Phase III Multicenter Study in Epithelial Ovarian Carcinoma FIGO Stage IIB-IV Comparing Treatment With Paclitaxel and Carboplatin to Paclitaxel and Carboplatin Sequentially Followed by Topotecan
Phase III Multicenter Study in Epithelial Ovarian Carcinoma FIGO Stage IIB-IV Comparing Treatment With Paclitaxel and Carboplatin to Paclitaxel and Carboplatin Sequentially Followed by Topotecan
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. It is not yet known if paclitaxel plus carboplatin is more effective with or without topotecan for ovarian epithelial cancer.
PURPOSE: Randomized phase III trial to compare the effectiveness of paclitaxel plus carboplatin with or without topotecan in treating patients who have stage IIB, stage III, or stage IV ovarian epithelial cancer.
OBJECTIVES: I. Compare survival of patients with stage IIB, III, or IV ovarian epithelial carcinoma after receiving treatment with paclitaxel and carboplatin with or without topotecan. II. Compare progression-free survival of these patients after receiving these treatment regimens. III. Compare the response rate and response duration in these patients treated with these regimens. IV. Determine the toxic effects of the combination of paclitaxel, carboplatin, and topotecan in these patients. V. Compare the toxic effects of these treatment regimens in these patients. VI. Compare quality of life of these patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and stage (stage IIB and stage III optimally debulked to no greater than 1 cm residual tumor vs stage IV regardless of residual tumor or residual tumor greater than 1 cm). Patients are randomized to one of two treatment arms. Arm I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 0.5-1 hour on day 1 and topotecan IV over 0.5 hour on days 1-5. Treatment repeats every 21 days for 6 courses (topotecan is administered for 4 courses only). Arm II: Patients receive paclitaxel and carboplatin as in arm I. Treatment repeats every 21 days for 6 courses. Quality of life is assessed before courses 1, 3, and 5 and at 3 weeks and 3 months after completion of treatment in both treatment arms; before courses 1 and 3 of topotecan in arm I; and at 6 months after completion of treatment in arm II. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 914 patients (457 per treatment arm) will be accrued for this study over 2 years.
DISEASE CHARACTERISTICS: Histologically confirmed stage IIB, III, or IV ovarian epithelial carcinoma, fallopian tube, or extraovarian papillary serous carcinoma extending to the ovary No mixed epithelial/non-epithelial tumors (e.g., mixed Mullerian tumors) No tumors of low malignant potential (e.g., borderline tumors) No symptomatic brain metastases
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 OR Karnofsky 70-100% Life expectancy: More than 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times the upper limit of normal (ULN) Alkaline phosphatase no greater than 3 times ULN Renal: Creatinine no greater than 1.25 times ULN Estimated glomerular filtration rate at least 60 mL/min Cardiovascular: No history of congestive heart failure (even if medically controlled) No New York Heart Association class III or IV heart disease No myocardial infarction within the past 6 months No history of atrial or ventricular arrhythmias Other: No motor or sensory neurologic pathology or symptoms greater than grade 1 No active infection or other serious medical condition that would preclude study No prior allergy to drug containing Cremophor EL No dementia or significantly altered mental state that would preclude informed consent No complete bowel obstruction No other prior malignancy except curatively treated nonmelanomatous skin cancer or carcinoma in situ of the cervix Not pregnant or nursing Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy No concurrent WBC transfusions Chemotherapy: No prior chemotherapy No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy Radiotherapy: No prior radiotherapy No concurrent radiotherapy Surgery: No more than 6 weeks since prior definitive laparotomy and recovered Other: No other concurrent antineoplastic agents No other concurrent investigational drugs
Greifswald, D-17487, Germany