Health

Philadelphia, Pennsylvania 19090

United States

Allegheny Health Network

Pittsburgh, Pennsylvania 15224

United States

Texas Oncology Central

Austin, Texas 78731

United States

Texas Oncology-Fort Worth Cancer Center

Fort Worth, Texas 76104

United States

Houston Methodist

Houston, Texas 77030

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Texas Oncology

San Antonio, Texas 78229

United States

Texas Oncology

The Woodlands, Texas 77380

United States

Texas Oncology

Tyler, Texas 75702

United States

Intermountain Medical Center

Murray, Utah 84107

United States

University of Virginia Health System

Charlottesville, Virginia 22908

United States

Virginia Cancer Specialists, PC

Gainesville, Virginia 20155

United States

Prince of Wales Hospital

Randwick, New South Wales 2031

Australia

Icon Cancer Centre Wesley

Auchenflower, Queensland 4066

Australia

Cancer Research South Australia

Adelaide, South Australia 5000

Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia 6009

Australia

UZA

Edegem, 2650

Belgium

University Hospital Ghent

Ghent, 9000

Belgium

Princess Margaret Cancer Center

Toronto, Ontario M5G 1X6

Canada

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec H2X 0C1

Canada

McGill University Health Centre

Montreal, Quebec H4A 3J1

Canada

British of Columbia

Vancouver, V5Z 4E6

Canada

Aalborg U.H

Aalborg, 9000

Denmark

Centre Hospitalier de Besançon

Besançon, 25000

France

Site Georges François Leclerc

Dijon, 21079

France

Centre Oscar Lambret

Lille, 59020

France

Centre Léon Bérard

Lyon, 69373

France

Institut Curie

Paris,

France

Agaplesion Markus Krankenhaus

Frankfurt am Main, Hesse 60431

Germany

Charité - Universitätsmedizin Berlin

Berlin, 13353

Germany

Universitätsklinikum Carl Gustav Carus

Dresden, 01307

Germany

Kliniken Essen-Mitte

Essen, 45136

Germany

UMC Hamburg-Eppendorf

Hamburg, 20246

Germany

Universitätsklinikum Mannheim GmbH

Mannheim, 68167

Germany

Universitätsfrauenkinik Ulm

Ulm, 89075

Germany

St. James's Hospital

Dublin, 08

Ireland

Centro di Riferimento Oncologico (CRO)

Aviano, 33081

Italy

Spedali Civili

Brescia, 25123

Italy

AO Cannizzaro

Catania, 95126

Italy

San Raffaele Hospital

Milan, 20132

Italy

Humanitas San Pio X

Milan, 20159

Italy

European Institute of Oncology (IEO)

Milan,

Italy

Istituto Nazionale dei Tumori

Milan, 20133

Italy

INT Napoli Hospital

Naples,

Italy

Istituto Oncologico Veneto (IOV)

Padova, 35128

Italy

IRCCS Gemelli

Roma, 00168

Italy

Istituti Fisioterapici Ospitalieri

Rome, 00144

Italy

S.C.D.U. Oncologia

Torino, 10128

Italy

The Mie University Hospital

Tsu, Mie-ken 514-8507

Japan

Aichi Cancer Center Hospital

Aichi, Nagoya 464-8681

Japan

Tohoku University Hospital

Miyagi, 980-8574

Japan

Osaka Medical Center

Osaka,

Japan

The Jikei University Hospital

Tokyo, 3-19-18

Japan

Netherlands Cancer Insitute

Amsterdam, 1066

Netherlands

Radboud UMC

Nijmegen, 6525 GA

Netherlands

Auckland City Hospital

Auckland, 1023

New Zealand

Białostockie Centrum Onkologii

Bialystok, 15-027

Poland

Gdański Uniwersytet Medyczny

Gdansk, 80-214

Poland

Siedleckie Centrum Onkologii

Siedlce, 98-110

Poland

Seoul National University Bundang Hospital

Seongnam, 13620

South Korea

Yonsei University Severance Hospital

Seoul, 03722

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Gangnam Severance Hospital

Seoul, 06273

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Clínico Virgen de La Arrixaca

El Palmar, Murcia 30120

Spain

H. de Donostia

Donostia / San Sebastian, San Sebastian 20014

Spain

H. Vall d´ Hebron

Barcelona,

Spain

Hospital Universitario Reina Sofía

Córdoba,

Spain

H.U. Ramón y Cajal

Madrid,

Spain

Hospital Clínico Universitario de Santiago

Santiago de Compostela, 15706

Spain

Hospital Clínico Universitario de Valencia

Valencia, 46010

Spain

Greater Glasgow and Clyde (GGC)

Glasgow, Scotland G120YN

United Kingdom

Cambridge University Hospital

Cambridge, CB2 0QQ

United Kingdom

University of Edinburgh Cancer Research Centre

Edinburgh,

United Kingdom

Hope Cancer Trials Centre

Leicester, LE2 7LX

United Kingdom

University College London Hospitals NHS Foundation Trust

London, NW1 2PG

United Kingdom

Royal Marsden Hospital

London, SW7 3RP

United Kingdom

The Christie NHS Foundation Trust

Manchester,

United Kingdom

Royal Marsden Hospital

Sutton, SM2 5PT

United Kingdom