Bortezomib in Treating Patients With Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well bortezomib works in treating patients with metastatic thyroid cancer that did not respond to radioactive iodine therapy.

OBJECTIVES:

Primary

• Determine the efficacy of bortezomib, in terms of tumor response rate, in patients with metastatic papillary or follicular thyroid cancer unresponsive to prior radioiodine therapy.

Secondary

• Determine the clinical activity of this drug, in terms of progression-free survival, in patients treated with this drug.

OUTLINE: This is an open-label, multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed differentiated thyroid cancer

  • Papillary or follicular type, including, but not limited to, any of the following variants:

    • Hurthle cell (oxyphilic)
    • Insular
    • Columnar cell
    • Tall cell
  • Metastatic disease

• Measurable disease

  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
  • No prior radiotherapy to the only measurable lesion

• Unresponsive to prior radioiodine therapy

  • No radioiodine uptake in the measured metastatic tumor by radioiodine scan* NOTE: *Must have had ≥ 1 radioiodine scan since the last radioiodine treatment
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal
• Bilirubin normal

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy
• No more than 2 prior chemotherapy regimens

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

• At least 6 months since prior external beam radiotherapy for locoregional disease in the thyroid bed or to the cervical or upper mediastinal lymph nodes

  • Dose ≤ 6,000 cGy
• At least 6 months since prior radioiodine therapy
• No prior external radiotherapy to the measured tumor

Surgery

• Prior thyroidectomy allowed

Other

• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapy