UCN-01 and Cisplatin in Treating Patients With Advanced or Metastatic Solid Tumors

Phase I Dose Escalation Study of UCN-01 (NSC 638850) Plus Cisplatin in Advanced Malignant Solid Tumors

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of UCN-01 and cisplatin in treating patients who have advanced or metastatic solid tumors.

OBJECTIVES:

• Determine the maximum tolerated dose of cisplatin when administered with UCN-01 in patients with advanced solid tumors.
• Assess the toxicity and potential antitumor activity of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study of cisplatin.

Patients receive cisplatin IV over 1 hour on day 1 and UCN-01 IV continuously over 36-72 hours beginning on day 2. Treatment continues every 4 weeks for a total of 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of cisplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 2-3 months for at least 1 year.

PROJECTED ACCRUAL: A total of 9-30 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced or metastatic solid tumor incurable by surgery or other standard therapy
• Tumor site accessible by biopsy
• No brain metastasis

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 4,500/mm3
• Absolute neutrophil count at least 2,000/mm3
• Platelet count at least 150,000/mm3

Hepatic:

• Bilirubin normal
• SGOT no greater than 2.5 times upper limit of normal

Renal:

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

Cardiovascular:

• No New York Heart Association class III or IV congestive heart failure

Other:

• No peripheral neuropathy greater than grade I
• No history of allergic reactions to diuretics or antiemetics (e.g., 5-HT3 antagonists) that would preclude study
• No other uncontrolled illness that would preclude study, including intolerance to vigorous hydration
• No medical, social, or psychological factors that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• No greater than 2 prior chemotherapy regimens
• Prior cisplatin allowed if cumulative dose no greater than 400 mg/m2

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• Recovered from any prior surgery

Other:

• At least 30 days since prior investigational drugs
• No other concurrent investigational drugs
• No other concurrent anticancer agents