Arsenic Trioxide in Treating Men With Germ Cell Cancer

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.

Eligibility Criteria:
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