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Name of the Trial

Phase II Study of 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Patients With Inoperable Locoregionally Advanced or Metastatic Medullary or Differentiated Thyroid Carcinoma (MAYO-MC0476). See the protocol summary ³.

Principal Investigators

Dr. Jeffrey Moley, Washington University (St. Louis), and Dr. Robert Smallridge, Mayo Clinic Cancer Center.

Why This Trial Is Important

Most thyroid gland cancers, including follicular and papillary carcinomas, are well differentiated, slow growing, and highly treatable, often by administering radioactive iodine131 both before and after surgery to remove the thyroid. However, some of these differentiated tumors eventually stop taking up iodine, start behaving aggressively, and metastasize. Medullary thyroid cancers (MTC) arise from a different type of thyroid cell and are generally more aggressive. Many patients with MTC will see their cancer return and metastasize after initial treatment.

Surgery is the only curative treatment for most patients with iodine-resistant differentiated thyroid cancer or MTC. Some patients, however, have tumors that cannot be surgically removed (unresectable), and, in other patients, cancer cells have spread to lymph nodes in the neck or to distant sites, such as the lungs, liver, or bones. No effective treatment has been found for these groups of patients, and new treatment options are needed.

In this phase II trial, researchers are studying the effects of treatment with 17-AAG, an antitumor antibiotic drug that targets a protein called heat shock protein 90 (HSP90), in such patients. Many of the proteins implicated in cancer development need HSP90, a member of a class of proteins called molecular chaperones, to help them achieve their correct functional shape and cellular location. Cancer cells often contain higher levels of HSP90 than normal cells, helping them to grow uncontrollably. In laboratory experiments with MTC, papillary and follicular thyroid carcinomas, and other cancer types, 17-AAG has proven effective in inhibiting cancer cell growth by interfering with the chaperone function of HSP90, which leads, in turn, to the degradation of cellular proteins that promote uncontrolled growth.

"While most thyroid cancers are very slow-growing and survival rates can be good at 15 years or longer, this trial is for that subset of patients with aggressively metastatic disease," said Dr. Moley. "These patients face a difficult challenge, and there haven't been many trials mounted to address their plight."

For More Information

See the lists of entry criteria and trial contact information ³ or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The call is toll free and confidential.

Glossary Terms

A substance being studied in the treatment of cancer. It is made from an antibiotic called geldanamycin. 17-AAG helps cause the breakdown of certain proteins in the cell, and may kill cancer cells. It is a type of antineoplastic antibiotic and a type of HSP90 inhibitor. Also called 17-N-allylamino-17-demethoxygeldanamycin and tanespimycin.

In cancer, refers to how mature (developed) the cancer cells are in a tumor. Differentiated tumor cells resemble normal cells and tend to grow and spread at a slower rate than undifferentiated or poorly differentiated tumor cells, which lack the structure and function of normal cells and grow uncontrollably.

Cancer that forms in follicular cells in the thyroid. It grows slowly and is highly treatable.

One of a group of proteins that help protect cells from stresses such as heat, cold, and low amounts of oxygen or glucose (sugar). Heat-shock proteins help other proteins function in normal cells and may be present at high levels in cancer cells. Blocking the activity of a heat-shock protein called HSP90 is being studied in the treatment of cancer. Other heat-shock proteins including HSP70 and gp96 are being studied in vaccines to treat cancer. Also called HSP and stress protein.

Cancer that develops in C cells of the thyroid. The C cells make a hormone (calcitonin) that helps maintain a healthy level of calcium in the blood.

Cancer that forms in follicular cells in the thyroid and grows in small finger-like shapes. It grows slowly, is more common in women than in men, and often occurs before age 45. It is the most common type of thyroid cancer.

A radioactive form of iodine, often used for imaging tests or to treat an overactive thyroid, thyroid cancer, and certain other cancers. For imaging tests, the patient takes a small dose of radioactive iodine that collects in thyroid cells and certain kinds of tumors and can be detected by a scanner. To treat thyroid cancer, the patient takes a large dose of radioactive iodine, which kills thyroid cells. Radioactive iodine is also used in internal radiation therapy for prostate cancer, intraocular (eye) melanoma, and carcinoid tumors. Radioactive iodine is given by mouth as a liquid or in capsules, by infusion, or sealed in seeds, which are placed in or near the tumor to kill cancer cells.