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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06072781




Registration number
NCT06072781
Ethics application status
Date submitted
2/10/2023
Date registered
10/10/2023
Date last updated
30/08/2024

Titles & IDs
Public title
A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer
Scientific 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)
Secondary ID [1] 0 0
GOG-3097
Secondary ID [2] 0 0
VS-6766-301
Universal Trial Number (UTN)
Trial acronym
RAMP 301
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Low Grade Serous Ovarian Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - avutometinib
Treatment: Drugs - Defactinib
Treatment: Drugs - Pegylated liposomal doxorubicin
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Topotecan
Treatment: Drugs - Letrozole
Treatment: Drugs - Anastrozole

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.

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.


Treatment: Drugs: avutometinib
Avutometinib: administered orally

Treatment: Drugs: Defactinib
Defactinib: administered orally

Treatment: Drugs: Pegylated liposomal doxorubicin
administered intravenously

Treatment: Drugs: Paclitaxel
administered intravenously

Treatment: Drugs: Topotecan
administered intravenously

Treatment: Drugs: Letrozole
administered orally

Treatment: Drugs: Anastrozole
administered orally

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) per blinded independent central review (BICR)
Timepoint [1] 0 0
Up to 24 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Progression Free Survival (PFS) per investigator assessment
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Objective response rate (ORR)
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
Duration of Response (DOR)
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Disease Control Rate (DCR)
Timepoint [5] 0 0
6 months
Secondary outcome [6] 0 0
Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)
Timepoint [6] 0 0
25 months
Secondary outcome [7] 0 0
Area under the plasma concentration-time curve (AUC) of avutometinib, defactinib and relative metabolites
Timepoint [7] 0 0
5 months
Secondary outcome [8] 0 0
Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites
Timepoint [8] 0 0
5 months
Secondary outcome [9] 0 0
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).
Timepoint [9] 0 0
24 months
Secondary outcome [10] 0 0
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).
Timepoint [10] 0 0
24 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 0 0
Icon Cancer Centre Wesley - Auchenflower
Recruitment hospital [3] 0 0
Cancer Research South Australia - Adelaide
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4066 - Auchenflower
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Oregon
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Italy
State/province [22] 0 0
Milan
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Scotland
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Edinburgh
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Manchester
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Verastem, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
GOG Foundation
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Rachel Grisham, MD
Address 0 0
GOG Foundation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Verastem Call Center
Address 0 0
Country 0 0
Phone 0 0
781-292-4204
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.