Phase II Trial Evaluating Gleevec (Imatinib Mesylate Formerly Known as STI571) in Patients With Anaplastic Thyroid Cancer
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
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
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.
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
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall response (complete and partial response) rates at the first response assessment (i.e. 8 weeks following the start of Gleevec), following best local control with surgery or radiation/chemoradiation
Francis P Worden, MD
University of Michigan Cancer Center
United States: Institutional Review Board
|University of Michigan Cancer Center||Ann Arbor, Michigan 48109|