E-Newsletter - February 2017

Alliance trial takes a closer look at rare Population Subsets

Hürthle Cell Thyroid Cancer - Alliance A091302
Randomized Phase II Study of Sorafenib with or without Everolimus In Patients with Radioactive Iodine Refractory Hürthle Cell Thyroid Cancer

The rate of new thyroid cancers is the fastest growing among all cancers for both men and women with more than 64,000 new cases anticipated this year. About 10-20 percent of thyroid patients develop new tumors in other parts of the body. Surgery, radioactive iodine therapy, and treatment with external beam irradiation are therapeutic options that only relieve symptoms for a subset of patients. Once tumors lose the ability to build up radioactive iodine and are not amenable to loco-regional treatments, therapeutic options are quite limited as traditional chemotherapeutic agents are relatively ineffective. Doxorubicin is the only U.S. Food and Drug Administration approved drug for the treatment of radioactive iodine-refractory thyroid cancer based on limited clinical data generated from the 1980s, and its efficacy is questionable. Treatment options for patients with recurrent and metastatic thyroid cancer not amenable to curative surgery or radioactive iodine are limited; no effective systemic therapy currently exits.

Radioactive iodine is a standard therapy for metastatic Hürthle cell thyroid cancer. If the cancer continues to grow despite this treatment, patients typically receive sorafenib, a drug approved for radioactive iodine-resistant advanced thyroid cancer. In Alliance A091302, Alliance researchers will determine if giving everolimus (an immunosuppressant drug) with sorafenib versus sorafenib alone in treating patients with radioactive iodine-refractory Hürthle cell thyroid cancer will cause more shrinkage of thyroid cancer and prevent it from growing, and whether it could also cause more side effects than sorafenib alone.

Patients will be randomly assigned to one of two groups: sorafenib alone (with the potential to switch to everolimus alone if the cancer continues growing) or sorafenib plus everolimus. Sorafenib works by targeting several proteins involved in cancer growth. Everolimus inhibits a molecule called mTOR, which helps cancer cells grow. Both drugs are taken orally. The study drugs should increase the time it takes the cancer to progress by four and a half months or more compared to the usual approach. About 56 people will participate in this study.

To be eligible for this study (Alliance A091302), patients must meet several criteria, including but not limited to the following:

  • Patients must have Hürthle cell thyroid cancer that cannot be surgically removed or has spread, and continues to grow despite prior treatment with radioactive iodine.

  • At least 90 days must pass between completion of radioactive iodine therapy and entry into the study.

  • For patients who already received chemotherapy, at least four weeks must pass between completion of chemotherapy and study entry.

  • Patients may not have previously received sorafenib or an mTOR inhibitor.

  • Patients must be able to walk and do routine activities for more than half of their normal waking hours.

  • Patients must be age 18 and older.

Refer to the study protocol (Alliance A091302) to learn more about this study, including the trial design, treatment plan and patient eligibility, which can be found on the CTSU menu (ctsu.org) or the Alliance webiste. The Alliance Study Chair is Eric J. Sherman, MD, Memorial Sloan Kettering Cancer Center, e-mail: shermane@mskcc.org. Also see ClinicalTrial.gov Identifier: NCT02143726.

- National Cancer Institute. Surveillance, Epidemiology, and End Results Program. (2015). SEER Stat Fact Sheets: Thyroid Cancer. Retrieved from http://seer.cancer.gov/statfacts/html/thyro.html
- Durante C, Haddy N, Baudin E, et al: Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab 91:2892-9, 2006
- Fagin JA, Tuttle RM, Pfister DG: Harvesting the low-hanging fruit: kinase inhibitors for therapy of advanced medullary and nonmedullary thyroid cancer. J Clin Endocrinol Metab 95:2621-4, 2010
- Pfister DG, Fagin JA: Refractory thyroid cancer: a paradigm shift in treatment is not far off. J Clin Oncol 26:4701-4, 2008


For other articles in this issue of the Alliance E-News newsletter, see below.