Neoplasms

All Conditions

Gland and Hormone Related Diseases

Carcinoma

Thyroid Neoplasms

Thyroid Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive encorafenib PO QD and binimetinib PO BID as in arm I. Patients also receive nivolumab IV over 30 minutes on day 1. Cycles with nivolumab repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Binimetinib

Encorafenib

Matthew Taylor, MD

George Morris, RN

Matthew H. Taylor, MD

Matthew H Taylor

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.

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.

SECONDARY OBJECTIVES:

I. To assess the progression-free survival (PFS) among study participants treated with the combination of encorafenib and binimetinib with or without nivolumab.

II. To assess the overall survival (OS) among study participants treated with the combination of encorafenib and binimetinib with or without nivolumab.

III. To evaluate the duration of response (DOR). IV. To evaluate the safety and tolerability of study participants treated with the combination of encorafenib and binimetinib with or without nivolumab.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive encorafenib orally (PO) once daily (QD) and binimetinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive encorafenib PO QD and binimetinib PO BID as in arm I. Patients also receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles with nivolumab repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Please note: Arm II is closed to accrual. Patients will only be enrolled into Arm I as of March 11th, 2022.

After completion of study treatment patients are followed up at 30 days and then every 6 months for up to 12 months.

Encorafenib and Binimetinib With or Without Nivolumab in Treating Patients With Metastatic Radioiodine Refractory BRAF V600 Mutant Thyroid Cancer

Encorafenib/Binimetinib With or Without Nivolumab for Patients With Metastatic BRAF V600 Mutant Thyroid Cancer

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.

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.

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.

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Encorafenib and Binimetinib With or Without Nivolumab in Treating Patients With Metastatic Radioiodine Refractory BRAF V600 Mutant Thyroid Cancer	NCT04061980	BRAF NP_004324.... BRAF V600E Muta... Metastatic Thyr... Refractory Thyr... Stage IV Differ... Stage IVA Diffe... Stage IVB Diffe...	Binimetinib Encorafenib Nivolumab	18 Years -	Providence Health & Services
Encorafenib and Binimetinib With or Without Nivolumab in Treating Patients With Metastatic Radioiodine Refractory BRAF V600 Mutant Thyroid Cancer	NCT04061980	BRAF NP_004324.... BRAF V600E Muta... Metastatic Thyr... Refractory Thyr... Stage IV Differ... Stage IVA Diffe... Stage IVB Diffe...	Binimetinib Encorafenib Nivolumab	18 Years -	Providence Health & Services

Spots Global Cancer Trial Database for braf np 004324.2:p.v600m