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

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Topotecan may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining chemotherapy with topotecan may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining UCN-01 with topotecan in treating patients who have recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cavity cancer.

Detailed Description
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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.

Official Title
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A Phase I Study of UCN-01 in Combination With Topotecan in Patients With Solid Tumors

Conditions
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Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: 7-hydroxystaurosporine
* Drug: topotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UCN-01 in combination with topotecan<br> | Drug: 7-hydroxystaurosporine<br> <br> Drug: topotecan hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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primary peritoneal cavity cancer, recurrent ovarian epithelial cancer, fallopian tube cancer