Trial Title:
A Study of Avutometinib, Defactinib, and Letrozole in People With Low-Grade Serous Ovarian Cancer
NCT ID:
NCT06394804
Condition:
Low-Grade Serous Ovarian Cancer
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Letrozole
Conditions: Keywords:
Avutometinib
Defactinib
Letrozole
24-014
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
Description:
Starting Dose 3.2 mg BIW for 3 of 4 weeks, Dose -1, 2.4 mg BIW for 3 of 4 weeks
Arm group label:
Avutometinib, Defactinib, and Letrozole
Other name:
VS-6766
Intervention type:
Drug
Intervention name:
Defactinib
Description:
Starting Dose 200 mg BID for 3 of 4 weeks, Dose -1, 200 mg QD for 3 of 4 weeks
Arm group label:
Avutometinib, Defactinib, and Letrozole
Other name:
VS-6063
Intervention type:
Drug
Intervention name:
Letrozole
Description:
2.5 mg PO daily
Arm group label:
Avutometinib, Defactinib, and Letrozole
Summary:
The researchers are doing this study to find out whether the combination of avutometinib,
defactinib, and letrozole is an effective treatment for people with low-grade serous
ovarian cancer (LGSOC). The researchers will also look at the safety of this combination.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Female patients ≥ 18 years of age
- Histologically-confirmed LGSOC (ovarian, peritoneal) by tissue biopsy read by
pathology at study institution. NOTE: Patients with a prior history of serous
borderline tumors without prior systemic (cytotoxic or hormonal) treatment but a new
diagnosis of low-grade serous ovarian cancer are eligible.
- Determination that the patient is not a primary surgical candidate by a gynecologic
oncologist surgeon; or has undergone an attempted primary debulking with residual
RECIST measurable disease.
- Measurable disease according to RECIST 1.1. Measurable disease is defined as at
least one lesion that can be accurately measured in at least one dimension. Each
lesion must be ≥10mm when measured by CT or MRI. Lymph nodes must be ≥15mm by short
axis when measured by CT or MRI.
- An Eastern Cooperative Group (ECOG) performance status of ≤1. Patients with an ECOG
performance status of 2 are permitted on trial if this is deemed to be secondary to
cancer but not to other comorbidities.
- 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 anti-HCV 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.
- 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, unless surgical menopause is conferred. Women of child-bearing
potential must have a negative pregnancy test within 14 days prior to commencement
of study treatment. 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
≥ 50% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan.
- Baseline QTc interval < 460 ms (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.
- Adequate organ function, defined by the following parameters:
°Adequate hematologic function
- Hemoglobin [Hb] ≥ 9.0 g/dL. If a red blood cell transfusion has been administered
the Hb must remain stable and ≥ 9.0 g/dL for at least 1 week prior to first dose of
study intervention.
- Platelets ≥ 100,000/mm^3
- Absolute neutrophil count [ANC] ≥ 1000/mm^3
°Adequate hepatic function:
- Total bilirubin ≤1.5 × upper limit of normal [ULN] for the institution; patients
with Gilbert syndrome may enroll if total bilirubin is <3.0mg/dL (51 μmole/L) upon
discussion with MSK PI.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (or
<5 xULN in patients with liver metastases).
- Adequate renal function with creatinine clearance rate of ≥50 mL/min as
calculated by the Cockcroft-Gault formula or serum creatinine of ≤ 1.5 x ULN.
- Creatine phosphokinase (CPK) ≤2.5 x ULN.
Exclusion Criteria:
- Patients who are deemed in the opinion of their treating physician to be appropriate
candidates for a primary debulking surgery are not eligible for this trial, unless
measurable disease remains after a primary cytoreductive surgery.
- Prior systemic anti-cancer therapy for LGSOC or serous borderline disease.
- Major surgery within 4 weeks, minor surgery within 2 weeks, or palliative
radiotherapy within 1 week of the first dose of study intervention. Open and close
laparotomy and/or laparoscopy will be considered minor surgery.
- 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).
- Patients with the inability to swallow oral medications or impaired gastrointestinal
absorption due to gastrectomy or drainage PEG tube. Patients with diagnosis of bowel
obstruction <3 months from study enrollment will be excluded.
- Symptomatic brain metastases requiring steroids or other interventions. Patients
with new asymptomatic CNS metastases detected during the screening period must
receive radiation therapy and/or surgery for CNS metastases. Following treatment,
these patients may then be eligible if all other criteria are met.
- 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 (Avutometinib,
defactinib) or inactive (hydroxypropylmethylcellulose, mannitol, magnesium stearate)
ingredients of the investigational product.
- Female patients who are breastfeeding.
- 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 (Appendix 1), including:
- strong CYP3A4 inhibitors or inducers, due to potential drug-drug interactions
with both Avutometinib 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.
Gender:
Female
Gender based:
Yes
Gender description:
Ovarian 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 Westchester (Limited Protocol Activities)
Address:
City:
Harrison
Zip:
10604
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:
Chrisann Kyi, MD
Phone:
646-888-4221
Investigator:
Last name:
Rachel Grisham, MD
Email:
Principal Investigator
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
Start date:
April 29, 2024
Completion date:
April 2027
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/NCT06394804
http://www.mskcc.org/mskcc/html/44.cfm
