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A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer
NCT06072781 · Verastem, Inc.
In plain English
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Official 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)
About this study
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
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.
Study design
Enrollment target: 270 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-03-18
Estimated completion: 2031-02-09
Last updated: 2026-04-02
Interventions
Drug: avutometinibDrug: DefactinibDrug: Pegylated liposomal doxorubicinDrug: PaclitaxelDrug: LetrozoleDrug: Anastrozole
Primary outcomes
- • Progression Free Survival (PFS) per blinded independent central review (BICR) (Up to 24 months)
Sponsor
Verastem, Inc. · industry
With: GOG Foundation, European Network of Gynaecological Oncological Trial Groups (ENGOT), Australia New Zealand Gynaecological Oncology Group, Korean Gynecologic Oncology Group
Contacts & investigators
ContactVerastem Call Center · contact · RAMP301TrialSupport@verastem.com · 781-292-4204
InvestigatorRachel Grisham, MD · principal_investigator, GOG Foundation
InvestigatorSusana Banerjee, MBBS, MA, PhD · principal_investigator, European Network of Gynecological Oncological Trial Groups (ENGOT)
InvestigatorCraig Berman Verastem Medical Monitor · study_director, RAMP301@verastem.com
All locations (106)
HonorHealthRecruiting
Phoenix, Arizona, United States
University of ArkansasRecruiting
Little Rock, Arkansas, United States
UCLA HealthRecruiting
Los Angeles, California, United States
UC DavisRecruiting
Sacramento, California, United States
University of California, San FranciscoRecruiting
San Francisco, California, United States
Yale UniversityRecruiting
New Haven, Connecticut, United States
Florida Cancer Specialists - SouthRecruiting
Fort Myers, Florida, United States
Mount SinaiRecruiting
Miami Beach, Florida, United States
AdventHealthRecruiting
Orlando, Florida, United States
Moffitt Cancer CenterRecruiting
Tampa, Florida, United States
Florida Cancer Specialists Research EastRecruiting
West Palm Beach, Florida, United States
Winship Cancer Institute at Emory UniversityRecruiting
Atlanta, Georgia, United States
NorthShore University HealthSystemRecruiting
Evanston, Illinois, United States
Louisiana State UniversityRecruiting
New Orleans, Louisiana, United States
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsRecruiting
Baltimore, Maryland, United States
Karmanos Cancer CenterRecruiting
Detroit, Michigan, United States
Minnesota Oncology HematologyRecruiting
Minneapolis, Minnesota, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Roswell Park Cancer InstituteRecruiting
Buffalo, New York, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
Atrium HealthRecruiting
Charlotte, North Carolina, United States
Cleveland Clinic FoundationRecruiting
Cleveland, Ohio, United States
Ohio StateRecruiting
Hilliard, Ohio, United States
University of Oklahoma Medical CenterRecruiting
Oklahoma City, Oklahoma, United States
Willamette Valley Cancer InstituteRecruiting
Eugene, Oregon, United States
Northwest Cancer SpecialistsRecruiting
Portland, Oregon, United States
Asplundh Cancer Pavilion | Jefferson HealthRecruiting
Philadelphia, Pennsylvania, United States
Allegheny Health NetworkRecruiting
Pittsburgh, Pennsylvania, United States
Texas Oncology CentralRecruiting
Austin, Texas, United States
Texas Oncology-Fort Worth Cancer CenterRecruiting
Fort Worth, Texas, United States
Houston MethodistRecruiting
Houston, Texas, United States
MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
Texas OncologyRecruiting
San Antonio, Texas, United States
Texas OncologyRecruiting
The Woodlands, Texas, United States
Texas OncologyRecruiting
Tyler, Texas, United States
Intermountain Medical CenterRecruiting
Murray, Utah, United States
University of Virginia Health SystemRecruiting
Charlottesville, Virginia, United States
