Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of topotecan combined with carboplatin and paclitaxel in treating patients who have stage II, stage III, or stage IV ovarian cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose, dose-limiting toxicity, and quantitative and qualitative toxic effects of oral topotecan combined with intravenous carboplatin and paclitaxel in patients with stage IIB, IIC, III, or IV ovarian epithelial cancer. (phase I closed to accrual 12/21/00) Evaluate the anti-tumor activity of this regimen in this patient population. OUTLINE: This is a multicenter, dose-escalation study of topotecan. Patients receive oral topotecan on days 1-5 and paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 5. Courses repeat every 21 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Phase I: Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity. (phase I closed to accrual 12/21/00) Phase II: An additional 50 patients receive up to 6 courses of treatment as in phase I at the MTD. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 80 patients (30 in phase I and 50 in phase II) will be accrued for this study. (phase I closed to accrual 12/21/00)

Official Title
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A Phase I/II Study to Determine the Maximum Tolerated Doses of Oral Topotecan, Carboplatin and Paclitaxel Administered Every 21 Days to Patients With Epithelial Ovarian Cancer Stages IIb, IIc, III and IV

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: paclitaxel
* Drug: topotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage IIB, IIC, III, or IV ovarian epithelial cancer Measurable or evaluable lesion or microscopic residual disease after first surgery (phase II patients) No brain and/or leptomeningeal metastases by CT scan or MRI unless asymptomatic without corticosteroid therapy PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: Hemoglobin at least 9.0 g/dL WBC at least 3,500/mm3 Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) unless liver metastases present Alkaline phosphatase no greater than 2 times ULN* SGOT no greater than 2 times ULN* NOTE: *No greater than 5 times ULN if liver metastases present Renal: Creatinine no greater than 1.5 times ULN Creatinine clearance at least 60 mL/min Cardiovascular: No symptomatic cardiac disease, including clinical congestive heart failure or arrhythmias requiring treatment No myocardial infarction within the past 3 months Other: No other malignancy except basal or squamous cell skin cancer or carcinoma in situ of the cervix No uncontrolled infection No complete bowel obstruction or other condition that would affect GI absorption or motility No concurrent medical condition for which treatment with platinum, taxane, or camptothecin analogues are contraindicated No other concurrent medical conditions that would preclude study No mental disease No history of allergy to platinum or taxanes, including drugs containing cremophor (e.g., cyclosporine or vitamin K) Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: No prior camptothecin analogue No prior chemotherapy for ovarian cancer No other concurrent chemotherapy Endocrine therapy: See Disease Characteristics No concurrent hormonal therapy other than estrogen replacement Radiotherapy: No concurrent radiotherapy Surgery: See Disease Characteristics Other: At least 30 days or 5 half-lives since any prior investigational therapy No other concurrent investigational therapy No concurrent metoclopramide or cisapride

Ages Eligible for Study
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Minimum Age: 18 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carboplatin|nan|
|Drug: paclitaxel|nan|
|Drug: topotecan hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose and dose-limiting toxicity of topotecan |  |  | 
| Toxic effects |  |  | 
| Antitumor activity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIB ovarian epithelial cancer, stage IIC ovarian epithelial cancer, stage IIIA ovarian epithelial cancer, stage IIIB ovarian epithelial cancer, stage IIIC ovarian epithelial cancer, stage IV ovarian epithelial cancer