Clinical trial NCT00004921: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ovarian Cancer
Keywords: stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Sozialmedizinisches Zentrum Ost - Donauspital
city: Charleroi
country: Belgium
facility: Centre Hospitalier Notre Dame - Reine Fabiola
city: Prague 10
country: Czech Republic
facility: Charles University
city: Prague 4
country: Czech Republic
facility: Thomayer Memorial Teaching Hospital
city: Karlsruhe
country: Germany
facility: Staedt Klinikum Karlsruhe GGMBH
city: Nuernberg
country: Germany
facility: Klinikum Nuernberg - Klinikum Nord
city: Bologna
country: Italy
facility: Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi
city: Pisa
country: Italy
facility: Ospedale Santa Chiara
city: Rome
country: Italy
facility: S. Camillo Hospital
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
city: Bratislava
country: Slovakia
facility: National Cancer Institute - Bratislava
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: London
country: United Kingdom
facility: Cancer Research UK and University College London Cancer Trials Centre
state: England
city: Manchester
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
Study officials:
affiliation: Cancer Research UK
name: Jonathan A. Ledermann, MD
role: STUDY_CHAIR
References:
citation: Mobus V, Wandt H, Frickhofen N, Bengala C, Champion K, Kimmig R, Ostermann H, Hinke A, Ledermann JA; AGO-Ovar/AIO; EBMT. Phase III trial of high-dose sequential chemotherapy with peripheral blood stem cell support compared with standard dose chemotherapy for first-line treatment of advanced ovarian cancer: intergroup trial of the AGO-Ovar/AIO and EBMT. J Clin Oncol. 2007 Sep 20;25(27):4187-93. doi: 10.1200/JCO.2006.09.7527. Epub 2007 Aug 13.