UCN-01 in Treating Patients With Advanced or Metastatic Kidney Cancer

A Phase 2 Study Of UCN-01 In Advanced Renal Cell Carcinoma

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 UCN-01 in treating patients who have unresectable stage III or stage IV kidney cancer.

OBJECTIVES:

• Determine the efficacy of UCN-01, in terms of time to objective progression, in patients with stage IV or unresectable stage III renal cell carcinoma.
• Determine the objective response rate in patients treated with this drug.

OUTLINE: Patients receive UCN-01 IV over 3 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 21-61 patients will be accrued for this study within 15 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed stage IV or unresectable stage III renal cell carcinoma

  • Metastatic disease must be amenable to biopsy or appropriate for nephrectomy before study therapy

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

• No known prior or concurrent CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy:

• More than 3 months

Hematopoietic:

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

Hepatic:

• Bilirubin normal
• AST/ALT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No history of clinically significant coronary artery disease
• No symptomatic cardiac dysfunction
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Pulmonary:

• No symptomatic pulmonary dysfunction

Other:

• No prior allergic reactions to compounds of similar chemical or biological composition to UCN-01
• No other uncontrolled concurrent illness
• No active or ongoing infection
• No known immune deficiency
• No psychiatric illness or social situation that would preclude study compliance
• No insulin-dependent diabetes mellitus
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No prior mediastinal radiation

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior nephrectomy

Other:

• No more than 2 prior systemic therapies for metastatic renal cell carcinoma
• No other concurrent investigational agents