UCN-01 and Prednisone in Treating Patients With Solid Tumors or Lymphoma

OBJECTIVES:

• Determine the maximum tolerated dose of UCN-01 in combination with prednisone in patients with refractory solid tumors or lymphomas.
• Determine the toxic effects of this regimen in these patients.
• Assess the pharmacokinetics of this regimen in these patients.
• Assess any tumor response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of UCN-01.

Patients receive oral prednisone daily on days 1-5 and UCN-01 IV over 36-72 hours on days 3-5. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of UCN-01 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the recommended phase II dose.

Patients are followed every 3-12 months for 5 years.

PROJECTED ACCRUAL: Approximately 24 patients will be accrued for this study within 18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor or lymphoma

• Progressive disease after standard therapy
• No other therapy is likely to improve survival
• Prostate cancer patients must have progressed through hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists and withdrawal of testosterone receptor antagonists

• Patients must continue on GnRH agonist during study (if orchiectomy has not been performed) and have castrate testosterone levels
• Brain metastases allowed if treated and the patient has been stable off anti-seizure medication or steroids for > 6 months
• No local complications from disease requiring urgent therapy (i.e., hydronephrosis, spinal cord compression, or severe pain requiring improved pain management)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 100,000/mm^3
• 12-hour fasting glucose no greater than 110 mg/dL OR
• 12-hour fasting glucose no greater than 140 mg/dL with hemoglobin A1C no greater than 6.5 mg/dL

Hepatic

• PT/PTT no greater than 1.5 times upper limit of normal (ULN)
• Bilirubin no greater than 1.5 times ULN (unless Gilbert's syndrome present)
• AST/ALT no greater than 2.5 times ULN

Renal

• Creatinine clearance greater than 60 mL/min OR
• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris

Pulmonary

• No interstitial lung disease within the past year
• No requirement for oxygen therapy for hypoxia in the past 6 months

Gastrointestinal

• No diagnosis of duodenal or gastric ulcer
• No severe gastritis within the past 6 months

Other

• HIV negative
• No prior allergic reactions to other indolocarbazoles
• No diabetes or hyperglycemia within the past year that required a diabetic diet, oral hypoglycemics, or insulin
• No other uncontrolled illness
• No active infection
• No seizure disorder
• No psychiatric illness that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior UCN-01

Endocrine therapy

• See Disease Characteristics
• No other concurrent oral or IV steroids

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered

Surgery

• See Disease Characteristics
• At least 21 days since prior major surgery

Other

• See Disease Characteristics
• At least 4 weeks since prior investigational agents
• No other concurrent anticancer therapy