A Phase II Study of Trametinib to Enhance Radioactive Iodine (RAI) Uptake in Patients with RAI-Resistant Recurrent or Metastatic Thyroid Cancer

Full Title

A Phase 2 Study of Trametinib in Combination with Radioiodine (RAI) for RAS Mutant or RAS/RAF Wild-Type, RAI-Refractory Recurrent and/or Metastatic Thyroid Cancers (NCI #9446)

Purpose

Radioactive iodine (RAI) is the standard treatment for thyroid cancer. But in some patients, the thyroid cancer does not absorb enough RAI to shrink. Doctors are therefore seeking better therapies for such RAI-resistant thyroid cancer.

The activation of two proteins called MEK1 and MEK 2 (MEK1/2) is one reason that thyroid cancer may not absorb enough RAI. MEK1/2 can be activated by mutations in the BRAF or Ras genes, and also in tumors that do not contain these mutations. One small clinical study showed that a drug that blocks MEK1/2 activity increased RAI absorption in thyroid cancers with Ras mutations as well as those without any Ras or BRAF mutations.

Trametinib is a drug approved for treating metastatic melanoma which works by blocking MEK1/2 activity. In this study, researchers want to see if giving trametinib in patients with RAI-resistant recurrent or metastatic thyroid cancers — either cancers with a Ras mutation or without any BRAF or Ras mutations — can increase the absorption of RAI. They will use a form of RAI called iodine-124 to monitor changes in iodine uptake that occur with drug treatment.

If trametinib enhances the uptake of iodine-124, doctors will recommend treatment with trametinib plus iodine-131 — the type of RAI typically used to treat thyroid cancer. Patients whose RAI uptake is not enhanced by trametinib may be able to continue taking trametinib alone. Trametinib is taken orally (by mouth).

Eligibility

To be eligible for this study, patients must meet several criteria, including but not limited to the following:

  • Patients must have RAI-resistant recurrent or metastatic thyroid cancer that either contains mutated Ras or no mutations in BRAF or Ras.
  • At least 6 months must pass between completion of prior RAI therapy and entry into the study. At least 4 weeks must pass since any prior radiation therapy, chemotherapy, or targeted therapy.
  • Patients must be able to walk and do routine activities for more than half of their normal waking hours.
  • This study is for patients age 18 and older.

For more information about this study and to inquire about eligibility, please contact Dr. Alan L. Ho at 646-888-4235.

Protocol

13-157

Phase

II

Investigator

Diseases

Locations