This phase II trial is studying how well tanespimycin works in treating patients with inoperable locoregionally advanced or metastatic thyroid cancer. Drugs used in chemotherapy, such as tanespimycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PRIMARY OBJECTIVES:

I. Determine the 1-year treatment failure rate in patients with inoperable locoregionally advanced or metastatic medullary or differentiated thyroid carcinoma treated with 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) (tanespimycin).

SECONDARY OBJECTIVES:

I. Determine the toxicity of this drug in these patients. Determine the 1-year progression-free rate in patients treated with this drug.

II. Determine the response rate and duration of response in patients treated with this drug.

III. Determine the time to treatment failure and time to subsequent therapy in patients treated with this drug.

IV. Determine the time to disease progression and overall survival of patients treated with this drug.

V. Correlate the incidence rate of RAS, RAF, and RET mutations with clinical outcome in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to type of thyroid carcinoma (medullary vs differentiated).

Patients receive tanespimycin intravenously (IV) over 2-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years from study entry.

Inclusion Criteria:

• Diagnosis of thyroid carcinoma of 1 of the following types:

  • Medullary

  • Differentiated

    • Iodine I 131-resistant disease, defined as failure to incorporate and/or progression of measurable disease after treatment with iodine I 131

• Inoperable locoregionally advanced or metastatic disease

• Measurable disease, defined as ≥ 1 lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan

• No active CNS metastases

• Performance status - ECOG 0-2

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 9.0 g/dL

• Bilirubin ≤ normal

• Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN)

• AST ≤ 1.5 times ULN

• Creatinine ≤ 1.5 times ULN

• QTc < 450 msec for male patients (470 msec for female patients)

• LVEF > 40% by MUGA

• DLCO ≥ 80%

• No cardiac symptoms ≥ grade 2

• No active ischemic heart disease within the past year

• No congenital long QT syndrome

• No left bundle branch block

• No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)

• No myocardial infarction within the past year

• No New York Heart Association class III or IV congestive heart failure

• No poorly controlled angina

• No history of angina (of any sort) within the past 6 months

• No history of uncontrolled dysrhythmias or requiring antiarrhythmic drugs

• No history of cardiac toxicity after treatment with anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)

• No other significant cardiac disease

• No uncontrolled infection

• No history of serious allergic reaction to eggs

• No pulmonary symptoms ≥ grade 2

• No symptomatic pulmonary disease requiring medication including the following:

  • Dyspnea on or off exertion
  • Paroxysmal nocturnal dyspnea
  • Oxygen requirement
  • Significant pulmonary disease (e.g., chronic obstructive/restrictive pulmonary disease)

• No home oxygen need meeting the Medicare criteria

• No history of pulmonary toxicity after treatment with anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinoma

• No active seizure disorder

• More than 4 weeks since prior and no concurrent immunotherapy

• More than 4 weeks since prior biologic therapy

• No concurrent routine or prophylactic colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered

• No other concurrent chemotherapy

• See Disease Characteristics

• More than 4 weeks since prior and no concurrent radiotherapy

• More than 4 weeks since prior radiopharmaceuticals

• No prior radiotherapy to > 25% of bone marrow

• No prior radiotherapy that potentially included the heart in the field (i.e., mantle) or chest

• More than 4 weeks since prior therapeutic surgery for the tumor

• More than 3 months since prior sublingual nitroglycerin

• No other concurrent investigational ancillary therapy

• Concurrent CYP3A4 inhibitors allowed

• No concurrent medications that prolong or may prolong QTc interval