S0200 Carboplatin With or Without Doxil in Patients With Recurrent Ovarian 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 may kill more tumor cells. It is not yet known if carboplatin is more effective with or without liposomal doxorubicin in treating recurrent ovarian epithelial or primary peritoneal cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of carboplatin with or without liposomal doxorubicin in treating patients who have recurrent ovarian epithelial or primary peritoneal cancer.

Detailed Description
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OBJECTIVES: Compare overall survival of patients with platinum-sensitive recurrent ovarian epithelial or primary peritoneal cancer treated with carboplatin with or without pegylated doxorubicin HCl liposome. Compare progression-free survival, confirmed complete response rates, and time to treatment failure in patients treated with these regimens. Compare the toxicity of these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease measurability (elevated CA 125 only vs nonmeasurable disease only with or without elevated CA 125 vs measurable disease), number of disease sites (2 or fewer vs 3 or more), and serous tumor histology (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive carboplatin IV over 15 minutes and pegylated doxorubicin HCl liposome IV over 1 hour on day 1. Arm II: Patients receive carboplatin IV as in arm I. Treatment in both arms repeats every 4 weeks for a total of 15 courses in the absence of disease progression or unacceptable toxicity. Patients are followed at 4 weeks, every 6 months for 3 years, and then annually for 7 years. PROJECTED ACCRUAL: A total of 900 patients will be accrued for this study within 4 years.

Official Title
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A Phase III Study of Liposomal Doxorubicin Plus Carboplatin Versus Carboplatin in Platinum-Sensitive Patients With Recurrent Epithelial Ovarian and Peritoneal Carcinoma After Failure of Initial Platinum-Based Chemotherapy

Conditions
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Ovarian Cancer, Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: pegylated liposomal doxorubicin hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed ovarian epithelial carcinoma Stage III or IV disease at time of initial staging laparotomy Primary peritoneal and mixed Mullerian tumors allowed No borderline ovarian tumors Disease progression or recurrence after a progression-free and platinum-free interval of 6-24 months after completion of first-line platinum-based chemotherapy (either single agent or combination therapy) Disease progression or recurrence based solely on CA 125 elevation allowed, provided that one of the following is true: Prior baseline CA 125 greater than 35 U/mL and subsequent normalization of no greater than 35 U/mL must have CA 125 greater than 2 times upper limit of normal (ULN) on 2 occasions at least 1 week apart Prior baseline CA 125 greater than 35 U/mL that never normalized must have CA 125 greater than 2 times the nadir value on 2 occasions at least 1 week apart Prior normal baseline CA 125 (no greater than 35 U/mL) must show CA 125 greater than 2 times ULN on 2 occasions at least 1 week apart No known brain metastases PATIENT CHARACTERISTICS: Age Not specified Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL Hepatic SGOT and/or SGPT no greater than 2 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2 times ULN Bilirubin no greater than ULN Renal Creatinine no greater than 1.9 mg/dL Cardiovascular No New York Heart Association class II-IV cardiac disease No clinical evidence of congestive heart failure Ejection fraction greater than 50% by MUGA or 2-dimensional echocardiogram Other Not pregnant or nursing Fertile patients must use effective contraception No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or incidental carcinoid cancer No evidence of active or uncontrolled infection No severe gastrointestinal symptoms (i.e., partial obstruction) and/or gastrointestinal bleeding or diarrhea No greater than grade 1 preexisting sensory neuropathy PRIOR CONCURRENT THERAPY: Biologic therapy At least 28 days since prior biologic consolidation therapy No concurrent immunotherapy Chemotherapy See Disease Characteristics At least 28 days since prior non-platinum-containing consolidation chemotherapy No prior pegylated doxorubicin HCl liposome No prior cumulative anthracycline (e.g., doxorubicin, daunorubicin, epirubicin) dose in excess of 240 mg/m^2 No other concurrent chemotherapy Endocrine therapy No concurrent hormonal therapy Radiotherapy No prior abdominopelvic irradiation No concurrent radiotherapy Surgery See Disease Characteristics At least 28 days since prior surgical debulking for disease progression or recurrence and recovered No concurrent surgery Other No other prior treatment during the 6-24 month progression-free and platinum-free interval except up to 12 courses of consolidation therapy No other concurrent anticancer therapy

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: carboplatin and doxorubicin<br>carboplatin and liposomal doxorubicin given q 4 weeks | Drug: carboplatin<br>* intravenous q 4 weeks<br>Drug: pegylated liposomal doxorubicin hydrochloride<br>* intravenous q 4 weeks<br>|
| Active Comparator: carboplatin<br>carboplatin alone | Drug: carboplatin<br>* intravenous q 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | From date of registration to date of death | ten years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival and response | response by RECIST criteria | 10 years | 
| side effects | side effects described per NCI CTC version 2.0 | 15 months | 

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