Arsenic Trioxide in Treating Men With Germ Cell Cancer

Phase II Study Of Arsenic Trioxide In Patients With Refractory Germ Cell Malignancies

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of arsenic trioxide in treating men who have germ cell cancer that has not responded to previous treatment.

OBJECTIVES:

• Determine the response rate (confirmed complete and partial responses) in men with refractory testicular or extragonadal germ cell malignancies treated with arsenic trioxide.
• Determine the overall and progression-free survival of patients treated with this drug.
• Determine the qualitative and quantitative toxic effects of this drug in these patients.
• Assess the biomarker response rate in patients with elevated biomarkers treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive arsenic trioxide IV over 1-2 hours on days 1-5. Courses repeat every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity. Patients who achieve a confirmed complete or partial response receive up to 3 additional courses past response.

Patients are followed every 2 months for 3 years or until disease progression.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 10-40 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed testicular or extragonadal germ cell cancer

• Refractory disease, defined by at least 1 of the following criteria:

  • Disease progression during or within 4 weeks of cisplatin-containing regimen

    • Progression is defined as the appearance of new or progression of known locally advanced or metastatic disease or a rise in tumor markers (beta-human chorionic gonadotropin (beta-HCG) or alpha fetoprotein (AFP)) by at least 50% relative to the nadir
    • When the only evidence of germ cell progression or recurrence before study entry is the appearance of a new lesion in the absence of tumor marker elevation, a biopsy is required to confirm the diagnosis

  • Disease recurrence after at least 2 chemotherapy regimens, one of which includes high-dose therapy (chemotherapy with stem cell support)

  • Disease recurrence after at least 2 chemotherapy regimens and not eligible for high-dose therapy

• At least 1 of the following:

  • Unidimensionally measurable disease

    • Soft tissue, irradiated within the past 2 months, is not considered measurable

  • Elevated beta-HCG (more than 20 mIU/mL)

  • AFP greater than 2 times upper limit of normal

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Sex:

• Male

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• WBC at least 3,000/mm^3

Hepatic:

• Bilirubin less than 2.5 times upper limit of normal (ULN)
• SGOT less than 5 times ULN
• Alkaline phosphatase less than 5 times ULN

Renal:

• Creatinine no greater than 2.5 times ULN OR
• Creatinine clearance at least 40 mL/min
• Potassium normal
• Magnesium normal
• No renal dialysis

Cardiovascular:

• No prior torsades de pointes-type ventricular arrhythmia
• No prolonged QT interval (greater than 450 msec) on ECG in presence of normal potassium and magnesium

Other:

• Fertile patients must use effective contraception
• No active serious infection not controlled by antibiotics
• No known hypersensitivity to arsenic
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II disease in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics
• More than 28 days since prior cytotoxic agents

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 28 days since prior radiotherapy and recovered

Surgery:

• Not specified

Other:

• More than 28 days since prior experimental agents
• No concurrent or planned drugs known to prolong the QT interval