About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patient must be ≥ 18 years of age
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Papillary thyroid carcinoma including histological variants of papillary thyroid carcinoma (PTC) such as follicular variant, tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin-like, trabecular, tumor with nodular fasciitis-like stroma, Hürthle cell variant of papillary carcinoma, poorly differentiated.
Follicular thyroid carcinoma including histological variants of follicular thyroid carcinoma (FTC) such as Hürthle cell, clear cell, insular, and poorly differentiated
Disqualifiers
None
Trial design
Parallel
Treatments tested in this trial
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Cabozantinib
DrugGiven PO
Computed Tomography
Procedure/SurgeryUndergo CT scan
Dabrafenib
DrugGiven PO
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Questionnaire Administration
Other interventionAncillary study
Trametinib
DrugGiven PO
Treatment groups
Trial outcomes
Primary outcomes
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.
Secondary outcomes
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.
Overall survival
Median and 95% CI will be estimated in each arm using the Kaplan-Meier method.
Duration of response
Median and 95% CI will be estimated in each arm using the Kaplan-Meier method.
PFS2
Median and 95% CI will be estimated in each arm using the Kaplan-Meier method.
Other outcomes
Patient tolerability
Will assess patients tolerability of treatment using the Functional Assessment of Cancer Therapy-General (FACT G)7 and general quality of life using the FACT-GP.
Treatment effect
The corresponding 95% CIs will be provided.
Treatment effect by sex
The corresponding 95% CIs will be provided.
Treatment effect by race
The corresponding 95% CIs will be provided.
Sponsors and contacts
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