Trial Title:
A Study of Avutometinib (VS-6766) and Defactinib in People with Mesonephric Gynecologic Cancer
NCT ID:
NCT05787561
Condition:
Mesonephric Gynecologic Cancer
Conditions: Keywords:
Avutometinib (VS-6766)
Defactinib
22-392
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Avutometinib (VS-6766)
Description:
3.2 mg PO, twice weekly
Arm group label:
Avutometinib (VS-6766) and Defactinib
Intervention type:
Drug
Intervention name:
Defactinib
Description:
200 mg PO BID for 3 weeks, followed by a 1 week rest period, in each 4-week (28 day)
cycle.
Arm group label:
Avutometinib (VS-6766) and Defactinib
Summary:
This study will test if Avutometinib (VS-6766) in combination with Defactinib is an
effective treatment for advanced or recurrent mesonephric gynecologic cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Female patients ≥ 18 years of age
- Histologic confirmation of Gynecologic Mesonephric or Mesonephric-like cancer (GMC).
Patients with mixed histology are eligible if the disease is deemed by the treating
physician to be driven by the GMC component.
- Measurable disease according to RECIST 1.1
- Patients must have persistent (disease that is metastatic at presentation or remains
present following first-line therapy) or recurrent disease (disease that has come
back or progressed following prior surgery or treatment)
- Patients with metastatic or recurrent disease do not require any prior systemic
therapy prior to enrollment. Patients may have received unlimited lines of prior
systemic therapy.
- Patients with treated brain metastases are eligible if follow-up brain imaging after
CNS-directed therapy shows no evidence of progression. Patients with asymptomatic
brain metastases that do not require intervention are also eligible.
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load.
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial.
- Resolution of all toxicities of prior therapy or surgical procedures to baseline or
Grade 1 (except for hypothyroidism requiring medication, and alopecia, which must
have resolved to Grade ≤2).
- Female patients with reproductive potential agree to use highly effective method of
contraceptive during the trial and for 1 month following the last dose of study
intervention. Hormonal forms of contraception are not recommended in this study.
Non-hormonal methods of highly effective contraception include:
- intrauterine device (IUD)
- bilateral tubal occlusion
- vasectomized partner
- sexual abstinence
- Patients must have adequate cardiac function with left ventricular ejection
fraction ≥ 55% by echocardiography (ECHO)
- Baseline QTc interval < 460 ms (average of triplicate readings) (Common
Terminology Criteria for Adverse Events [CTCAE] Grade 1) using Fredericia's QT
correction formula. NOTE: This criterion does not apply to patients with a
right or left bundle branch block.
- Must have adequate organ function defined by the following laboratory
parameters:
- Total Bilirubin: ≤ 1.5 x institutional upper limit of normal (ULN)
(patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN
may be enrolled)
- AST(SGOT)/ALT(SGPT): ≤3 × institutional ULN
- Adequate renal function defined as either:
Creatinine clearance (CrCL) or estimated Glomerular filtration rate (eGFR) of ≥50 mL/min
estimated using either the Cockcroft-Gault equation, the Modification of Diet in Renal
Disease Study, or as reported in the comprehensive metabolic panel/basic metabolic panel
(eGFR).
Or:
Serum Creatinine ≤ 1.5 x ULN
- Creatine phosphokinase (CPK) ≤ 2.5 x ULN.
- Adequate hematologic function including: hemoglobin [Hb] ≥ 9.0 g/dL; platelets ≥
100,000/mm^3; and absolute neutrophil count [ANC] ≥ 1000/mm^3
Exclusion Criteria:
- Patients with newly diagnosed localized disease should be treated as per standard of
care and are not eligible for this study. Patients who are candidates for
potentially curative surgery or radiation are not eligible for this trial.
- Systemic anti-cancer therapy (other than endocrine therapy) within 4 weeks, 1 cycle,
or 5 half-lives (whichever is shortest) of the first dose of study intervention;
Endocrine therapy within 1 week of the first dose of study intervention.
- Major surgery within 4 weeks , minor surgery within 2 weeks, or palliative
radiotherapy within 1 week of the first dose of study intervention.
- Treatment with warfarin. Patients on warfarin for deep vein thrombosis/pulmonary
embolism can be converted to low-molecular-weight heparin or direct oral
anticoagulants (DOACs).
- Prior treatment with a MEK or RAF or FAK inhibitor
- Patients with the inability to swallow oral medications or impaired gastrointestinal
absorption due to gastrectomy or drainage PEG tube
- Patients with history of retinal pathology or evidence of visible retinal pathology
that is considered a risk factor for RVO, intraocular pressure > 21 mm Hg as
measured by tonometry, or other significant ocular pathology, such as anatomical
abnormalities that increase the risk for RVO
- Patients with a history of corneal erosion (instability of corneal epithelium),
corneal degeneration, active or recurrent keratitis, and other forms of serious
ocular surface inflammatory conditions.
- History of rhabdomyolysis
- Patients with a history of hypersensitivity to any of the active or inactive
avutometinib (VS-6766) and defactinib ingredients (hydroxypropylmethylcellulose,
mannitol, magnesium stearate) of the investigational product.
- Any other medical condition (e.g., cardiac, gastrointestinal, pulmonary,
psychiatric, neurological, genetic, etc.) that in the opinion of the Investigator
would places the patient at unacceptably high risk for toxicity.
- Exposure to medications (with or without prescriptions), supplements, herbal
remedies, or foods with potential for drug-drug interactions with study
interventions within 14 days prior to the first dose of study intervention and
during the course of therapy, including:
- strong CYP3A4 inhibitors or inducers, due to potential drug-drug interactions
with both avutometinib (VS-6766) and defactinib.
- strong CYP2C9 inhibitors or inducers, due to potential drug-drug interactions
with defactinib.
- P-glycoprotein (P-gp) inhibitors or inducers, due to potential drug-drug
interactions with defactinib.
- strong breast cancer resistance protein (BCRP) inhibitors or inducers, due to
potential drug-drug interactions with avutometinib and defactinib.
Gender:
Female
Gender based:
Yes
Gender description:
Mesonephric Gynecologic Cancer
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rachel Grisham, MD
Phone:
646-888-4653
Facility:
Name:
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rachel Grisham, MD
Phone:
646-888-4653
Facility:
Name:
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rachel Grisham, MD
Phone:
646-888-4653
Facility:
Name:
Memorial Sloan Kettering Suffolk -Commack (Limited Protocol Activities)
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rachel Grisham, MD
Phone:
646-888-4653
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rachel Grisham, MD
Phone:
646-888-4653
Contact backup:
Last name:
Carol Aghajanian, MD
Phone:
646-888-4217
Contact backup:
Last name:
Rachel Grisham, MD
Facility:
Name:
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rachel Grisham, MD
Phone:
646-888-4653
Facility:
Name:
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Address:
City:
West Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rachel Grisham, MD
Phone:
646-888-4653
Start date:
March 15, 2023
Completion date:
March 2025
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Collaborator:
Agency:
Verastem, Inc.
Agency class:
Industry
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05787561
http://www.mskcc.org/mskcc/html/44.cfm
