A Phase II Trial of 17-Allylaminogeldanamycin (17AAG) in Advanced Medullary and Differentiated Thyroid Carcinoma

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