E-Newsletter - Summer 2017

Advanced Anaplastic Thyroid Cancer - Alliance A091305
Phase 2 Study of Efatutazone, An Oral PPAR Agonist, in Combination with Paclitaxel in Patients with Advanced Anaplastic Thyroid Cancer


While thyroid cancer is the most common endocrine malignancy, anaplastic thyroid cancer (ATC) is extremely rare. This year, the anticipated incidence rate for thyroid cancer in the United States is more than 64,000 newly diagnosed cases, of which ATC comprises less than two percent. ATC is an undifferentiated, highly aggressive tumor with a median survival of five months from diagnosis and a one-year survival of no more than 20 percent. Patients with ATC die from distant metastases or loco-regional disease that obliterates the airway. Median age at diagnosis ranges between 63 and 74 years. ATC affects women more frequently than men. Symptoms at diagnosis include hoarseness (due to invasion of the trachea, larynx, or recurrent laryngeal nerve), dysphagia (due to invasion of the esophagus) and dyspnea. A diagnosis of ATC frequently follows a prior or concurrent diagnosis of well‑differentiated thyroid cancer or benign nodular thyroid disease, and synchronous pulmonary metastases may be present in up to 50 percent of patients. If detected early, extensive surgery offers the best chance of cure. Combination chemotherapy and hyper-fractionated radiotherapy are used with limited success, but several clinical studies using taxanes have shown benefit. More effective targeted therapies based on a better understanding of the molecular and signaling pathways that are disrupted in ATC are needed.

In Alliance A091305, Alliance researchers will determine how well inolitazone dihydrochloride (efatutazone dihydrochloride) and paclitaxel work in treating patients with anaplastic thyroid cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Drugs used in chemotherapy, such as efatutazone dihydrochloride and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells by stopping them from dividing or by stopping them from spreading. It is not yet known whether efatutazone in combination with paclitaxel is more effective than paclitaxel alone in treating patients with advanced anaplastic thyroid cancer.

This is a phase II study for patients with advanced anaplastic thyroid cancer. Patients will be treated with efatutazone in combination with paclitaxel. Treatment will consist of continuous cycles administered every 21 days. Treatment will continue until disease progression, unacceptable adverse events, or a minimum of two cycles beyond a complete response.

To be eligible for this study (Alliance A091305), patients must meet several criteria, including but not limited to the following:

  • Patients must have histologically or cytologically diagnosed advanced anaplastic thyroid cancer; patients must have measurable disease.
  • Patients must have either metastatic (stage IVC) or locally advanced unresectable disease (stage IVB).
  • Patients should have resolution of any toxic effects of prior therapy (except alopecia) to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, grade 1.
  • There is no limit to the number of prior lines of treatment a patient has received.
  • No treatment with chemotherapy, radiation therapy, immunotherapy, biological therapy, hormonal therapy, or other thiazolidinediones less than or equal to 21 days before study registration.
  • No prior taxane therapy less than or equal to six months, except as a radiosensitizer.

To learn more about this study, refer to the study protocol (Alliance A091305), which can be found on the CTSU menu (ctsu.org) and includes complete information on the trial design, treatment plan and patient eligibility. The Alliance Study Chair is Robert C. Smallridge, MD, Mayo Clinical Cancer Center, e-mail: smallridge.robert@mayo.edu. Also see ClinicalTrial.gov Identifier: NCT02152137.

* PPAR is an acronym for peroxisome proliferator-activated receptor, which are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. They play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms.


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