A Study of Avutometinib and Defactinib in People With Thyroid Cancer
ConditionThyroid Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMemorial Sloan Kettering Cancer Center
About this trial
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. Funding Source- FDA OOPD.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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). Patients with anaplastic thyroid cancer harboring a Class 1 BRAF alteration (V600E/K/D/R) also would be eligible if the patient has previously been treated with BRAF-targeted therapy (for example, dabrafenib plus trametinib, vemurafenib plus cobimetinib, encorafenib plus binimetinib, etc…).
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.
Disqualifiers
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). or patients who received MEK 1/2 inhibitor as part of treatment for BRAF V600E/K/D/R mutant anaplastic thyroid cancer).
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Avutometinib
DrugAvutometinib 3.2 mg twice weekly 3 weeks on/1 week off
Defactinib
DrugDefactinib 200 mg twice daily 3 weeks on/1 week off
Treatment groups
30 Participants
are divided into 2 treatment groupsGroup A: Radioiodine-refractory (RAIR), recurrent and/or metastatic differentiated thyroid cancer (DTC)Experimental treatment 2 interventions
Group B: Anaplastic thyroid cancer (ATC), previously treated BRAF V600E/K/D/R anaplastic thyroid cancer (ATC)Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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)
Time frame
up to 2 years2
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)
Time frame
up to 2 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Memorial Sloan Kettering Cancer Center
Lead sponsor
Verastem, Inc.
Collaborator
Source ClinicalTrials.gov