A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer (RAMP 301)
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| ClinicalTrials.gov Identifier: NCT06072781 |
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Recruitment Status :
Recruiting
First Posted : October 10, 2023
Last Update Posted : May 9, 2024
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Sponsor:
Verastem, Inc.
Collaborators:
GOG Foundation
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Information provided by (Responsible Party):
Verastem, Inc.
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Low Grade Serous Ovarian Cancer | Drug: avutometinib Drug: Defactinib Drug: Pegylated liposomal doxorubicin Drug: Paclitaxel Drug: Topotecan Drug: Letrozole Drug: Anastrozole | Phase 3 |
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 (Clinical Trial) |
| Estimated Enrollment : | 270 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | March 18, 2024 |
| Estimated Primary Completion Date : | October 15, 2028 |
| Estimated Study Completion Date : | February 9, 2031 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Ovarian cancer
MedlinePlus related topics:
Ovarian Cancer
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: avutometinib
Avutometinib: administered orally
Other Name: avutometinib (VS-6766) Drug: Defactinib Defactinib: administered orally
Other Name: defactinib (VS-6063) |
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Active Comparator: Investigator Choice of Treatment (ICT)
Patients will receive one of the following therapies as determined by the Investigator:
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Drug: Pegylated liposomal doxorubicin
administered intravenously
Other Name: Caelyx, Doxil, Lipodox Drug: Paclitaxel administered intravenously
Other Name: Nov-Onxol, Onxol, Navaplus, Taxol Drug: Topotecan administered intravenously
Other Name: Hycamtin Drug: Letrozole administered orally
Other Name: Femara Drug: Anastrozole administered orally
Other Name: Arimidex |
Primary Outcome Measures :
- 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)
Secondary Outcome Measures :
- 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
- 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
- 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
- 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
- Disease Control Rate (DCR) [ Time Frame: 6 months ]CR+PR+Stable disease
- 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
- 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
- Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites [ Time Frame: 5 months ]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). [ 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.
- 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.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Gender Based Eligibility: | Yes |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06072781
Contacts
| Contact: Verastem Call Center | 781-292-4204 | clinicaltrials@verastem.com |
Locations
Show 21 study locations
Sponsors and Collaborators
Verastem, Inc.
GOG Foundation
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Investigators
| Principal Investigator: | Rachel Grisham, MD | GOG Foundation | |
| Principal Investigator: | Susana Banerjee, MBBS, MA, PhD | European Network of Gynecological Oncological Trial Groups (ENGOT) | |
| Study Director: | MD Verastem | Verastem, Inc. |
| Responsible Party: | Verastem, Inc. |
| ClinicalTrials.gov Identifier: | NCT06072781 |
| Other Study ID Numbers: |
VS-6766-301 GOG-3097 ( Other Identifier: The GOG Foundation, Inc. ) ENGOT-ov81 ( Other Identifier: ENGOT ) |
| First Posted: | October 10, 2023 Key Record Dates |
| Last Update Posted: | May 9, 2024 |
| Last Verified: | May 2024 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Verastem, Inc.:
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Low Grade Serous Ovarian Cancer KRAS KRAS wt KRAS mt |
Additional relevant MeSH terms:
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Ovarian Neoplasms Carcinoma, Ovarian Epithelial Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Neoplasms, Female Urogenital Neoplasms Genital Diseases Endocrine System Diseases |
Gonadal Disorders Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Paclitaxel Doxorubicin Liposomal doxorubicin Letrozole Topotecan Anastrozole Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators |