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


Phase 2
18 Years
N/A
Not Enrolling
Both
Thyroid Cancer

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Trial Information

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 (GleevecĀ®), 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.


Inclusion Criteria:



- Patients with histologically confirmed anaplastic thyroid carcinoma, who have
measurable disease.

- Patients with brain metastases are eligible if they have been stable for at least six
weeks post-radiation therapy.

- Age 18 years, male or female.

- Karnofsky performance status (KPS) of > 70%.

- Life expectancy of at least 12 weeks.

- Hematologic: ANC 1,500 mm3, hemoglobin 8.0 g/dl, platelets 100,000/mm3

- Normal serum calcium level within normal limits for the institution documented within
14 days prior to registration.

- All patients (including those with liver metastases) must have adequate hepatic
function as defined by a serum bilirubin 1.5 x the institutional upper limit of
normal (ULN), and ALT and AST <2.5 x ULN, obtained within 14 days prior to
registration.

- Patients must have a serum creatinine less than 1.5 x the institutional upper limits
of normal (adjusted for age) within 14 days of registration.

- Women of childbearing potential must have a negative pregnancy test at baseline,
prior to receiving any study drug. (Pregnant or lactating patients are excluded.)

- Patients of reproductive potential must practice effective contraception while on
study and for at least six months after receiving the last dose of study drug.

- All patients must sign an informed consent prior to enrollment.

- No prior history of non-thyroid malignancy, except adequately treated skin cancer or
in situ cervical carcinoma or any other cancer in complete remission for at least two
years.

- Prior chemotherapy, chemoradiation, radiation therapy, or surgery must have been
completed at least 28 days prior to registration, and all toxicities must have
resolved. Patients who have been treated with nitrosourea or mitomycin C must be off
of these drugs for at least 6 weeks prior to registration.

- Patients must be able to take oral medications.

Exclusion Criteria:

- Anaplastic thyroid cancer that does not overexpress PDGF receptors or c-Abl by
immunohistochemistry

- Any medical or psychiatric illness which, in the opinion of the principal
investigator, would compromise the patient's ability to tolerate this treatment
regimen.

- No concurrent radiotherapy (to the primary tumor) or chemotherapy may be given to the
patient during the administration of the study drug.

- Pregnant or lactating women, women of childbearing potential with either a positive
pregnancy test (PPT) at baseline, or sexually active females not using reliable
contraceptive methods while on study and for at least six months after chemotherapy.
(Postmenopausal women must have been amenorrheic for least 12 months to be considered
of non-childbearing potential).

- Sexually active males not using reliable contraceptive methods while on the study and
for at least six months after chemotherapy.

- Patients with malabsorption syndromes will be excluded.

- Serious concurrent infections.

- Patients who have had previous organ allografts will be excluded.

- Prisoners.

- Patients with chronic liver disease (i.e chronic active hepatitis and cirrhosis).

- Patients with a known diagnosis of human immunodeficiency virus (HIV) infection.

- Patients who have had major surgery within 2 weeks of study entry.

- Patients with grade III/IV cardiac problems as defined by the New York Heart
Association Criteria (i.e. congestive heart failure, myocardial infarction within 6
months of study entry).

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

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

Outcome Time Frame:

12 months

Safety Issue:

No

Principal Investigator

Francis P Worden, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Michigan Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

UMCC 2003-044

NCT ID:

NCT00115739

Start Date:

February 2004

Completion Date:

August 2010

Related Keywords:

  • Thyroid Cancer
  • Anaplastic Thyroid Cancer
  • Thyroid Neoplasms
  • Thyroid Diseases

Name

Location

University of Michigan Cancer CenterAnn Arbor, Michigan  48109