Virginia Cancer Specialists, PCRecruiting
Gainesville, Virginia, United States
Prince of Wales HospitalRecruiting
Randwick, New South Wales, Australia
Icon Cancer Centre WesleyRecruiting
Auchenflower, Queensland, Australia
Cancer Research South AustraliaRecruiting
Adelaide, South Australia, Australia
Peter MacCallum Cancer CentreRecruiting
Melbourne, Victoria, Australia
Sir Charles Gairdner HospitalRecruiting
Nedlands, Western Australia, Australia
UZARecruiting
Edegem, Belgium
University Hospital GhentRecruiting
Ghent, Belgium
Princess Margaret Cancer CenterRecruiting
Toronto, Ontario, Canada
Centre Hospitalier de l'Universite de Montreal (CHUM)Recruiting
Montreal, Quebec, Canada
McGill University Health CentreRecruiting
Montreal, Quebec, Canada
British of ColumbiaRecruiting
Vancouver, Canada
Aalborg U.HRecruiting
Aalborg, Denmark
Centre Hospitalier de BesançonRecruiting
Besançon, France
Site Georges François LeclercRecruiting
Dijon, France
Centre Oscar LambretRecruiting
Lille, France
Centre Léon BérardRecruiting
Lyon, France
Institut CurieRecruiting
Paris, France
Agaplesion Markus KrankenhausRecruiting
Frankfurt am Main, Hesse, Germany
Charité - Universitätsmedizin BerlinRecruiting
Berlin, Germany
Universitätsklinikum Carl Gustav CarusRecruiting
Dresden, Germany
Kliniken Essen-MitteRecruiting
Essen, Germany
UMC Hamburg-EppendorfRecruiting
Hamburg, Germany
Universitätsklinikum Mannheim GmbHRecruiting
Mannheim, Germany
Universitätsfrauenkinik UlmRecruiting
Ulm, Germany
St. James's HospitalRecruiting
Dublin, Ireland
Centro di Riferimento Oncologico (CRO)Recruiting
Aviano, Italy
Spedali CiviliRecruiting
Brescia, Italy
AO CannizzaroRecruiting
Catania, Italy
San Raffaele HospitalRecruiting
Milan, Italy
Humanitas San Pio XRecruiting
Milan, Italy
European Institute of Oncology (IEO)Recruiting
Milan, Italy
Istituto Nazionale dei TumoriRecruiting
Milan, Italy
INT Napoli HospitalRecruiting
Naples, Italy
Istituto Oncologico Veneto (IOV)Recruiting
Padova, Italy
IRCCS GemelliRecruiting
Roma, Italy
Istituti Fisioterapici OspitalieriRecruiting
Rome, Italy
S.C.D.U. OncologiaRecruiting
Torino, Italy
The Mie University HospitalRecruiting
Tsu, Mie-ken, Japan
Aichi Cancer Center HospitalRecruiting
Aichi, Nagoya, Japan
Tohoku University HospitalRecruiting
Miyagi, Japan
Osaka Medical CenterRecruiting
Osaka, Japan
The Jikei University HospitalRecruiting
Tokyo, Japan
Netherlands Cancer InsituteRecruiting
Amsterdam, Netherlands
Radboud UMCRecruiting
Nijmegen, Netherlands
Auckland City HospitalRecruiting
Auckland, New Zealand
Białostockie Centrum OnkologiiRecruiting
Bialystok, Poland
Gdański Uniwersytet MedycznyRecruiting
Gdansk, Poland
Siedleckie Centrum OnkologiiRecruiting
Siedlce, Poland
Seoul National University Bundang HospitalRecruiting
Seongnam, South Korea
Yonsei University Severance HospitalRecruiting
Seoul, South Korea
Asan Medical CenterRecruiting
Seoul, South Korea
Gangnam Severance HospitalRecruiting
Seoul, South Korea
Samsung Medical CenterRecruiting
Seoul, South Korea
Clínico Virgen de La ArrixacaRecruiting
El Palmar, Murcia, Spain
H. de DonostiaRecruiting
Donostia / San Sebastian, San Sebastian, Spain
H. Vall d´ HebronRecruiting
Barcelona, Spain
Hospital Universitario Reina SofíaRecruiting
Córdoba, Spain
H.U. Ramón y CajalRecruiting
Madrid, Spain
Hospital Clínico Universitario de SantiagoRecruiting
Santiago de Compostela, Spain
Hospital Clínico Universitario de ValenciaRecruiting
Valencia, Spain
Greater Glasgow and Clyde (GGC)Recruiting
Glasgow, Scotland, United Kingdom
Cambridge University HospitalRecruiting
Cambridge, United Kingdom
University of Edinburgh Cancer Research CentreRecruiting
Edinburgh, United Kingdom
Hope Cancer Trials CentreRecruiting
Leicester, United Kingdom
University College London Hospitals NHS Foundation TrustRecruiting
London, United Kingdom
Royal Marsden HospitalRecruiting
London, United Kingdom
The Christie NHS Foundation TrustRecruiting
Manchester, United Kingdom
Royal Marsden HospitalRecruiting
Sutton, United Kingdom