This phase II trial studies how well encorafenib and binimetinib given with or without nivolumab works in treating patients with BRAF V600 mutation positive thyroid cancer that has spread to other places in the body (metastatic) and does not respond to radioiodine treatment (refractory). Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The trial aims to find out if the combination of encorafenib and binimetinib, with and without study nivolumab, is a safe and effective way to treat metastatic radioiodine refractory thyroid cancer.
Description: ORR is defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria. ORR at 6 months will be assessed using the efficacy evaluable analysis set. A point and 90% exact binomial confidence interval will be provided for each arm.Measure: Overall response rate (ORR) Time: From the start of randomization up to 6 months from first dose of study drugs
Description: The Kaplan-Meier method will be used to estimate PFS and the summary statistics (e.g., 12-month survival, median survival, 95% confidence intervals) will be provided for each arm.Measure: Progression free survival (PFS) Time: From date of randomization until either tumor progression (per RECIST v1.1) or death, assessed for up to 12 months
Description: The Kaplan-Meier method will be used to estimate OS and the summary statistics (e.g., 12-month survival, median survival, 95% confidence intervals) will be provided for each arm.Measure: Overall survival Time: From date of randomization until the date of death from any cause, assessed for up to 1 year
Description: The Kaplan-Meier method will be used to estimate DOR, and the summary statistics (e.g., 12-month survival, median survival, 95% confidence intervals) will be provided for each arm. DOR will be estimated only among responders (i.e. participants achieving at least once CR or PR). Data visualization tools such as waterfall plots (% change in tumor size) or swimmer plot (DOR) will be used to display the data.Measure: Duration of response (DOR) Time: From date of first documented CR or PR up to first documented progression or death due to any cause, assessed for up to 1 year
Description: Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Using the safety evaluable analysis set, the incidence of having grade >= 3 adverse events will be determined for study participants that received at least one dose of their assigned treatment. The point estimate and 95% confidence interval will be reported for each arm.Measure: Incidence of grade >= 3 toxicities Time: From the first dose of assigned study intervention until 90 days from the last dose of assigned study intervention
There is one SNP
ability to understand the patient information, give informed consent, comply with the study protocol or complete the study BRAF NP_004324.2:p.V600M BRAF V600E Mutation Present Metastatic Thyroid Gland Carcinoma Refractory Thyroid Gland Carcinoma Stage IV Differentiated Thyroid Gland Carcinoma AJCC v8 Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v8 Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v8 Carcinoma Thyroid Neoplasms Thyroid Diseases PRIMARY OBJECTIVES: I. To assess the overall rate of response among study participants treated with the combination of encorafenib and binimetinib, with or without nivolumab. --- V600E ---