Combination Chemotherapy Regimens in Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube 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. Combining more than one drug and giving the drugs in different combinations may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating ovarian epithelial, primary peritoneal, or fallopian tube cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens in treating patients who have stage IIB, stage III, or stage IV ovarian epithelial cancer , primary peritoneal cancer, or fallopian tube cancer.

Detailed Description
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OBJECTIVES: Compare the efficacy of cisplatin and topotecan followed by paclitaxel and carboplatin vs paclitaxel and carboplatin only, in terms of time to disease progression, in patients with newly diagnosed stage IIB-IV ovarian epithelial, primary peritoneal, or fallopian tube cancer. Compare the overall survival of patients treated with these regimens. Compare the clinical objective response rates in patients with measurable disease at baseline treated with these regimens. Compare the toxic effects of these regimens in these patients. Compare the CA 125 normalization rates in patients treated with these regimens. Compare the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, age (65 years and under vs over 65 years), and pre-randomization surgery (no debulking vs debulking with macroscopic residual disease less than 1 cm vs debulking with macroscopic residual disease 1 cm or greater vs debulking with no macroscopic residual disease). Patients are randomized to one of two treatment arms. Arm I: Patients receive cisplatin IV over 60 minutes on day 1 and topotecan IV over 30 minutes on days 1-5 of courses 1-4 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 of courses 5-8. Arm II: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 of courses 1-8. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Planned interval debulking surgery should occur after course 3 or 4. Quality of life is assessed at baseline; on day 1 of courses 3, 5, and 7; at the end of the last course; and at 3 and 6 months after study treatment completion. Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 800 patients (400 per treatment arm) will be accrued for this study within 2 years.

Official Title
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A Phase III Study of Cisplatin Plus Topotecan Followed by Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Carboplatin as First Line Chemotherapy in Women With Newly Diagnosed Advanced Epithelial Ovarian Cancer

Conditions
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Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage IIB-IV ovarian epithelial, primary peritoneal, or fallopian tube cancer No borderline ovarian tumors Residual disease allowed Fine needle aspiration showing an adenocarcinoma is allowed instead of open or true-cut biopsy if the following are true: Presence of pelvic mass AND Omental cake or other metastasis larger than 2 cm in the upper abdomen unless proven stage IV disease AND Serum CA 125/carcinoembryonic antigen ratio at least 25 (if less than 25, a barium enema or colonoscopy and gastroscopy or radiological examination of the stomach should be negative for primary tumor within 6 weeks of study) AND Normal mammography within 6 weeks of study PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: ECOG 0-1 Life expectancy: At least 12 weeks Hematopoietic: Granulocyte count at least 2,000/mm^3 Platelet count at least 150,000/mm^3 Hepatic: Not specified Renal: Creatinine no greater than upper limit of normal Cardiovascular: No clinically relevant atrial or ventricular arrhythmias No myocardial infarction (MI) within the past 6 months (pretreatment ECG as only evidence of MI allowed) No history of second- or third-degree heart blocks unless pacemaker implanted History of first-degree heart block allowed Other: Not pregnant or nursing Fertile patients must use effective contraception No complete bowel obstruction No prior allergic reaction to drugs containing Cremophor EL or compounds chemically related to study drugs No condition that would preclude high-volume saline diuresis No significant neurologic or psychiatric disorder that would preclude study compliance No active uncontrolled infection No neuropathy greater than grade 1 No pre-existing hearing loss greater than grade 1 No other concurrent serious illness or medical condition that would preclude study participation No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent biological response modifiers or immunotherapy No concurrent prophylactic colony-stimulating factors (CSFs) Concurrent therapeutic CSFs allowed Chemotherapy: No prior chemotherapy for ovarian cancer No other concurrent cytotoxic agents Endocrine therapy: No concurrent anticancer hormonal therapy Radiotherapy: No prior radiotherapy for ovarian cancer Surgery: No more than 6 weeks since prior planned pre-chemotherapy surgery for ovarian cancer Planned interval debulking allowed Concurrent second-look surgery allowed Other: No prior non-surgical therapy for ovarian cancer No other concurrent investigational drug therapy No other concurrent anticancer treatment Concurrent enrollment on CAN-NCIC-OV13/EORTC 55971 allowed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cisplatin, Topotecan, Paclitaxel plus Carboplatin<br>Arm 1 | Drug: carboplatin<br>* Arm 1 = 4 cycles vs Arm 2 = 8 cycles AUC5 (30 mins) day 1 of 21 day cycle<br>Drug: cisplatin<br>* 4 cycles 50mg/m2 (60 mins) day 1 of 21 day cycle<br>Drug: paclitaxel<br>* Arm 1 = 4 cycles vs Arm 2 = 8 cycles 175mg/m2 (3 hours) day 1 of 21 day cycle<br>Drug: topotecan hydrochloride<br>* 4 cycles .75mg/m2 (30 mins) days 1-5 of 21 day cycle<br>|
| Active Comparator: Paclitaxel plus Carboplatin<br>Arm 2 | Drug: carboplatin<br>* Arm 1 = 4 cycles vs Arm 2 = 8 cycles AUC5 (30 mins) day 1 of 21 day cycle<br>Drug: paclitaxel<br>* Arm 1 = 4 cycles vs Arm 2 = 8 cycles 175mg/m2 (3 hours) day 1 of 21 day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | Mar 2008 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | Dec 2012 | 
| Response Rates |  | March 2008 | 
| Toxic Effects |  | March 2008 | 
| Quality of Life |  | March 2008 | 
| CA125 Normalization Rates |  | March 2008 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, fallopian tube cancer, peritoneal cavity cancer