RATIONALE: Drugs used in chemotherapy, such as 3-AP, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of 3-AP in treating patients who have locally recurrent or metastatic renal cell (kidney) carcinoma (cancer).

Condition	Treatment or Intervention	Phase
recurrent renal cell cancer stage III renal cell cancer Stage IV Renal Cell Cancer	Drug: 3-AP  Procedure: chemotherapy	Phase II

OBJECTIVES: Primary

• Determine the efficacy of 3-AP (Triapine®), in terms of objective response rate, in patients with previously untreated locally recurrent or metastatic renal cell carcinoma.

Secondary

• Determine the adverse events and tolerability of this drug in these patients.
• Determine the time to disease progression and overall survival of patients treated with this drug.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive 3-AP (Triapine®) IV over 2 hours on days 1-4 and 15-18. Treatment repeats every 28 days for up to 6 courses (for stable patients) in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) receive 1 additional course after documentation of CR. Patients who achieve a partial response (PR) receive 2 additional courses after documentation of stable PR.

Patients are followed every 4 weeks until relapse and then every 3 months for up to 2 years.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed renal cell carcinoma
• Locally recurrent OR metastatic disease
• Incurable by standard therapy
• Clinically and/or radiologically measurable disease
• At least 1 unidimensionally measurable lesion* at least 20 mm by x-ray, physical exam, or non-spiral CT scan OR at least 10 mm by spiral CT scan
• If the sole site of measurable disease is in a previously irradiated field, there must be documented disease progression at that site NOTE: *Bone lesions are not considered measurable disease
• No documented brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No glucose-6-phosphate dehydrogenase (G6PD) deficiency* NOTE: *Screening for G6PD deficiency is required for patients of African, Asian, or Mediterranean descent

Hepatic

• Bilirubin normal
• AST or ALT no greater than 2.5 times upper limit of normal (ULN)

Renal

• Creatinine no greater than 1.5 times ULN
• Creatinine clearance at least 50 mL/min

Cardiovascular

• No myocardial infarction within the past 6 months
• No symptomatic congestive heart failure
• No unstable angina
• No active cardiomyopathy
• No cardiac arrhythmia
• No uncontrolled hypertension

Pulmonary

• No pulmonary disease requiring oxygen

Immunologic

• HIV negative
• No known hypersensitivity to compounds of similar chemical or biological composition to 3-AP (Triapine®)
• No active uncontrolled or serious infection
• No immunodeficiency

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other prior malignancy except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumor with no evidence of disease for at least 5 years
• No history of significant neurologic or psychiatric disorder (e.g., uncontrolled psychotic disorders) that would preclude giving informed consent or complying with study requirements
• No active peptic ulcer disease
• No other serious illness or medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 3 months since prior interferon for advanced or recurrent disease
• No other prior immunotherapy for advanced or recurrent disease
• No prior gene therapy

Chemotherapy

• No prior systemic chemotherapy for advanced or recurrent disease

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy (except low-dose nonmyelosuppressive radiotherapy) and recovered

Surgery

• At least 2 weeks since prior major surgery

Other

• No prior investigational anticancer agents
• No other concurrent anticancer agents or therapy
• No other concurrent investigational therapy
• No concurrent anticoagulants
• Concurrent nontherapeutic warfarin or heparin allowed

Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
Canada, British Columbia
      British Columbia Cancer Agency, Vancouver,  British Columbia,  V5Z 4E6,  Canada
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada
Canada, Ontario
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Margaret and Charles Juravinski Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Toronto General Hospital, Toronto,  Ontario,  M5G 2C4,  Canada
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada
Canada, Quebec
      Centre Hospitalier de l'Universite de Montreal, Montreal,  Quebec,  H2L-4M1,  Canada

Study chairs or principal investigators

Jennifer Knox, MD,  Study Chair,  Toronto General Hospital   

Study ID Numbers:  CDR0000347409; CAN-NCIC-IND161; NCI-NCIC-161
Record last reviewed:  November 2004
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075660
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-16