A Study of Avutometinib and Defactinib in People With Thyroid Cancer
Phase II of Avutometinib (VS-6766) and Defactinib In RAF Dimer-Driven RAI-Refractory Differentiated and Anaplastic Thyroid Cancer Patients
2 other identifiers
interventional
30
1 country
7
Brief Summary
The researchers are doing this study to find out if the combination of avutometinib and defactinib is an effective treatment for RAF dimer-driven radioiodine-refractory differentiated thyroid cancer or anaplastic thyroid cancer. The researchers will also test whether avutometinib and defactinib is a safe treatment that causes few or mild side effects.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Aug 2023
Typical duration for phase_2
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 16, 2023
CompletedFirst Submitted
Initial submission to the registry
August 17, 2023
CompletedFirst Posted
Study publicly available on registry
August 23, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 16, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 16, 2027
March 27, 2026
March 1, 2026
4 years
August 17, 2023
March 25, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
overall response rate (ORR) cohort A
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
up to 2 years
overall response rate (ORR) cohort B
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
up to 2 years
Study Arms (2)
Radioiodine-refractory (RAIR), recurrent and/or metastatic differentiated thyroid cancer (DTC)
EXPERIMENTALPatients will be treated with avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily, both 3 weeks on/1 week off.
Anaplastic thyroid cancer (ATC)
EXPERIMENTALPatients will be treated with avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily, both 3 weeks on/1 week off.
Interventions
Defactinib 200 mg twice daily 3 weeks on/1 week off
Avutometinib 3.2 mg twice weekly 3 weeks on/1 week off
Eligibility Criteria
You may qualify if:
- Cohort A will enroll RAIR, R/M DTC patients with RAF dimer-driven disease.
- Cohort B will enroll ATC patients with RAF dimer-driven disease.
- Cohort A only: Patients must have pathologically or cytologically confirmed differentiated thyroid cancer of follicular origin (including papillary thyroid carcinoma, follicular thyroid carcinoma, hurthle cell carcinomas, poorly differentiated thyroid carcinoma and their respective variants).
- Cohort B only: Patients must have anaplastic thyroid carcinoma.
- Confirmation in a CLIA certified laboratory that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastases) possess at least one of the following genetic alterations: RAS mutation, NF1 mutation, RET rearrangement, NTRK rearrangement, ALK rearrangement, Class 2 or 3 BRAF alterations (non-V600E/K mutations or rearrangements).
- Cohort A only: Evidence of progressive disease (e.g. presence of new or growing lesion(s) on radiologic imaging and/or new or worsening tumor-related symptoms) within 14 months of study enrollment.
- Cohort A only: Patients must have recurrent or metastatic disease not amenable to curative surgery or radiation.
- Patients with any number of prior therapies will be eligible.
- Patients must have RECIST v1.1 measurable disease.
- Age ≥ 18 years.
- ECOG performance status of 0 or 1.
- For Cohort A only: Patients must have not had recent treatment for thyroid cancer as defined as:
- No prior RAI therapy is allowed \<6 months prior to initiation of therapy on this protocol. A diagnostic study using \<10 mCi of RAI is not considered RAI therapy
- No external beam radiation therapy \<1 weeks prior to initiation of therapy on this protocol.
- No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed \<4 weeks prior to the initiation of therapy on this protocol
- +24 more criteria
You may not qualify if:
- Symptomatic untreated brain or leptomeningeal metastases Note: Patients with asymptomatic or treated brain or leptomeningeal metastases are allowed. Participants with symptomatic brain or leptomeningeal metastases after surgical and/org radiation therapy may be allowed with Principal Investigator approval.
- Prior therapy with a MEK 1/2 inhibitor or an inhibitor that targets Class II/Class III BRAF alterations or a FAK inhibitor (with the exception of patients who received these therapies for a defined period of time to enhance radioiodine activity).
- Patient who have had systemic investigational anti-cancer therapy within 4 weeks of the first dose of study therapy.
- Major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or radiotherapy within 1 week of the first dose of study drug.
- Treatment with warfarin. Patients on warfarin for deep vein thrombosis/pulmonary embolism should be converted to low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs).
- Concomitant use of strong inhibitors and inducers of CYP3A4 (see Appendix 1 in Section 18). Patients should refrain from consumption of grapefruit, grapefruit juice and St. John's Wort, and other medications (with or without prescriptions), supplements, herbal remedies or foods that are strong inhibitors or inducers of CYP3A4 during treatment
- Concomitant use of strong CYP2C9 inhibtors or inducers. For additional guidance see https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers
- Concomitant use of strong P-glycoprotein(P-gp) inhibitors or inducers. For additional guidance see https://www.uptodate.com/contents/image/print?imageKey=EM%2F73326\&topicKey=HEME%2F1370\&source=outlinelink
- Patients with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes.
- Patients with a history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, such as an intraocular pressure \> 21 mmHg
- Treatment-refractory hypertension defined as a blood pressure of systolic \>140 mmHg and/or diastolic \>90 mmHg which cannot be controlled by anti-hypertensive therapy.
- Patients with active hepatitis B infection (HBV surface antigen positive).
- Subject is known to be positive for Human Immunodeficiency Virus (HIV) or active Hepatitis C Virus (HCV). Testing for HIV or Hepatitis C prior to initiation of the study drug is not required. If a patient has a known history of treated HCV, then a viral load is required to confirm clearance of infection.
- Known severe acute respiratory syndrome coronavirus 2 SARS-Cov2 infection (clinical symptoms) ≤28 days prior to first dose of study therapy.
- History of rhabdomyolysis.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Verastem, Inc.collaborator
- Memorial Sloan Kettering Cancer Centerlead
Study Sites (7)
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Cancer Center Suffolk - Commack (Limited Protocol Activities)
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Rockville Centre, New York, 11553, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alan Ho, MD, PhD
Memorial Sloan Kettering Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 17, 2023
First Posted
August 23, 2023
Study Start
August 16, 2023
Primary Completion (Estimated)
August 16, 2027
Study Completion (Estimated)
August 16, 2027
Last Updated
March 27, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.