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 which chemotherapy regimen is most effective for ovarian epithelial cancer.

PURPOSE: This randomized phase III trial is studying high-dose chemotherapy to see how well it works compared to standard chemotherapy in treating patients with stage III or stage IV ovarian epithelial cancer that has been removed during surgery.

Condition	Treatment or Intervention	Phase
stage III ovarian epithelial cancer stage IV ovarian epithelial cancer	Drug: carboplatin  Drug: cyclophosphamide  Drug: filgrastim  Drug: melphalan  Drug: paclitaxel  Procedure: adjuvant therapy  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: high-dose chemotherapy  Procedure: peripheral blood stem cell transplantation	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the two-year progression-free survival in patients with optimally debulked stage III or IV ovarian epithelial cancer undergoing high-dose sequential chemotherapy vs standard chemotherapy.
• Compare the overall survival, toxicity, and quality of life in this patient population receiving these two treatment regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Patients receive 5 courses of sequential high-dose chemotherapy as follows:
• Courses 1 and 2: Patients receive paclitaxel IV over 3 hours and cyclophosphamide IV over 2 hours on day 1 followed by peripheral blood stem cell (PBSC) collection. Patients receive filgrastim (G-CSF) subcutaneously (SC) beginning 24 hours following chemotherapy and continuing until target number of PBSC are reached.
• Courses 3 and 4: Patients receive paclitaxel as in courses 1-2 and carboplatin IV over 4 hours on day 1. At 72 hours following completion of carboplatin, patients receive PBSC infusion. Beginning one day following PBSC infusion, patients receive G-CSF SC until blood counts recover.
• Course 5: Patients receive paclitaxel as in courses 1 and 2 and carboplatin as in courses 3 and 4 and melphalan IV over 15 minutes on day 2 or 3. Patients receive PBSC and G-CSF as in courses 3 and 4.
• Treatment repeats every 3-4 weeks.
• Arm II: Patients receive standard chemotherapy consisting of carboplatin (or cisplatin) and paclitaxel IV over 3 hours every 3 weeks for 6 courses. Patients may receive doxorubicin or epirubicin in addition to the standard chemotherapy every 4 weeks. Quality of life is assessed prior to therapy, at 4-6 weeks following completion of therapy, and then at 3 months, 9 months, and 15 months.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 208 patients (104 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage III or IV ovarian epithelial cancer
• Bilateral salpingo-oophorectomy, hysterectomy, and omentectomy within 6 weeks of study
• Less than 2 cm maximum diameter of residual tumor remaining

PATIENT CHARACTERISTICS: Age:

• 18 to 65

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Normal hematological function

Hepatic:

• Normal hepatic function

Renal:

• Creatinine clearance greater than 60 mL/min
• GFR greater than 60 mL/min

Cardiovascular:

• No active cardiac disease

Other:

• No other uncontrolled serious medical illness, including hearing problems
• No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics

Austria
      Sozialmedizinisches Zentrum Ost - Donauspital, Vienna,  A-1220,  Austria; Recruiting
Belgium
      Centre Hospitalier Notre Dame - Reine Fabiola, Charleroi,  6000,  Belgium; Recruiting
Czech Republic
      Charles University, Prague 10,  10034,  Czech Republic; Recruiting
      Thomayer Memorial Teaching Hospital, PRAGUE 4,  14000,  Czech Republic; Recruiting
Germany
      Klinikum Nuernberg - Klinikum Nord, Nuernberg,  D-90419,  Germany; Recruiting
      Staedt Klinikum Karlsruhe GGMBH, Karlsruhe,  76133,  Germany; Recruiting
Italy
      Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi, Bologna,  40138,  Italy; Recruiting
      Ospedale San Bortolo, Vicenza,  36100,  Italy; Recruiting
      Ospedale Santa Chiara, Pisa,  56100,  Italy; Recruiting
      S. Camillo Hospital, Rome,  00152,  Italy; Recruiting
Slovakia
      National Cancer Institute - Bratislava, Bratislava,  833 10,  Slovakia; Recruiting
Spain
      Hospital Clinico Universitario de Valencia, Valencia,  46010,  Spain; Recruiting
      Hospital Universitario San Carlos, Madrid,  28040,  Spain; Recruiting
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland; Recruiting
United Kingdom, England
      Cancer Research Centre at Weston Park Hospital, Manchester,  England,  M20 9BX,  United Kingdom; Recruiting
      Cancer Research UK and University College London Cancer Trials Centre, London,  England,  NW1 2ND,  United Kingdom; Recruiting
      St. James's University Hospital at Leeds Teaching Hospital NHS Trust, Leeds,  England,  LS9 7TF,  United Kingdom; Recruiting

Study chairs or principal investigators

Jonathan A. Ledermann, MD,  Study Chair,  Cancer Research UK   

Study ID Numbers:  CDR0000067604; EBMT-HIDOC-EIS; EBMT-OVCAT; EU-99040; NCT00004921
Record last reviewed:  October 2003
Last Updated:  April 4, 2005
Record first received:  March 7, 2000
ClinicalTrials.gov Identifier:  NCT00004921
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08