Clinical trial NCT00006454: Paclitaxel Plus Carboplatin With or Without Topotecan in Treating Patients With Stage IIB, Stage III, or Stage IV Ovarian Epithelial Cancer
Official title: Phase III Multicenter Study in Epithelial Ovarian Carcinoma FIGO Stage IIB-IV Comparing Treatment With Paclitaxel and Carboplatin to Paclitaxel and Carboplatin Sequentially Followed by Topotecan
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Keywords: 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
First posted: 2004-02-03
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
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 if paclitaxel plus carboplatin is more effective with or without topotecan for ovarian epithelial cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of paclitaxel plus carboplatin with or without topotecan in treating patients who have stage IIB, stage III, or stage IV ovarian epithelial cancer.

Detailed description: OBJECTIVES: I. Compare survival of patients with stage IIB, III, or IV ovarian epithelial carcinoma after receiving treatment with paclitaxel and carboplatin with or without topotecan. II. Compare progression-free survival of these patients after receiving these treatment regimens. III. Compare the response rate and response duration in these patients treated with these regimens. IV. Determine the toxic effects of the combination of paclitaxel, carboplatin, and topotecan in these patients. V. Compare the toxic effects of these treatment regimens in these patients. VI. Compare quality of life of these patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and stage (stage IIB and stage III optimally debulked to no greater than 1 cm residual tumor vs stage IV regardless of residual tumor or residual tumor greater than 1 cm). Patients are randomized to one of two treatment arms. Arm I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 0.5-1 hour on day 1 and topotecan IV over 0.5 hour on days 1-5. Treatment repeats every 21 days for 6 courses (topotecan is administered for 4 courses only). Arm II: Patients receive paclitaxel and carboplatin as in arm I. Treatment repeats every 21 days for 6 courses. Quality of life is assessed before courses 1, 3, and 5 and at 3 weeks and 3 months after completion of treatment in both treatment arms; before courses 1 and 3 of topotecan in arm I; and at 6 months after completion of treatment in arm II. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 914 patients (457 per treatment arm) will be accrued for this study over 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically confirmed stage IIB, III, or IV ovarian epithelial carcinoma, fallopian tube, or extraovarian papillary serous carcinoma extending to the ovary No mixed epithelial/non-epithelial tumors (e.g., mixed Mullerian tumors) No tumors of low malignant potential (e.g., borderline tumors) No symptomatic brain metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 OR Karnofsky 70-100% Life expectancy: More than 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times the upper limit of normal (ULN) Alkaline phosphatase no greater than 3 times ULN Renal: Creatinine no greater than 1.25 times ULN Estimated glomerular filtration rate at least 60 mL/min Cardiovascular: No history of congestive heart failure (even if medically controlled) No New York Heart Association class III or IV heart disease No myocardial infarction within the past 6 months No history of atrial or ventricular arrhythmias Other: No motor or sensory neurologic pathology or symptoms greater than grade 1 No active infection or other serious medical condition that would preclude study No prior allergy to drug containing Cremophor EL No dementia or significantly altered mental state that would preclude informed consent No complete bowel obstruction No other prior malignancy except curatively treated nonmelanomatous skin cancer or carcinoma in situ of the cervix Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy No concurrent WBC transfusions Chemotherapy: No prior chemotherapy No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy Radiotherapy: No prior radiotherapy No concurrent radiotherapy Surgery: No more than 6 weeks since prior definitive laparotomy and recovered Other: No other concurrent antineoplastic agents No other concurrent investigational drugs

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Universitaetsklinikum Charite
city: Bonn
country: Germany
facility: Universitaetskliniken Bonn
city: Bremen
country: Germany
facility: Zentralkrankenhaus
city: Dresden
country: Germany
facility: Medizinische Klinik I
city: Duesseldorf
country: Germany
facility: Universitaetsklinik Duesseldorf
city: Dusseldorf
country: Germany
facility: Evangelisches Krankenhaus
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Goethe Universitaet
city: Frankfurt
country: Germany
facility: Stadtische Kliniken Frankfurt-Hochst
city: Gottingen
country: Germany
facility: Universitaetsklinik Goettingen
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Hannover
country: Germany
facility: Frauenklinik der MHH
city: Karlsruhe
country: Germany
facility: Vincentius Krankenhaus
city: Kiel
country: Germany
facility: Christian-Albrechts University of Kiel
city: Magdeburg
country: Germany
facility: Klinik der Otto-v.-Guericke-Universitat
city: Muenster
country: Germany
facility: Klinik und Poliklinik fuer Kinderheilkunde
city: Munich
country: Germany
facility: Klinikum Grosshadern
city: Munich
country: Germany
facility: Klinikum Rechts Der Isar/Technische Universitaet Muenchen
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Wiesbaden
country: Germany
facility: Dr. Horst-Schmidt-Kliniken
Study officials:
affiliation: University Hospital Schleswig-Holstein
name: Jacobus Pfisterer, MD
role: STUDY_CHAIR
References:
citation: Greimel ER, Bjelic-Radisic V, Pfisterer J, Hilpert F, Daghofer F, Pujade-Lauraine E, du Bois A; Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR); Groupe d'Investigateurs Nationaux pour les Etudes des Cancers de l'Ovaire (GINECO). Toxicity and quality of life outcomes in ovarian cancer patients participating in randomized controlled trials. Support Care Cancer. 2011 Sep;19(9):1421-7. doi: 10.1007/s00520-010-0969-8. Epub 2010 Aug 6.
citation: Pfisterer J, Weber B, Reuss A, Kimmig R, du Bois A, Wagner U, Bourgeois H, Meier W, Costa S, Blohmer JU, Lortholary A, Olbricht S, Stahle A, Jackisch C, Hardy-Bessard AC, Mobus V, Quaas J, Richter B, Schroder W, Geay JF, Luck HJ, Kuhn W, Meden H, Nitz U, Pujade-Lauraine E; AGO-OVAR; GINECO. Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO. J Natl Cancer Inst. 2006 Aug 2;98(15):1036-45. doi: 10.1093/jnci/djj296.
citation: Pfisterer J, Lortholary A, Kimmig R, et al.: Paclitaxel/carboplatin (TC) vs. paclitaxel/carboplatin followed by topotecan (TC-Top) in first-line treatment of ovarian cancer FIGO stages IIb - IV. Interim results of a gynecologic cancer intergroup phase III trial of the AGO Ovarian Cancer Study Group and GINECO. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1793, 446, 2003.