Doxorubicin and Cisplatin With or Without Paclitaxel in Treating Patients With Locally Advanced, Metastatic, and/or Relapsed Endometrial Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in 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 whether doxorubicin and cisplatin are more effective with or without paclitaxel in treating endometrial cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of combining doxorubicin and cisplatin with or without paclitaxel in treating patients who have locally advanced, metastatic, and/or relapsed endometrial cancer.

Detailed Description
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OBJECTIVES: Compare the overall survival of patients with locally advanced, metastatic, and/or relapsed endometrial cancer treated with doxorubicin and cisplatin with or without paclitaxel. Compare the toxicity of these regimens in these patients. Compare the progression-free survival at 18 months of patients treated with these regimens. Compare quality of life of patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to performance status (0 vs 1 vs 2), metastatic disease (M0 vs M1), prior pelvic radiotherapy for pelvic recurrence (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive doxorubicin IV over 30 minutes, paclitaxel IV over 3 hours, and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive doxorubicin and cisplatin as in arm I. Quality of life is assessed at baseline, before each course, after courses 3 and 6, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. In the event of progressive disease, quality of life is assessed every 3 months. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. In the event of progressive disease, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 140 patients will be accrued for this study.

Official Title
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Randomized Trial Of Adriamycin (A) Cisplatin (P) Chemotherapy Versus Paclitaxel (T) Adriamycin (A) And Cisplatin (P) In Patients With Metastatic/Relapsed Or Locally Advanced Inoperable Endometrial Cancer

Conditions
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Endometrial Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: doxorubicin hydrochloride
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed endometrial epithelial carcinoma meeting at least 1 of the following criteria: Advanced metastatic and/or relapsed disease Locally advanced inoperable or unresectable disease No mixed mesodermal tumor and/or tumors showing evidence of sarcomatous elements Uterine papillary serous carcinoma allowed PATIENT CHARACTERISTICS: Age 18 and over Performance status WHO 0-2 Life expectancy Not specified Hematopoietic Neutrophil count greater than 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin greater than 10 g/dL (transfusions allowed) Hepatic ALT and AST less than 2 times upper limit of normal (ULN) Alkaline phosphatase less than 2 times ULN Bilirubin less than 1.5 times ULN Renal Creatinine less than 1.5 times ULN Creatinine clearance greater than 50 mL/min Cardiovascular Normal baseline EKG Normal baseline LVEF on MUGA or echocardiogram for patients who received prior anthracyclines Other Able to tolerate high-dose dexamethasone Must be considered fit for chemotherapy No uncontrolled infection No other malignancy within the past 5 years except successfully treated basal cell skin cancer or carcinoma in situ of the cervix No prior nervous or psychiatric disorder that would preclude study compliance No psychological, familial, sociological, or geographic condition that would preclude study participation Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy At least 12 months since prior adjuvant chemotherapy Total dose of prior doxorubicin no greater than 200 mg/m^2 Total dose of prior epirubicin no greater than 300 mg/m^2 Endocrine therapy At least 28 days since prior hormonal therapy for patients with partial or complete response after first-line treatment Radiotherapy No prior radiotherapy to any area other than pelvis No concurrent radiotherapy Surgery Not specified Other No other concurrent anticancer medications

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
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: paclitaxel|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival as measured by Kaplan Meier and RECIST at 18 months |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival as measured by Kaplan Meier after each course, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter |  |  | 
| Toxicity as measured by NCIC Common Toxicity Criteria v2.0 after each course |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent endometrial carcinoma, stage III endometrial carcinoma, stage IV endometrial carcinoma, endometrial papillary serous carcinoma