A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer (RAMP 301)

April 19, 2024 updated by: Verastem, Inc.

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)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 a type of drug called a kinase inhibitor. 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 five 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 standard 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)

Study Type

Interventional

Enrollment (Estimated)

270

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • Queensland
      • Auchenflower, Queensland, Australia, 4066
        • Recruiting
        • Icon Cancer Centre Wesley
        • Contact:
        • Principal Investigator:
          • Jeffrey Goh, MD
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Recruiting
        • Cancer Research South Australia
        • Contact:
        • Principal Investigator:
          • Meena Okera, MD
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University
        • Contact:
        • Principal Investigator:
          • Alessandro Santin, MD
    • Florida
    • Illinois
      • Evanston, Illinois, United States, 60201
        • Recruiting
        • NorthShore University Healthsystem
        • Principal Investigator:
          • Mary Tilley Jenkins-Vogel, MD
        • Contact:
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Center
        • Principal Investigator:
          • Robert Morris, MD
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Principal Investigator:
          • Premal Thaker, MD
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic Foundation
        • Principal Investigator:
          • Peter Rose, MD
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Medical Center
        • Principal Investigator:
          • Christina Washington, MD
        • Contact:
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Recruiting
        • Willamette Valley Cancer Institute
        • Principal Investigator:
          • Charles Anderson, MD
        • Contact:
      • Portland, Oregon, United States, 97227
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • Allegheny Health Network
        • Principal Investigator:
          • Thomas Krivak, MD
        • Contact:
    • Texas
      • Austin, Texas, United States, 78731
      • San Antonio, Texas, United States, 78229
      • The Woodlands, Texas, United States, 77380
      • Tyler, Texas, United States, 75702
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia Health System
        • Principal Investigator:
          • Kari Ring, MD
        • Contact:
      • Gainesville, Virginia, United States, 20155

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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. Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
  3. Measurable disease according to RECIST v1.1.
  4. An Eastern Cooperative Group (ECOG) performance status ≤ 1.
  5. Adequate organ function
  6. Adequate recovery from toxicities related to prior treatments.
  7. For patients with reproductive potential, Agreement to use highly effective method of contraceptive.
  8. 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 ovarian cancer or another 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.
  6. Symptomatic brain metastases or spinal cord compression.
  7. An active skin disorder that has required systemic therapy within one year of signing informed consent.
  8. History of medically significant rhabdomyolysis.
  9. For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor.
  10. Symptomatic bowel obstruction within 3 months.
  11. Concurrent ocular disorders.
  12. Concurrent heart disease or severe obstructive pulmonary disease.
  13. Subjects with the inability to swallow oral medications.
  14. Active, uncontrolled infection (bacterial, viral, or fungal) requiring systemic therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: avutometinib + defactinib
Avutometinib 3.2 mg, PO, twice weekly (eg, Monday/Thursday, Tuesday/Friday, or Wednesday/Saturday) for 21 days on, 7 days off in a 28-day (4 weeks) cycle in combination with defactinib 200 mg, PO, twice daily for 21 days on, 7 days off in a 28-day(4 week) cycle.
Drug: avutometinib
Avutometinib: administered orally
Other Names:
  • avutometinib (VS-6766)
Drug: Defactinib
Defactinib: administered orally
Other Names:
  • defactinib (VS-6063)
Active Comparator: Investigator Choice of Treatment (ICT)

Patients will receive one of the following therapies as determined by the Investigator:

  • Pegylated liposomal doxorubicin: 40 mg/m2 IV on Day 1 of each 28-day (4 week) cycle.
  • Paclitaxel: 80 mg/m2 IV on Days 1, 8, and 15 of each 28-day (4 week) cycle.
  • Topotecan: 4 mg/m2 IV on Days 1, 8, and 15 of each 28-day (4 week) cycle.
  • Anastrozole: 1 mg, PO, once daily of each 28-day (4 week) cycle.
  • Letrozole: 2.5 mg, PO, once daily of each 28-day (4 week) cycle.
Drug: Paclitaxel
administered intravenously
Other Names:
  • Nov-Onxol, Onxol, Navaplus, Taxol
Drug: Pegylated liposomal doxorubicin
administered intravenously
Other Names:
  • Caelyx, Doxil, Lipodox
Drug: Topotecan
administered intravenously
Other Names:
  • Hycamtin
Drug: Letrozole
administered orally
Other Names:
  • Femara
Drug: Anastrozole
administered orally
Other Names:
  • Arimidex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) per blinded independent central review (BICR)
Time Frame: Up to 24 months
Confirmed overall response rate per RECIST 1.1 per blinded independent central review (BICR)
Up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to 5 years
From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause
Up to 5 years
Progression Free Survival (PFS) per investigator assessment
Time Frame: 24 months
From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
24 months
Objective response rate (ORR)
Time Frame: 12 months
From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
12 months
Duration of Response (DOR)
Time Frame: 12 months
From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
12 months
Disease Control Rate (DCR)
Time Frame: 6 months
CR+PR+Stable disease
6 months
Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)
Time Frame: 25 months
Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale
25 months
Area under the plasma concentration-time curve (AUC) of avutometinib, defactinib and relative metabolites
Time Frame: 5 months
Area under plasma Concentration (AUC) 0 to t
5 months
Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites
Time Frame: 5 months
maximum plasma concentration
5 months
To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Core module C30 (QLQ-C30).
Time Frame: 24 months
The EORTC QLQ-C30 is a questionnaire to assess quality of life of ovarian cancer patients. It is composed of 30 questions. An overall scoring range is from 0 to 100. A high scales score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of function, a high score for the global health status/QOL represents a high QOL, but a high score for a symptom scale/item represents a high level of symptomatology/problems. Quality of life measured by EORTC QLQ-C30. These are validated questionnaires to be answered by patients.
24 months
To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Ovarian Cancer module OV28 (QLQ-OV28).
Time Frame: 24 months
The EORTC QLQ-OV28 is a questionnaire to assess quality of life of ovarian cancer patients. It is composed of 28 questions. An overall scoring range is from 0 to 100. A high scales score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of function, a high score for the global health status/QOL represents a high QOL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Verastem, Inc.

Collaborators

GOG Foundation
European Network of Gynaecological Oncological Trial Groups (ENGOT)

Investigators

  • Principal Investigator: Rachel Grisham, MD, GOG Foundation
  • Study Director: MD Verastem, Verastem, Inc.
  • Principal Investigator: Susana Banerjee, MBBS, MA, PhD, European Network of Gynecological Oncological Trial Groups (ENGOT)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 18, 2024

Primary Completion (Estimated)

October 15, 2028

Study Completion (Estimated)

February 9, 2031

Study Registration Dates

First Submitted

October 2, 2023

First Submitted That Met QC Criteria

October 2, 2023

First Posted (Actual)

October 10, 2023

Study Record Updates

Last Update Posted (Actual)

April 22, 2024

Last Update Submitted That Met QC Criteria

April 19, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VS-6766-301
  • GOG-3097 (Other Identifier: The GOG Foundation, Inc.)
  • ENGOT-ov81 (Other Identifier: ENGOT)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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