Combination Chemotherapy in Treating Patients With Stage III or Stage IV Ovarian Epithelial Cancer or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is most effective in treating ovarian epithelial cancer and peritoneal cancer. Randomized phase III trial to compare the effectiveness of various combination chemotherapy regimens in treating patients who have stage III or stage IV ovarian cancer or primary peritoneal cancer.

Detailed Description
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OBJECTIVES: Compare the efficacy of paclitaxel and carboplatin with or without gemcitabine, doxorubicin HCl liposome, or topotecan, in terms of overall and progression-free survival, in patients with stage III or IV ovarian epithelial or serous primary peritoneal carcinoma. Determine the response rate in patients with measurable disease treated with these regimens. Compare the toxic effects of these regimens in these patients. Compare the complications in patients treated with these regimens. Determine the dose-intensity and cumulative dose delivery for these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified into 1 of 3 strata according to extent of residual disease and plans for interval cytoreductive surgery: Stratum A: Optimal (microscopic or macroscopic) residual disease without plans for surgery Stratum B: Suboptimal residual disease without plans for surgery Stratum C: Suboptimal residual disease with plans for surgeryPatients are randomized to 1 of 5 treatment arms. Arm I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment continues every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive chemotherapy as in arm I and gemcitabine IV over 30 minutes on days 1 and 8. Treatment continues as in arm I. Arm III: Patients receive chemotherapy as in arm I during courses 1-8 and doxorubicin HCl liposome IV over 1 hour on day 1 during courses 1, 3, 5, and 7. Treatment continues as in arm I. Arm IV: Patients receive topotecan IV over 30 minutes on days 1-3 and carboplatin IV over 30 minutes on day 3. Treatment continues every 3 weeks for 4 courses. Patients then receive 4 courses of arm I chemotherapy. Arm V: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 8. Treatment continues every 3 weeks for 4 courses. Patients then receive 4 courses of arm I chemotherapy. Patients with initial unresectable or suboptimal residual disease (more than 1 cm) may undergo interval cytoreductive surgery between courses 4 and 5 of chemotherapy. Patients are followed every 3 months for 2 years and then every 6 months. PROJECTED ACCRUAL: Approximately 4,000-5,000 patients (800-1,000 per treatment arm) will be accrued for this study within 3.5-5 years.

Official Title
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A Phase III Randomized Trial Of Paclitaxel And Carboplatin Versus Triplet Or Sequential Doublet Combinations In Patients With Epithelial Ovarian Or Primary Peritoneal Carcinoma

Conditions
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Primary Peritoneal Carcinoma, Stage III Ovarian Cancer, Stage IV Ovarian Cancer

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: Gemcitabine Hydrochloride
* Drug: Pegylated Liposomal Doxorubicin Hydrochloride
* Drug: Topotecan Hydrochloride
* Procedure: Therapeutic Conventional Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed stage III or IV ovarian epithelial or serous primaryperitoneal carcinoma The following are ineligible: Germ cell tumors Sex cord-stromal tumors Carcinosarcomas Mixed Mullerian tumors or carcinosarcomas Metastatic carcinomas from other sites to theovary Low malignant potential tumors, including micropapillary serouscarcinomas Mucinous primary peritoneal carcinoma Prior ovarian low malignant potential tumor (borderline carcinoma) that was surgically resected with subsequent development of invasive adenocarcinoma allowed if no prior chemotherapy Optimal (no greater than 1 cm) or suboptimal residual disease after initial surgery Prior breast cancer allowed provided the following are true: Disease-free for more than 5 years No prior cytotoxic chemotherapy for breast cancer Prior or concurrent primary endometrial cancer allowed if the following conditions are met: Stage no greater than IB Less than 3 mm invasion without vascular or lymphatic invasion No poorly differentiated subtypes, including papillary serous, clear cell, or other FIGO grade 3 lesions Performance status - GOG 0-2 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN No acute hepatitis Creatinine no greater than 1.5 times ULN No unstable angina No myocardial infarction within the past 6 months No evidence of abnormal cardiac conduction (e.g., bundle branch block, heart block) unless stable for the past 6 months Not pregnant or nursing Fertile patients must use effective contraception No greater than grade 1 sensory or motor neuropathy No active infection that requires antibiotics No other invasive malignancy within the past 5 years except nonmelanoma skin cancer No severe or ongoing gastrointestinal bleeding that requires blood product support See Disease Characteristics Prior chemotherapy for cancer involving the abdominal cavity or pelvis allowed provided the following are true: More than 3 years since prior therapy No evidence of recurrent disease No prior radiotherapy to any portion of the abdominal cavity or pelvis Prior radiotherapy for localized breast, head and neck, or skin cancer allowed provided the following are true: More than 3 years since prior therapy No evidence of recurrent disease See Disease Characteristics No more than 12 weeks since prior surgical resection
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: Arm I<br>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment continues every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. | Drug: Paclitaxel<br>* Given IV<br>* Other names: TAX;Drug: Carboplatin<br>* Given IV<br>|
| Experimental: Arm II<br>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. | Drug: Paclitaxel<br>* Given IV<br>* Other names: TAX;Drug: Carboplatin<br>* Given IV<br>Drug: Gemcitabine Hydrochloride<br>* Given IV<br>* Other names: dFdCyd;|
| Experimental: Arm III<br>Patients receive chemotherapy as in arm I during courses 1-8 and doxorubicin HCl liposome IV over 1 hour on day 1 during courses 1, 3, 5, and 7. Treatment continues as in arm I. | Drug: Paclitaxel<br>* Given IV<br>* Other names: TAX;Drug: Carboplatin<br>* Given IV<br>Drug: Pegylated Liposomal Doxorubicin Hydrochloride<br> <br> * Other names: TLC D-99;|
| Experimental: Arm IV<br>Patients receive topotecan IV over 30 minutes on days 1-3 and carboplatin IV over 30 minutes on day 3. Treatment continues every 3 weeks for 4 courses. Patients then receive 4 courses of arm I chemotherapy. | Drug: Paclitaxel<br>* Given IV<br>* Other names: TAX;Drug: Carboplatin<br>* Given IV<br>Drug: Topotecan Hydrochloride<br>* Given IV<br>* Other names: TOPO;|
| Experimental: Arm V<br>Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 8. Treatment continues every 3 weeks for 4 courses. Patients then receive 4 courses of arm I chemotherapy. Patients with initial unresectable or suboptimal residual disease (more than 1 cm) may undergo interval cytoreductive surgery between courses 4 and 5 of chemotherapy. | Drug: Paclitaxel<br>* Given IV<br>* Other names: TAX;Drug: Carboplatin<br>* Given IV<br>Drug: Gemcitabine Hydrochloride<br>* Given IV<br>* Other names: dFdCyd;Procedure: Therapeutic Conventional Surgery<br>* Undergo surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Proportion of participants whose overall survival exceeded 5 years. | Up to 9 years | 
| Progression-free Survival | Median duration in months of progression free survival. | From the date of enrollment to first progression or death or last contact, if alive and progression free. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Observed Adverse Effects (Grade 3 and Above) Assessed by Common Toxicity Criteria Version 2.0 |  | Up to 9 years |