Study of Targeted Therapy vs. Chemotherapy in Patients With Thyroid Cancer
NCT Number: NCT06475989
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Refractory Differentiated Thyroid Gland Carcinoma
Interventions: PROCEDURE: Biospecimen Collection|DRUG: Cabozantinib|PROCEDURE: Computed Tomography|DRUG: Dabrafenib|PROCEDURE: Magnetic Resonance Imaging|OTHER: Questionnaire Administration|DRUG: Trametinib
Sponsor: ECOG-ACRIN Cancer Research Group
Collaborators: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 264
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-13
Completion Date: 2030-09-30

Summary:
This phase III trial compares the effect of cabozantinib versus combination dabrafenib and trametinib for the treatment of patients with differentiated thyroid cancer that does not respond to treatment (refractory) and which expresses a BRAF V600E mutation. Cabozantinib is in a class of medications called receptor tyrosine kinase inhibitors. It binds to and blocks the action of several enzymes which are often over-expressed in a variety of tumor cell types. This may help stop or slow the growth of tumor cells and blood vessels the tumor needs to survive. Dabrafenib is an enzyme inhibitor that binds to and inhibits the activity of a protein called B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. Trametinib is also an enzyme inhibitor. It binds to and inhibits the activity of proteins called MEK 1 and 2, which play a key role in activating pathways that regulate cell growth. This may inhibit the growth of tumor cells mediated by these pathways. The usual approach for patients with thyroid cancer is targeted therapy with dabrafenib and trametinib. This trial may help researchers decide which treatment option (cabozantinib alone or dabrafenib in combination with trametinib) is safer and/or more effective in treating patients with refractory BRAF V600E-mutated differentiated thyroid cancer.

Primary Outcome Measures: Progression free survival (PFS), PFS will be compared between the two groups using a stratified log-rank test with one-sided type I error of 0.05. Median PFS and 95% confidence interval (CI) for each treatment arm will be estimated using the Kaplan-Meier method. The stratified hazard ratio and 95% CI will be estimated using a Cox proportional hazard model with treatment group as the independent variable., From randomization to radiographic progression of disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause, up to 5 years
Secondary Outcome Measures: Objective response, Will be assessed based on international criteria proposed by the RECIST 1.1 guideline. Response (complete and partial responses) rate will be estimated. Will be compared using the Fisher's exact test., Up to 5 years|Overall survival, Median and 95% CI will be estimated in each arm using the Kaplan-Meier method., From randomization to death from any cause, up to 5 years|Duration of response, Median and 95% CI will be estimated in each arm using the Kaplan-Meier method., From confirmed response (complete response or partial response) to progression among patients who achieve a response, up to 5 years|PFS2 - the time from randomization to progression on subsequent therapy or death from any cause (whichever occurs first), Median and 95% CI will be estimated in each arm using the Kaplan-Meier method. PFS2 will be measured for every patient. For patients who receive a next line of therapy, PFS2 will be measured from the time of randomization to radiographic progression on the next line of therapy after the protocol-assigned therapy, or death from any cause, whichever occurs first. If patients are alive and have not had progression on the next of line therapy, they will be censored at the last assessment on the next line of therapy, and PFS2 will be measured from the time of randomization to the last assessment. For patients who do not receive the next line of therapy, PFS2 will be measured from the time of randomization to last assessed on the protocol-assigned therapy and will be censored unless death occurs, in which case death will count as an event., From randomization to progression on subsequent therapy or death from any cause, up to 5 years|Incidence of adverse events, Using the National Cancer Institute's Common Terminology Criteria for Adverse Events. Response rate and grade 3 or higher toxicity rates will be compared using the Fisher's exact test between the two arms., at 2 weeks, 4 weeks, 8 weeks, 16 weeks, and then every 12 weeks after the 16-week confirmatory scan
Other Outcome Measures: Patient tolerability, Will assess patients tolerability of treatment using the Functional Assessment of Cancer Therapy-General (FACT G)7., At baseline, 4, 8, 16, and 28 weeks