TC or BEP in Treating Patients With Malignant Ovarian Germ Cell Tumors

Study Overview
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Brief Summary
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Investigators will conduct the trial to determine whether paclitaxel and cisplatin (PT) has the same curative effects and less adverse effects than bleomycin, etoposide and cisplatin(BEP) among newly diagnosed malignant ovarian germ cell tumor patients after surgery.

Detailed Description
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PRIMARY OBJECTIVES: To assess the activity of paclitaxel and carboplatin with respect to progression free survival (using bleomycin, etoposide, and cisplatin [BEP] as a reference) for newly diagnosed malignant ovarian germ cell tumors. SECONDARY OBJECTIVES: To estimate the toxicity of paclitaxel and carboplatin, and bleomycin, etoposide, and cisplatin in this patient population. To estimate overall survival for paclitaxel and carboplatin relative to that of BEP. To evaluate response rate in the subset of patients with measurable disease. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. ARM 1: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. ARM 2: Patients receive bleomycin IM daily for days 1-3, etoposide IV daily for days 1-5, cisplatin IV for days 1-5. Treatment repeats every 21 days for 3 or 4* courses in the absence of disease progression or unacceptable toxicity. NOTE: *Patients who have good risk will have 3 courses and those who have poor risks will have 4 courses. Patients undergo blood sample collection at baseline and periodically during study for laboratory biomarker analysis. After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Official Title
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A Multicenter, Prospective, Randomized Trial Comparing Paclitaxel and Carboplatin or Bleomycin, Etoposide and Cisplatin in the Treatment of Malignant Ovarian Germ Cell Tumors

Conditions
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Ovarian Germ Cell Cancer, Ovarian Neoplasms, Ovarian Cancer

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: Bleomycin
* Drug: Etoposide
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≤65 years; female, Chinese women; Histologically confirmed ovarian stromal tumor, including the following cell types: Granulosa cell tumor Granulosa cell-theca cell tumor Sertoli-Leydig cell tumor (androblastoma) Steroid (lipid) cell tumor Gynandroblastoma Unclassified sex cord-stromal tumor Sex cord tumor with annular tubules Newly diagnosed, stage IIA-IVB disease; Has undergone initial surgery (for diagnosis, staging, or cytoreduction) within the past 8 weeks. May or may not have measurable residual disease. Laboratory tests: WBC≥4×10(9)/L, NEU≥2×10(9)/L, PLT≥80×10(9)/L, serum bilirubin≤ 1.5 times the upper limit of normal, transaminase≤ 1.5 times the upper limit of normal, BUN, Cr≤ normal Performance status: Karnofsky score≥60; Provide written informed consent. Exclusion Criteria: With severe or uncontrolled internal disease, unable to receive surgery and/or unsuitable for chemotherapy; History of organ transplantation, immune diseases; History of serious mental illness, a history of brain dysfunction; Drug abuse or a history of drug abuse; Suffering from other malignancies; Concurrently participating in other clinical trials Unable or unwilling to sign informed consents; Unable or unwilling to abide by protocol.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 65 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: PT (Arm 1)<br>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. | Drug: Paclitaxel<br>* Patients receive paclitaxel 175mg/㎡ IV over 3 hours on day 1. Treatment repeats every 21 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.<br>* Other names: TAX;Drug: Carboplatin<br>* and carboplatin AUC 5-6 IV over 1 hour on day 1. Treatment repeats every 21 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.<br>|
| Active Comparator: BEP (Arm 2)<br>Patients receive bleomycin IM daily for days 1-3, etoposide IV daily for days 1-5, cisplatin IV for days 1-5. Treatment repeats every 21 days for 3 or 4* courses in the absence of disease progression or unacceptable toxicity. NOTE: *Patients who have good risk will have 3 courses and those who have poor risks will have 4 courses. | Drug: Bleomycin<br>* Bleomycin 30000IU IM per day for 3 days every 3 weeks for 3-4 cycles.<br>* Other names: BLM;Drug: Etoposide<br>* Etoposide 100mg/㎡ IV per day for 5 days every 3 weeks for 3-4 cycles.<br>* Other names: Etopophos;Drug: Cisplatin<br>* Cisplatin 20mg/㎡ IV per day for 5 days every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | PFS was definite as the time from randomization to disease recurrence (including death from recurrence if it was the first manifestation of recurrence), death without recurrence. | Date of randomization, and death due to any cause, assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chemotherapy related adverse effects in two arms |  | Up to 5 years | 
| Tumor response rate | The relationship of treatment to tumor response rate will be assessed using logistic regression models adjusted for age and stratification factor (measurable disease status). | Up to 5 years | 
| Overall survival | The relationship of treatment to overall survival will be assessed using the proportional hazards model. | Up to 5 years |