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New treatment option for Endometrioid Cancer
Official title A Phase 2 Study of Avutometinib (VS-6766) Plus Defactinib
ClinicalTrials.gov ID: NCT05512208
What this study is testing
What is Avutometinib (VS-6766) + defactinib?
Avutometinib (VS-6766) + defactinib is an investigational medicine, given as a twice-daily pill taken by mouth, being studied as a potential treatment for endometrioid cancer.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- The purpose of this research is to test the effectiveness and safety of the study drugs (VS-6766 and defactinib), and see what effects (good and bad) these drugs have on the patients with endometrioid cancer, mucinous ovarian cancer, high-grade serous ovarian cancer, or solid gynecological cancer.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 to 99, women only
You may be able to join if
- Female people ≥ 18 years of age.
- Histologically proven gynecological cancers (endometrioid, MOC, HGSOC and solid gynecological cancers) with mutated RAS, BRAF (type I, II, and/or...
- Mutational status will be taken from the previous next-gen sequencing (NGS) or molecular testing results and reviewed by the Principal Investigator...
- Adequate pathology material (as defined in the lab manual) must be available prior to treatment assignment to be used for confirmation.
- Tumor with known RAS mutation, BRAF (type I, II, and/or III) mutation, NF-1 and/or RAS activation status determined from previous NGS or molecular...
You likely can't join if
- Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
- Prior MEKi or RAFi exposure.
- Low grade serous ovarian cancer (LGSOC).
- History of prior malignancy with recurrence \<3 years from the time of enrollment. people with basal cell carcinoma of the skin, superficial bladder...
- people who are deemed in the opinion of their treating physician to be appropriate candidates for a debulking surgery. These people should...
- Major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 1 week (7...
See the full eligibility criteria
Who can join
- Female people ≥ 18 years of age.
- Histologically proven gynecological cancers (endometrioid, MOC, HGSOC and solid gynecological cancers) with mutated RAS, BRAF (type I, II, and/or III), NF-1 loss of function, and/or RAS activation.
- Mutational status will be taken from the previous next-gen sequencing (NGS) or molecular testing results and reviewed by the Principal Investigator prior to the start of treatment.
- Adequate pathology material (as defined in the lab manual) must be available prior to treatment assignment to be used for confirmation.
- Tumor with known RAS mutation, BRAF (type I, II, and/or III) mutation, NF-1 and/or RAS activation status determined from previous NGS or molecular testing. Adequate archival tumor tissue less than 5 years old or fresh...
- Progression (radiographic or clinical) or recurrence of gynecological cancer after at least one prior systemic therapy for metastatic disease. Below are additional prior treatments that are allowed once the requirement...
- Measurable disease according to RECIST 1.1.
- An Eastern Cooperative Group (ECOG) performance status ≤ 2.
- Must have adequate organ function defined by the following laboratory parameters:
- Adequate hematologic function including: hemoglobin [Hb] ≥9.0 g/dL; platelets ≥100,000/mm3; and absolute neutrophil count [ANC] ≥1500/mm3). If a red blood cell transfusion has been administered the Hb must remain stable...
- Adequate hepatic function: (i) total bilirubin ≤1.5 × upper limit of normal [ULN] for the institution; people with Gilbert syndrome may enroll if total bilirubin is \<3.0 mg/dL (51 μmole/L) upon discussion with the...
- 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.
- International normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x ULN in the absence of anticoagulation or therapeutic levels in the presence of anticoagulation.
- Albumin ≥3.0 g/dL (451 μmole/L).
- Creatine phosphokinase (CPK) ≤2.5 x ULN.
- Adequate cardiac function with left ventricular ejection fraction ≥ 55% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan.
- Baseline QTc interval \< 460 ms (average of triplicate readings) (CTCAE Grade1) using Fredericia's QT correction formula. NOTE: This criterion does not apply to people with a right or left bundle branch block.
- Adequate recovery from toxicities related to prior treatments to at least Grade 1 by CTCAE v 5.0
- Exceptions include alopecia and peripheral neuropathy Grade ≤2. people with other toxicities that are stable on supportive therapy may be allowed to participate with prior approval by the Sponsor.
- Females with reproductive potential and their male partners agree to use highly effective method of contraceptive (per recommendations in Section 13.4) during the trial and for 1 month following the last dose of...
What rules you out
- Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
- Prior MEKi or RAFi exposure.
- Low grade serous ovarian cancer (LGSOC).
- History of prior malignancy with recurrence \<3 years from the time of enrollment. people with basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, and in situ cervical...
- people who are deemed in the opinion of their treating physician to be appropriate candidates for a debulking surgery. These people should preferentially receive surgery prior to consideration of trial therapy.
- Major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 1 week (7 days) of the first dose of study therapy.
- Treatment with warfarin. people on warfarin for DVT/PE can be converted to low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs).
- Exposure to strong CYP2C9 and CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy. See Table 14 and Table 15 for representative lists of CYP inhibitors and inducers. For...
- Exposure to P-glycoprotein (P-gp) inhibitors or inducers within 14 days prior to the first dose and during the course of the study. See Table 16 for a representative list of P-gp inhibitors and inducers.
- Symptomatic brain metastases requiring steroids or other interventions. These metastases may manifest as altered mental status, persistent headaches, persistent nausea, focal weakness or numbness, and seizures. people...
- Known SARS-Cov2 infection (clinical symptoms) ≤28 days prior to first dose of study therapy.
- Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection that is active and/or requires therapy.
- Active skin disorder that has required systemic therapy within the past year.
- History of rhabdomyolysis.
- Concurrent ocular disorders:
- people with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes.
- Subject 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...
- people 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.
- Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), myocardial infarction within the last 6 months, unstable arrhythmias, unstable angina, or severe...
- people with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease.
- people with a history of hypersensitivity to any of the active or inactive Avutometinib ingredients (hydroxypropylmethylcellulose, mannitol, magnesium stearate) of the investigational product.
- Female people who are pregnant or breastfeeding.
- Any other medical condition (e.g. cardiac, gastrointestinal, pulmonary, psychiatric, neurological, genetic, etc.) that in the opinion of the investigator would place the subject at unacceptably high risk for toxicity.
The study team makes the final eligibility decision.
Where it's taking place
- Orlando, Florida, United States
- New Orleans, Louisiana, United States
- Albuquerque, New Mexico, United States
- Oklahoma City, Oklahoma, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling female, 18 years to 99 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Orlando, Florida, United States; New Orleans, Louisiana, United States; Albuquerque, New Mexico, United States; Oklahoma City, Oklahoma, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.