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Endometrioid CancerPhase 2DURAFAKNCT05512208

A Phase 2 Study of Avutometinib (VS-6766) Plus Defactinib

A Phase 2 study testing Avutometinib (VS-6766) + defactinib in people with Endometrioid Cancer and Mucinous Ovarian Cancer, run by University of Oklahoma at 4 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 99 years, women only
What is being tested?
Avutometinib (VS-6766) + defactinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
4 sitesUnited States
Study dates
6 Feb 2023to Dec 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Female subjects ≥ 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 biopsy tissue samples (as defined in the lab manual) must be available.
  • 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 of prior platinum therapy is satisfied.
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  • Prior systemic therapy for metastatic disease (FIGO stage II-IV) may consist of chemotherapy administered as single agent or a platinum or another chemotherapy doublet with or without bevacizumab, with or without maintenance therapy or radiation therapy; and/or hormonal therapy.
  • 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 and ≥9 g/dL for at least 1 week prior to first dose of study therapy.
  • Adequate hepatic function: (i) total bilirubin ≤1.5 × upper limit of normal [ULN] for the institution; subjects with Gilbert syndrome may enroll if total bilirubin is <3.0 mg/dL (51 μmole/L) upon discussion with the Principal Investigator (PI). (ii) alanine aminotransferase (ALT) and alanine aminotransferase (AST) ≤2.5 × ULN (or <5x ULN in subjects 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.
  • 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 subjects 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. Subjects 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 Avutometinib for female patients.

Who cannot join

  • 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. Subjects with basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, and in situ cervical cancer that has undergone potentially curative therapy with no evidence of disease recurrence for ≥1 year since completion of the appropriate therapy may be included. Subjects with other malignancies associated with very low risk of metastasis or death may be included upon discussion with the PI.
  • Subjects who are deemed in the opinion of their treating physician to be appropriate candidates for a debulking surgery. These subjects 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.
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  • Treatment with warfarin. Subjects 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 additional guidance, see https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers.
  • 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. Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 2 weeks prior to first dose of study therapy, and are neurologically stable, with no evidence of interim progression. Subjects with new asymptomatic CNS metastases detected during the screening period must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these subjects may then be eligible if all other criteria are met.
  • 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:
  • Subjects 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 pathology, such as anatomical abnormalities that increase the risk for RVO.
  • Subjects 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 obstructive pulmonary disease.
  • Subjects with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease.
  • Subjects with a history of hypersensitivity to any of the active or inactive Avutometinib ingredients (hydroxypropylmethylcellulose, mannitol, magnesium stearate) of the investigational product.
  • Female subjects 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.

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

SCC IIT Office contact

4052718777

SCC-IIT-Office@ouhsc.edu

United States4 sites, 4 recruiting

  • University of New Mexico Comprehensive Cancer Center

    Albuquerque, New Mexico, 87131

    Carolyn Muller, MD, 505-925-0460, cmuller@salud.unm.edu

    Carolyn C Muller, MD

    Recruiting

  • Louisiana State University Medical Center New Orleans

    New Orleans, Louisiana, 70112

    Tara Castellano, MD, 504-568-4850, tcaste@lshuhsc.edu

    Tara Castellano, MD

    Recruiting

  • Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73117

    SCC IIT Office, 405-271-8777, SCC-IIT-Office@ouhsc.edu

    Recruiting

  • AdventHealth

    Orlando, Florida, 32804

    Robert Holloway, MD, 407-303-2422, Robert.Holloway.MD@AdventHealth.com

    Robert Holloway, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase 2 Study of VS-6766 (Dual RAF/MEK Inhibitor) Plus Defactinib (FAK Inhibitor) in Recurrent Gynecological Cancers (DURAFAK)

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.

Read the detailed description

This is a single-stage exploratory, Phase 2, multicenter, parallel cohort, open label study designed to evaluate efficacy and safety of VS-6766 + defactinib.

Enrolled study patients will receive the study drugs (VS-6766 and defactinib) to take orally based on the study procedures. Patients will follow the study procedures and attend all the study visits where various procedures including physical examinations, vitals, assessing the size of the patient's tumor, and examination of urine and blood may take place. Additional visits may be done to assess any other side effects a patient's experiences.

Being tested
Avutometinib (VS-6766) + defactinib
Keywords
Avutometinib, defactinib, VS-6766
Medical subject headings
Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Avutometinib (VS-6766) + defactinibDrug

    Avutometinib (VS-6766): will be administered at 3.2 mg orally twice a week Defactinib: will be administered at 200 mg orally twice a day (BID).

    Treatment will be for 3 weeks, followed by a 1-week rest period, in each 4-week (28 day) cycle.

Study groups in NCT05512208
Study groupRoleWhat they receive
Avutometinib (VS-6766) + DefactinibExperimentalAvutometinib (VS-6766): will be administered at 3.2 mg orally twice a week Defactinib: will be administered at 200 mg orally twice a day (BID).
Receives: Drug: Avutometinib (VS-6766) + defactinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Patients with objective response rate

    To evaluate the efficacy of Avutometinib (VS-6766) + defactinib in endometrioid, MOC, HGSOC and solid gynecological cancer patients with RAS/BRAF/NF1 mutations on confirmed overall response rate (ORR; partial response [PR] + complete response [CR] defined according to RECIST 1.1) as assessed by the investigator.

    Measured: 2 years

Secondary outcomes (5)

  1. Incidence of Adverse Events

    To characterize the safety and toxicity profile of Avutometinib (VS-6766) + defactinib combination measured by the incidence of Adverse events (AEs), serious AEs (SAEs), physical examinations, clinical laboratory values and tolerability (dose interruptions/reductions)

    Measured: 2 years

  2. Duration of Response

    Calculated for those subjects with a CR or PR as elapsed time from the first response to PD or death, as assessed by the investigator.

    Measured: 2 years

  3. Progression Free Survival

    elapsed time of first treatment to PD or death from any cause.

    Measured: 2 years

  4. Disease Control Rate

    CR+PR+ stable disease (SD) ≥8 weeks)

    Measured: 2 years

  5. Overall Survival

    elapsed time from the first treatment to death.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Aug 2022
  2. Study start6 Feb 2023
  3. Primary completionDec 2027 (estimated)
  4. Study completionDec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
A single-stage exploratory, Phase 2, multicenter, parallel cohort, open label study designed to evaluate efficacy and safety of VS-6766 + defactinib.
Masking
None (open label)
Enrolment
55 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05512208
Sponsor's protocol ID
OU-SCC-DURAFAK
Acronym
DURAFAK
Status last verified
Oct 2025
First submitted
9 Aug 2022
Last updated
22 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avutometinib (VS-6766) + defactinib in people with Endometrioid Cancer and Mucinous Ovarian Cancer, run by University of Oklahoma at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 22 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact SCC IIT Office (4052718777, SCC-IIT-Office@ouhsc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Patients with objective response rate (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05512208.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2025.

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