RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether receiving paclitaxel and carboplatin with epirubicin is more effective than paclitaxel and carboplatin alone for ovarian epithelial, fallopian tube, or peritoneal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of paclitaxel and carboplatin with or without epirubicin in treating patients who have stage IIB, stage III, or stage IV invasive ovarian epithelial, fallopian tube, or peritoneal cancer.

Condition	Treatment or Intervention	Phase
stage II ovarian epithelial cancer stage III ovarian epithelial cancer stage IV ovarian epithelial cancer Fallopian Tube Cancer peritoneal cavity cancer	Drug: carboplatin  Drug: epirubicin  Drug: paclitaxel  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: surgery	Phase III

Further Study Details: 

OBJECTIVES:

• Compare progression free survival and overall survival in patients with stage IIB, III, or IV invasive ovarian epithelial, fallopian tube, or peritoneal cancer treated with paclitaxel and carboplatin with or without epirubicin.
• Compare the toxicity of these 2 regimens in these patients.
• Compare the quality of life of patients treated with these 2 regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by center and type of surgery (delayed surgery: 3 courses of chemotherapy before surgery vs primary surgery: optimally debulked stage IIB or III [residual tumor less than 1 cm] vs primary surgery: suboptimally debulked stage IV [residual tumor 1 cm or greater]).

Surgery

• Patients are assigned to one of two surgery groups:
• Group A: Patients undergo primary surgery comprised of hysterectomy, bilateral salpingo-oophorectomy (BSO), omentectomy, and resection of all tumor masses, if possible, before beginning chemotherapy. Patients with residual disease greater than 1 cm after completion of primary surgery receive 3 courses of chemotherapy, followed within 6 weeks by interval debulking surgery, followed within 3 weeks by the fourth course of chemotherapy.
• Group B: Patients undergo delayed surgery comprised of hysterectomy, BSO, omentectomy, and resection of all tumor masses, if possible, after completion of 3 courses of chemotherapy.

Chemotherapy

• Patients are randomized to 1 of 2 chemotherapy arms:
• Arm I: Patients receive epirubicin IV over 15-20 minutes, paclitaxel IV over 3 hours, and carboplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses. Patients with residual tumor after completion of 6 courses may receive 3 additional courses.
• Arm II: Patients receive paclitaxel and carboplatin as above but no epirubicin. Quality of life is assessed before beginning study, after completion of courses 3, 6, and 9 (if applicable), and then at 6 and 12 months after completion of study treatment.

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

PROJECTED ACCRUAL: A total of 800 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven stage IIB, III, or IV invasive ovarian epithelial, fallopian tube, or peritoneal cancer
• No symptomatic brain metastasis

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• WHO/ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal

Renal:

• Glomerular filtration rate at least 50 mL/min

Cardiovascular:

• No ventricular arrhythmia (LOWN class II or worse)
• No myocardial infarction within the past year
• No severe or uncontrolled hypertension
• No history of congestive heart disease (no New York Heart Association class III or IV heart disease) even if medically controlled
• LVEF at least 50%

Other:

• No other primary malignancies except carcinoma in situ of the cervix or basal cell skin cancer
• No worse than grade I preexisting motor or sensory neurologic pathology or symptoms
• No active infection or other serious underlying medical condition that would prevent compliance
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy
• No other concurrent antineoplastic agents

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• Not specified

Minnesota
      St. Mary's/Duluth Clinic Cancer Center, Duluth,  Minnesota,  55805,  United States
Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
Canada, Alberta
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada
Canada, Ontario
      Cancer Care Ontario-Hamilton Regional Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
Canada, Quebec
      Centre Hospitalier Universitaire de Quebec, Quebec City,  Quebec,  G1R 2J6,  Canada
      CHUS-Hopital Fleurimont, Fleurimont,  Quebec,  J1H 5N4,  Canada
Denmark
      Aalborg Hospital, Aalborg,  9100,  Denmark
      Odense University Hospital, Odense,  DK-5000,  Denmark
Israel
      Shaare Zedek Medical Center, Jerusalem,  91031,  Israel
Italy
      Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano (Milan),  20133,  Italy
      Ospedale di Circolo e Fondazione Macchi, Varese,  21100,  Italy
      Spedali Civili, Brescia,  25123,  Italy
Netherlands
      Medisch Spectrum Twente, ENSCHEDE,  7500 KA,  Netherlands
Norway
      Norwegian Radium Hospital, Oslo,  N-0310,  Norway
Portugal
      Hospitais da Universidade de Coimbra (HUC), Coimbra,  3049,  Portugal
      Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa, Lisbon,  1099-023 Codex,  Portugal
Spain
      Institut d'Oncologia Corachan, Barcelona,  08.017,  Spain

Study chairs or principal investigators

Gunnar B. Kristensen, MD, PhD,  Study Chair,  Norwegian Radium Hospital   
Ignace B. Vergote, MD, PhD,  Study Chair,  U.Z. Gasthuisberg   
Gavin C.E. Stuart, MD,  Study Chair,  Tom Baker Cancer Center - Calgary   

Study ID Numbers:  CDR0000067620; NSGO-OC9804; CAN-NCIC-OV14; EORTC-55981
Record last reviewed:  May 2003
Last Updated:  October 13, 2004
Record first received:  March 7, 2000
ClinicalTrials.gov Identifier:  NCT00004934
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08