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This study assesses efficacy of treatment with XL092 (Zanzalintinib) in radioactive iodine refractory Differentiated Thyroid Cancer patients by evaluating the proportion of patients alive and without progression at 12 months, by evaluating Progression Free Survival, evaluating the overall survival time, safety and tolerability of the study drug and characterize the quality of life. Along with that the study would assess immune cell landscape before and after the treatment, and study genomic changes before and after treatment.

The duration for this study will last for approximately 26 months or until the time of progression of cancer. The participant will be asked to start the treatment within 14 days of screening. XL092 (study drug) is an oral agent and will be provided as tablets at 100mg dose to be taken by mouth once a day.

Each treatment cycle is 21 days (every three weeks). Participants will be followed from the end of study treatment either at a routine clinic visit or by phone call every 3 months for 12 months to document survival, patient health status and disease progression.

The purpose of this study is to understand the treatment journey for many patients with advanced head and neck squamous cell carcinoma (HNSCC) including looking at changes in genes and proteins associated with their cancer throughout the course of treatment. Part of this research may identify genetic changes in their tumor that are different from their normal genes.

Note: This is only a partial description of the study. Please contact the Robert H. Lurie Comprehensive Cancer Center of Northwestern University if you are interested in the 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.

Note: This is only a partial description of the study. Please contact the Robert H. Lurie Comprehensive Cancer Center of Northwestern University if you are interested in the trial.