High-Dose Chemotherapy Compared With Standard Chemotherapy in Treating Patients With Stage III or Stage IV Ovarian Epithelial Cancer That Has Been Removed During Surgery

Sponsor

EBMT Solid Tumors Working Party (Other)

Overall Status

Completed

CT.gov ID

NCT00004921

Collaborator

(none)

Locations

108

Duration (Months)

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Biological: filgrastim Drug: carboplatin Drug: cyclophosphamide Drug: melphalan Drug: paclitaxel Procedure: adjuvant therapy Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation	Phase 3

Detailed Description

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.

Arm I: 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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

A Randomized Phase III Trial of Sequential High Dose Chemotherapy or Standard Chemotherapy for Optimally Debulked FIGO Stage III and IV Ovarian Cancer

Study Start Date :

Sep 1, 1998

Actual Study Completion Date :

Sep 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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