Clinical trial NCT00004934: Paclitaxel and Carboplatin With or Without Epirubicin in Treating Patients With Stage IIB, Stage III, or Stage IV Invasive Ovarian Epithelial, Fallopian Tube, or Peritoneal Cancer
Official title: A Randomized Trial of Paclitaxel/Epirubicin/Carboplatin Combination (TEC) Versus Paclitaxel/Carboplatin (TC) in the Treatment of Women With Advanced Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
Keywords: stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
fallopian tube cancer
primary peritoneal cavity cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: European Organisation for Research and Treatment of Cancer - EORTC
name: NCIC Clinical Trials Group
First posted: 2003-01-27
Sex: FEMALE
Minimum age (years): 18
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. 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Duluth
country: United States
facility: St. Mary's/Duluth Clinic Cancer Center
state: Minnesota
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Calgary
country: Canada
facility: Tom Baker Cancer Center - Calgary
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Hamilton
country: Canada
facility: Cancer Care Ontario-Hamilton Regional Cancer Centre
state: Ontario
city: Fleurimont
country: Canada
facility: CHUS-Hopital Fleurimont
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
city: Aalborg
country: Denmark
facility: Aalborg Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Brescia
country: Italy
facility: Spedali Civili
city: Milano (Milan)
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Oslo
country: Norway
facility: Norwegian Radium Hospital
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra (HUC)
city: Lisbon
country: Portugal
facility: Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa
city: Barcelona
country: Spain
facility: Institut d'Oncologia Corachan
Study officials:
affiliation: Norwegian Radium Hospital
name: Gunnar B. Kristensen, MD, PhD
role: STUDY_CHAIR
affiliation: University Hospital, Gasthuisberg
name: Ignace B. Vergote, MD, PhD
role: STUDY_CHAIR
affiliation: Tom Baker Cancer Centre - Calgary
name: Gavin C.E. Stuart, MD
role: STUDY_CHAIR
References:
citation: Kristensen GB, Vergote I, Stuart G, Del Campo JM, Kaern J, Lopez AB, Eisenhauer E, Aavall-Lundquist E, Ridderheim M, Havsteen H, Mirza MR, Scheistroen M, Vrdoljak E. First-line treatment of ovarian cancer FIGO stages IIb-IV with paclitaxel/epirubicin/carboplatin versus paclitaxel/carboplatin. Int J Gynecol Cancer. 2003 Nov-Dec;13 Suppl 2:172-7. doi: 10.1111/j.1525-1438.2003.13363.x.
citation: Kristensen G, Vergote I, Stuart G, et al.: First line treatment of ovarian cancer FIGO stages IIb-IV with paclitaxel/epirubicin/carboplatin (TEC) vs. paclitaxel/carboplatin (TC). Interim results of an NSGO-EORTC-NCIC CTG Gynecological Cancer Intergroup phase III trial. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-805, 2002.
citation: Lindemann K, Christensen RD, Vergote I, Stuart G, Izquierdo MA, Kaern J, Havsteen H, Eisenhauer E, Ridderheim M, Lopez AB, Hirte H, Aavall-Lundquvist E, Vrdoljak E, Green J, Kristensen GB. First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)--a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG. Ann Oncol. 2012 Oct;23(10):2613-2619. doi: 10.1093/annonc/mds060. Epub 2012 Apr 26.
citation: Kristensen GB, Vergote I, Stuart G, et al.: First-line treatment of ovarian/tubal/peritoneal cancer FIGO stage IIB-IV with paclitaxel/carboplatin with or without epirubicin (TEC vs TC). A gynecologic cancer intergroup study of the NSGO, EORTC GCG, and NCIC CTG. Results on progression-free survival. [Abstract] Int J Gynecol Cancer 15 (Suppl 3): 221, 2005.
citation: Kristensen GB, Vergote I, Eisenhauer E, et al.: First line treatment of ovarian/tubal/peritoneal cancer FIGO stage IIb-IV with paclitaxel/carboplatin with or without epirubicin (TEC vs TC). A Gynecologic Cancer Intergroup study of the NSGO, EORTC GCG, and NCIC CTG. Results on progression free survival. [Abstract] J Clin Oncol 22 (Suppl 14): A-5003, 449s, 2004.