Clinical trial NCT00052468: Carboplatin/Paclitaxel +/-Gemcitabine in Treating Patients With Ovarian Epithelial or Fallopian Tube Cancer
Official title: A Multi-National Randomized Phase-III GCIG Intergroup-Study Comparing 1st-line Chemotherapy With Gemcitabine/Paclitaxel/Carboplatin vs Paclitaxel/Carboplatin In Previously Untreated Patients With Epithelial Ovarian Cancer FIGO Stages I-IV
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Keywords: stage I ovarian epithelial cancer
stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
fallopian tube cancer
Lead sponsor: AGO Study Group
Sponsor class: OTHER
Collaborators: name: Nordic Society of Gynaecological Oncology - Clinical Trials Unit
name: GERCOR - Multidisciplinary Oncology Cooperative Group
First posted: 2003-01-27
Enrollment: 1742
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
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 whether carboplatin and paclitaxel combined with gemcitabine is more effective than carboplatin and paclitaxel alone in treating ovarian epithelial or fallopian tube cancer.

PURPOSE: This randomized phase III trial is studying carboplatin and paclitaxel combined with gemcitabine to see how well it works compared to paclitaxel and carboplatin alone in treating patients who have undergone surgery for ovarian epithelial or fallopian tube cancer.

Detailed description: OBJECTIVES:

* Compare overall survival in patients with stage I-IV ovarian epithelial or fallopian tube cancer treated with adjuvant carboplatin and paclitaxel with or without gemcitabine.
* Compare response rates, progression-free survival, and duration of response in patients treated with these regimens.
* Compare toxic effects of these regimens in these patients.
* Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, controlled, multicenter study. Patients are stratified according to FIGO stage (I-IIA vs IIB-IIIC and tumor no greater than 10 mm vs IIB-IIIC and tumor greater than 10 mm or IV), plan for interval surgical debulking (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive carboplatin IV over 30-60 minutes and paclitaxel IV over 3 hours on day 1 and gemcitabine IV over 30-60 minutes on days 1 and 8.
* Arm II: Patients receive carboplatin and paclitaxel as in arm I. Treatment in both arms repeats every 21 days for 6 to 10 courses in the absence of disease progression or unacceptable toxicity.

Some patients undergo interval debulking surgery.

Quality of life is assessed at baseline, after courses 3 and 6, and then at 3, 6, and 12 months after completion of study.

Patients are followed every 3 months for 2 years, every 6 months for up to 5 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,716 patients (858 per treatment arm) will be accrued for this study within 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed diagnosis of one of the following:

  * Ovarian epithelial cancer

    * FIGO stage IA/B G3, IC-IV
  * Fallopian tube cancer
  * Extra-ovarian papillary serous tumor
* The following are ineligible:

  * Low malignant-potential ovarian tumors (borderline tumors)
  * Non-epithelial ovarian tumors
  * Mixed Mullerian tumors
* Must have had definitive surgery within the past 6 weeks
* No symptomatic brain metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* At least 6 months

Hematopoietic

* WBC at least 3,000/mm\^3 OR
* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin greater than 10 mg/dL

Hepatic

* Bilirubin no greater than 2 times upper limit of normal

Renal

* Glomerular filtration rate at least 50 mL/min

Cardiovascular

* No congestive heart failure
* No myocardial infarction within the past 6 months
* No New York Heart Association class III or IV heart disease
* No prior atrial or ventricular arrhythmias

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No prior seizures or central nervous system disorder
* No prior severe hypersensitivity reaction to products containing Cremophor EL (e.g., cyclosporine or vitamin K)
* No known hypersensitivity to compounds chemically related to carboplatin, gemcitabine, or paclitaxel
* No preexisting motor or sensory neuropathy greater than grade 1
* No other malignancy within the past 5 years except:

  * Malignancies cured by surgery alone
  * Carcinoma in situ of the cervix
  * Adequately treated basal cell skin cancer
* No complete bowel obstruction
* No other concurrent severe medical condition that would preclude study participation
* No dementia or significantly altered mental status that would preclude study participation
* No concurrent severe active infection
* Geographically accessible for treatment and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent immunotherapy

Chemotherapy

* No prior chemotherapy
* No other concurrent chemotherapy

Endocrine therapy

* No concurrent hormonal therapy except:

  * Hormone replacement therapy
  * Antiemetic steroids

Radiotherapy

* No prior radiotherapy
* No concurrent radiotherapy

Surgery

* See Disease Characteristics
* Recovered from prior surgery

Other

* No other concurrent antineoplastic agents
* No other concurrent investigational drugs
* No other concurrent clinical trial enrollment

Primary outcomes:
measure: Overall Survival
timeFrame: Whole Study Period
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Whole Study Period
Other outcomes:
measure: Quality of Life
timeFrame: Whole Study Period
Locations:
city: Copenhagen
country: Denmark
facility: Herlev Hospital - University Hospital of Copenhagen
city: Paris
country: France
facility: Hotel Dieu de Paris
city: Bremen
country: Germany
facility: Zentralkrankenhaus
city: Dusseldorf
country: Germany
facility: Evangelisches Krankenhaus
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Frankfurt
country: Germany
facility: Staedtische Kliniken Frankfurt am Main - Hoechst
city: Hannover
country: Germany
facility: Frauenklinik der MHH
city: Karlsruhe
country: Germany
facility: Vincentius Krankenhaus
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein - Kiel Campus
city: Magdeburg
country: Germany
facility: Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
city: Muenster
country: Germany
facility: Klinik und Poliklinik fuer Frauenheilkunde und Geburtshilfe - Universitaetsklinikum Muenster
city: Munich
country: Germany
facility: Klinikum Grosshadern der Ludwig-Maximilians Universitaet Muenchen
city: Munich
country: Germany
facility: Klinikum Rechts Der Isar - Technische Universitaet Muenchen
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Ulm
country: Germany
facility: Universitaet Ulm
city: Wiesbaden
country: Germany
facility: Dr. Horst-Schmidt-Kliniken
city: Oslo
country: Norway
facility: Norwegian Radium Hospital
Study officials:
affiliation: Dr. Horst-Schmidt-Kliniken
name: Andreas du Bois, MD, PhD
role: STUDY_CHAIR
affiliation: Copenhagen County Herlev University Hospital
name: J. Herrstedt
role: STUDY_CHAIR
affiliation: Hotel Dieu de Paris
name: E. Pujade-Lauraine, MD, PhD
role: STUDY_CHAIR
References:
citation: du Bois A, Herrstedt J, Hardy-Bessard AC, Muller HH, Harter P, Kristensen G, Joly F, Huober J, Avall-Lundqvist E, Weber B, Kurzeder C, Jelic S, Pujade-Lauraine E, Burges A, Pfisterer J, Gropp M, Staehle A, Wimberger P, Jackisch C, Sehouli J. Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer. J Clin Oncol. 2010 Sep 20;28(27):4162-9. doi: 10.1200/JCO.2009.27.4696. Epub 2010 Aug 23.
citation: Machelon V, Gaudin F, Camilleri-Broet S, Nasreddine S, Bouchet-Delbos L, Pujade-Lauraine E, Alexandre J, Gladieff L, Arenzana-Seisdedos F, Emilie D, Prevot S, Broet P, Balabanian K. CXCL12 expression by healthy and malignant ovarian epithelial cells. BMC Cancer. 2011 Mar 16;11:97. doi: 10.1186/1471-2407-11-97.