Trial Evaluating Gleevec in Patients With Anaplastic Thyroid Carcinoma

Thyroid Cancer Clinical Trial

Official title: Phase II Trial Evaluating Gleevec (Imatinib Mesylate Formerly Known as STI571) in Patients With Anaplastic Thyroid Cancer

Status Terminated

Clinical Trial Summary

Anaplastic thyroid cancers are rare, aggressive tumors. Standard treatment options include surgery and chemoradiation. Few treatment options are available once metastases develop. Recent data suggest that Imatinib (Gleevec) may be advantageous in this patient population. Patients who have been treated for anaplastic thyroid cancer with chemoradiation or surgery who develop recurrent or metastatic disease outside of the field of radiation are eligible. Patients will be treated with Imatinib 400 mg two times a day for eight weeks, followed by radiologic assessment. Patients will be treated until disease progression or a complete response is obtained.

Clinical Trial Description

Anaplastic thyroid carcinomas (ATC) are high grade neoplasms, which account for approximately 2% to 5% of primary malignant thyroid tumors but more than 50% of thyroid cancer deaths. Because therapies for anaplastic thyroid carcinoma are very limited with even early stage disease, new approaches for treating this devastating cancer are needed. Recently, imatinib mesylate (Gleevec®), formerly known as STI571, has been approved for the treatment of chronic myelogenous leukemia and for treatment of gastrointestinal stromal tumors, expressing the c-Kit tyrosine kinase. Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor, c-Kit, and inhibits PDGF- and SCF-mediated cellular events. Recent data suggest that many if not most, anaplastic thyroid cancers express PDGF receptors, and that these receptors are functional. Additional preclinical work from Japan demonstrates that c-Abl is overexpressed in p53 mutated/deficient anaplastic thyroid carcinoma cell lines and that select inhibition of c-Abl activity by STI571 has a dramatic cytostatic effect in these cells.

Additional data suggest that many, if not most, anaplastic thyroid cancers express PDGF receptors, and that these receptors are functional. Since activation of PDGF receptors is associated with the growth of other tumors and c-Abl is overexpressed in p53-mutated anaplastic thyroid carcinoma cell lines, it seems appropriate to test Gleevec as a therapy for patients with anaplastic thyroid cancer. The specific hypothesis to be tested is that anaplastic thyroid cancers that overexpress PDGF receptors or Abl will respond to Gleevec therapy. The lack of any accepted efficacious therapies for anaplastic thyroid cancer, the poor prognosis of this cancer, and the relatively low toxicity of Gleevec justify this proposed trial.

Patients with anaplastic thyroid carcinoma who are status post best local control with surgery/chemoradiation, who have measurable disease outside their previous field of radiation, are eligible.

The Primary Objective of this study is:

1. To determine the overall response (complete and partial response) rates of patients with anaplastic thyroid cancer treated with Gleevec at the first response assessment (i.e. 8 weeks following the start of Gleevec), following best local control with surgery or radiation/chemoradiation.

The Secondary Objectives include:

1. To measure the grade III/IV toxicities experienced by patients with anaplastic thyroid cancer who are treated with Gleevec.

2. To determine the time to obtain complete or partial responses in patients with anaplastic thyroid cancer treated with Gleevec, following best local control with surgery or radiation/chemoradiation.

Treatment Plan:

Patients will be treated with Imatinib (Gleevec) 400 mg two times a day for eight weeks after which radiologic imaging will be obtained to assess response. Patients who attained a complete response will be treated with four additional weeks of Imatinib. Patients who attain a partial response or stable disease will be treated until a complete response is attained, or until disease progression. All patients with progression of disease will be taken off the study. Patients continuing on the study, will undergo radiologic imaging every eight weeks following their initial response assessment. All patients will be followed until death. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

• NCT number: NCT00115739
• Study type: Interventional
• Source: University of Michigan Cancer Center
• Status: Terminated
• Phase: Phase 2
• Start date: February 2004
• Completion date: August 2010