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

Primary Purpose

Low Grade Serous Ovarian Cancer

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
avutometinib
Defactinib
Pegylated liposomal doxorubicin
Paclitaxel
Topotecan
Letrozole
Anastrozole
Sponsored by
Verastem, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Low Grade Serous Ovarian Cancer focused on measuring Low Grade Serous Ovarian Cancer, KRAS, KRAS wt, KRAS mt

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Patients may be eligible for inclusion in the study if they meet the following criteria: Histologically proven LGSOC (ovarian, fallopian, peritoneal) Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease. Measurable disease according to RECIST v1.1. An Eastern Cooperative Group (ECOG) performance status ≤ 1. Adequate organ function Adequate recovery from toxicities related to prior treatments. For patients with reproductive potential, Agreement to use highly effective method of contraceptive. 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: Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy. Co-existing high-grade ovarian cancer or another histology. Prior treatment with avutometinib, defactinib, or other FAK inhibitors. History of prior malignancy with recurrence <3 years from the time of enrollment. Major surgery within 4 weeks. Symptomatic brain metastases or spinal cord compression. An active skin disorder that has required systemic therapy within one year of signing informed consent. History of medically significant rhabdomyolysis. For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor. Symptomatic bowel obstruction within 3 months. Concurrent ocular disorders. Concurrent heart disease or severe obstructive pulmonary disease. Subjects with the inability to swallow oral medications. Active, uncontrolled infection (bacterial, viral, or fungal) requiring systemic therapy.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    avutometinib + defactinib

    Investigator Choice of Treatment (ICT)

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Progression Free Survival (PFS) per blinded independent central review (BICR)
    Confirmed overall response rate per RECIST 1.1 per blinded independent central review (BICR)

    Secondary Outcome Measures

    Overall Survival (OS)
    From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause
    Progression Free Survival (PFS) per investigator assessment
    From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
    Objective response rate (ORR)
    From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
    Duration of Response (DOR)
    From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
    Disease Control Rate (DCR)
    CR+PR+Stable disease
    Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)
    Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale
    Area under the plasma concentration-time curve (AUC) of avutometinib, defactinib and relative metabolites
    Area under plasma Concentration (AUC) 0 to t
    Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites
    maximum plasma concentration
    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).
    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.
    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).
    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.

    Full Information

    First Posted
    October 2, 2023
    Last Updated
    October 12, 2023
    Sponsor
    Verastem, Inc.
    Collaborators
    GOG Foundation, European Network of Gynaecological Oncological Trial Groups (ENGOT)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06072781
    Brief Title
    A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer
    Acronym
    RAMP 301
    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)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 15, 2023 (Anticipated)
    Primary Completion Date
    October 15, 2028 (Anticipated)
    Study Completion Date
    February 9, 2031 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Verastem, Inc.
    Collaborators
    GOG Foundation, European Network of Gynaecological Oncological Trial Groups (ENGOT)

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief 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 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)

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Low Grade Serous Ovarian Cancer
    Keywords
    Low Grade Serous Ovarian Cancer, KRAS, KRAS wt, KRAS mt

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Crossover Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    270 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    avutometinib + defactinib
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Investigator Choice of Treatment (ICT)
    Arm Type
    Active Comparator
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    avutometinib
    Other Intervention Name(s)
    avutometinib (VS-6766)
    Intervention Description
    Avutometinib: administered orally
    Intervention Type
    Drug
    Intervention Name(s)
    Defactinib
    Other Intervention Name(s)
    defactinib (VS-6063)
    Intervention Description
    Defactinib: administered orally
    Intervention Type
    Drug
    Intervention Name(s)
    Pegylated liposomal doxorubicin
    Other Intervention Name(s)
    Caelyx, Doxil, Lipodox
    Intervention Description
    administered intravenously
    Intervention Type
    Drug
    Intervention Name(s)
    Paclitaxel
    Other Intervention Name(s)
    Nov-Onxol, Onxol, Navaplus, Taxol
    Intervention Description
    administered intravenously
    Intervention Type
    Drug
    Intervention Name(s)
    Topotecan
    Other Intervention Name(s)
    Hycamtin
    Intervention Description
    administered intravenously
    Intervention Type
    Drug
    Intervention Name(s)
    Letrozole
    Other Intervention Name(s)
    Femara
    Intervention Description
    administered orally
    Intervention Type
    Drug
    Intervention Name(s)
    Anastrozole
    Other Intervention Name(s)
    Arimidex
    Intervention Description
    administered orally
    Primary Outcome Measure Information:
    Title
    Progression Free Survival (PFS) per blinded independent central review (BICR)
    Description
    Confirmed overall response rate per RECIST 1.1 per blinded independent central review (BICR)
    Time Frame
    Up to 24 months
    Secondary Outcome Measure Information:
    Title
    Overall Survival (OS)
    Description
    From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause
    Time Frame
    Up to 5 years
    Title
    Progression Free Survival (PFS) per investigator assessment
    Description
    From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
    Time Frame
    24 months
    Title
    Objective response rate (ORR)
    Description
    From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
    Time Frame
    12 months
    Title
    Duration of Response (DOR)
    Description
    From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
    Time Frame
    12 months
    Title
    Disease Control Rate (DCR)
    Description
    CR+PR+Stable disease
    Time Frame
    6 months
    Title
    Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)
    Description
    Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale
    Time Frame
    25 months
    Title
    Area under the plasma concentration-time curve (AUC) of avutometinib, defactinib and relative metabolites
    Description
    Area under plasma Concentration (AUC) 0 to t
    Time Frame
    5 months
    Title
    Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites
    Description
    maximum plasma concentration
    Time Frame
    5 months
    Title
    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).
    Description
    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.
    Time Frame
    24 months
    Title
    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).
    Description
    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.
    Time Frame
    24 months

    10. Eligibility

    Sex
    Female
    Gender Based
    Yes
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients may be eligible for inclusion in the study if they meet the following criteria: Histologically proven LGSOC (ovarian, fallopian, peritoneal) Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease. Measurable disease according to RECIST v1.1. An Eastern Cooperative Group (ECOG) performance status ≤ 1. Adequate organ function Adequate recovery from toxicities related to prior treatments. For patients with reproductive potential, Agreement to use highly effective method of contraceptive. 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: Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy. Co-existing high-grade ovarian cancer or another histology. Prior treatment with avutometinib, defactinib, or other FAK inhibitors. History of prior malignancy with recurrence <3 years from the time of enrollment. Major surgery within 4 weeks. Symptomatic brain metastases or spinal cord compression. An active skin disorder that has required systemic therapy within one year of signing informed consent. History of medically significant rhabdomyolysis. For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor. Symptomatic bowel obstruction within 3 months. Concurrent ocular disorders. Concurrent heart disease or severe obstructive pulmonary disease. Subjects with the inability to swallow oral medications. Active, uncontrolled infection (bacterial, viral, or fungal) requiring systemic therapy.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Verastem Call Center
    Phone
    781-292-4204
    Email
    clinicaltrials@verastem.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Rachel Grisham, MD
    Organizational Affiliation
    GOG Foundation
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Susana Banerjee, MBBS, MA, PhD
    Organizational Affiliation
    European Network of Gynecological Oncological Trial Groups (ENGOT)
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    MD Verastem
    Organizational Affiliation
    Verastem, Inc.
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

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

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