Sunitinib in Treating Patients With Metastatic Germ Cell Tumors That Have Relapsed or Not Responded to Treatment

OBJECTIVES:

Primary

• Determine the efficacy of sunitinib malate in patients with refractory or relapsed metastatic germ cell tumors.

Secondary

• Determine the safety of this drug in these patients.
• Determine the time to tumor response and duration of tumor response in patients treated with this drug.

OUTLINE: This is a open-label study.

Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed at 28 days and then periodically thereafter.

DISEASE CHARACTERISTICS:

• Histologically confirmed seminoma or nonseminoma germ cell tumors (GCT)

• Refractory or relapsed disease
• Metastatic disease
• Progressive disease after prior cisplatin-based chemotherapy AND meets 1 of the following criteria for salvage therapy:

• Not a candidate for potentially curative therapy
• Received prior high-dose chemotherapy regimens
• Declines potentially curative therapy (mediastinal GCT or primary refractory GCT)
• Measurable disease*, defined as 1 of the following:

• At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• Elevation of alpha-fetoprotein > 15 ng/mL and/or elevation of human chorionic gonadotropin > 2.2 mIU/L
• NOTE: *Patients with radiographically measurable disease only must have ≥ 1 site that has not undergone prior irradiation

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9.0 g/dL
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• AST and ALT ≤ 2.5 times ULN (unless elevated liver function abnormalities due to underlying malignancy)
• LVEF ≥ 50% by MUGA
• No grade 3 hemorrhage within the past 4 weeks
• None of the following within the past 6 months:

• Myocardial infarction
• Severe or unstable angina
• Coronary or peripheral artery bypass graft
• Symptomatic congestive heart failure
• Cerebrovascular accident or transient ischemic attack
• Pulmonary embolism
• No prolonged QTc interval (i.e., QTc > 450 msec for males and > 470 msec for females)
• No ongoing cardiac dysrhythmias ≥ grade 2
• No uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal therapy
• No active infection
• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study compliance, according to the study investigator
• Not pregnant or nursing

• Negative sonogram required to exclude pregnancy
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior sunitinib malate
• More than 4 weeks since prior major surgery and recovered
• More than 4 weeks since prior radiotherapy and recovered
• Concurrent palliative radiotherapy to metastatic lesion(s) allowed provided ≥ 1 measurable lesion has not been irradiated
• No concurrent therapeutic doses of warfarin

• Low-dose oral warfarin (up to 2 mg daily) for prophylaxis and treatment or heparin products at prophylactic or treatment doses allowed
• No other concurrent investigational or approved anticancer therapies, including chemotherapy, biologic response modifiers, hormone therapy, or immunologic-based treatment

• Concurrent participation in supportive care or nontreatment trials (e.g., quality-of-life or laboratory analyses) allowed