UCN-01 and Topotecan in Treating Patients With Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cavity Cancer

OBJECTIVES:

• Determine the maximum tolerated dose and recommended phase II dose of UCN-01 and topotecan in patients with recurrent ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer.
• Determine the safety and tolerability of this regimen in these patients.
• Determine the relationship between clinical and pharmacokinetic effects of this regimen in these patients.

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

Patients receive UCN-01 IV over 3 hours on day 1 and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of UCN-01 and topotecan 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. Up to 12 additional ovarian epithelial cancer patients are then treated at the recommended phase II dose.

Patients are followed at 4 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 6-10 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed recurrent ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer
• Measurable disease outside of field of prior radiotherapy OR
• Progressive disease within field after radiotherapy
• Must have had no more than 2 prior chemotherapy regimens

• At least 1 prior regimen must have included a platinum agent (e.g., carboplatin or cisplatin)
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

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

Renal

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

Cardiovascular

• No coronary artery disease
• No symptomatic cardiac dysfunction
• No symptoms suggestive of coronary artery disease with evidence of cardiac pathology

Pulmonary

• No symptomatic pulmonary dysfunction

Other

• No prior allergic reaction attributed to compounds of similar chemical or biologic composition to UCN-01 or other agents used in this study
• No insulin-dependent diabetes mellitus
• No other uncontrolled concurrent illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 4 weeks since prior biologic therapy

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No prior topotecan (other prior topoisomerase I inhibitors allowed)

Endocrine therapy

• At least 4 weeks since prior hormonal therapy

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No prior radiotherapy to more than 40% of bone marrow
• No prior mediastinal irradiation

Surgery

• At least 4 weeks since prior surgery

Other

• Recovered from all prior therapy
• No other concurrent investigational agents
• No other concurrent anticancer agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients