Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer

Ovarian Cancer Clinical Trial

Official title:

A Randomized Phase III Study Comparing Upfront Debulking Surgery Versus Neo-Adjuvant Chemotherapy in Patients With Stage IIIC or IV Epithelial Ovarian Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003636
• Other study ID #: EORTC-55971
• Secondary ID: EORTC-55971
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: August 4, 2015
• Start date: September 1998

Study information

• Verified date: August 2013
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining surgery with chemotherapy may kill more tumor cells. It is not yet known whether chemotherapy before surgery is more effective than chemotherapy after surgery in treating ovarian, peritoneal, or fallopian tube cancer.

PURPOSE: This randomized phase III trial is studying chemotherapy given before surgery to see how well it works compared to chemotherapy given after surgery with or without additional surgery in treating patients with stage III or stage IV ovarian cancer, peritoneal cancer, or fallopian tube cancer.

Description:

OBJECTIVES:

• Compare the overall survival and progression-free survival in patients with stage IIIC or IV ovarian epithelial, peritoneal, or fallopian tube carcinoma treated with neoadjuvant chemotherapy followed by interval debulking surgery versus upfront cytoreductive surgery followed by chemotherapy with or without interval debulking surgery.

• Compare the quality of life of patients treated with these regimens.

• Compare the different treatment complications in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, method of biopsy, stage, largest tumor size before surgery, and intent to also randomize on EORTC-55012. Patients are randomized to one of two treatment arms.

• Arm I: Patients undergo upfront maximal cytoreductive surgery followed by cisplatin or carboplatin IV every 3 weeks for 3 courses. Patients with non-optimal primary debulking may undergo interval debulking surgery at the physician's discretion. All patients then receive an additional 3 courses of the same regimen of chemotherapy.

• Arm II: Patients receive chemotherapy as in arm I. Patients with stable or responding disease undergo interval debulking surgery followed by an additional 3 courses of the same regimen of chemotherapy.

Second-look surgery is allowed for both arms if clinically indicated.

Quality of life (QOL) is assessed prior to treatment, after the third and sixth course of chemotherapy, and at 6 and 12 months after study. Patients who are also randomized on EORTC-55012 follow the QOL assessment schedule for EORTC-55012 only.

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

PROJECTED ACCRUAL: A total of 704 patients will be accrued for this study within 4 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 704
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically proven stage IIIC or IV ovarian epithelial carcinoma, peritoneal carcinoma, or fallopian tube carcinoma

• If biopsy is not available, evidence of adenocarcinoma by fine needle aspiration allowed if all of the following are true:

• Presence of pelvic ovarian mass

• Omental cake or other metastasis larger than 2 cm in the upper abdomen and/or regional lymph node metastasis

• CA 125/carcinoembryonic antigen ratio greater than 25 (if ratio less than 25, barium enema or colonoscopy AND gastroscopy or radiological examination of the stomach must be negative for primary tumor)

• Normal mammography (if CA 125/carcinoembryonic antigen ratio less than 25)

• Tumor greater than 2 cm, excluding ovaries, on laparoscopy or CT scan

• No brain or leptomeningeal metastases

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 3,000/mm^3

• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 1.25 times upper limit of normal (ULN)

Renal:

• Creatinine less than 1.25 times ULN

Other:

• No other serious disabling diseases contraindicating primary cytoreductive surgery or primary platin-based chemotherapy

• No other prior primary malignancies except carcinoma in situ of the cervix or basal cell carcinoma of the skin

• No psychological, familial, sociological, or geographical condition potentially preventing protocol compliance or follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• No other prior procedures except diagnostic biopsy by laparotomy or laparoscopy

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Peritoneal Neoplasms
• Primary Peritoneal Cavity Cancer

Intervention

Drug:
• carboplatin

• cisplatin

Procedure:
• conventional surgery

• neoadjuvant therapy

Locations

Country	Name	City	State
Argentina	Hospital de Clinicas "Jose De San Martin"	Buenos Aires
Argentina	Shaare Zedek Medical Center	Buenos Aires
Austria	Karl-Franzens-University Graz	Graz
Austria	Innsbruck Universitaetsklinik	Innsbruck
Austria	Allgemeines Krankenhaus - Universitatskliniken	Vienna
Austria	Ludwig Boltzmann Institute for Applied Cancer Research at Kaiser Franz Josef Hospital	Vienna
Belgium	Academisch Ziekenhuis der Vrije Universiteit Brussel	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Cazk Groeninghe - Campus Maria's Voorzienigheid	Kortrijk
Belgium	U.Z. Gasthuisberg	Leuven
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	CHUS-Hopital Fleurimont	Fleurimont	Quebec
Canada	Hopital Charles Lemoyne	Greenfield Park	Quebec
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	Hopital Notre-Dame du CHUM	Montreal	Quebec
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Doctor H. Bliss Murphy Cancer Centre	St. Johns	Newfoundland and Labrador
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	British Columbia Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Denmark	Herlev Hospital - University Hospital of Copenhagen	Copenhagen
France	Institut Bergonie	Bordeaux
France	Centre Hospitalier Regional et Universitaire de Lille	Lille
France	Centre Oscar Lambret	Lille
France	Institut Claudius Regaud	Toulouse
Germany	Martin Luther Universitaet	Halle
Ireland	Coombe Women's Hospital	Dublin
Ireland	St. James's Hospital	Dublin
Italy	Spedali Civili di Brescia	Brescia
Italy	Mirano General Hospital	Mirano-Venice
Italy	Libero Istituto Universitario Campus Bio-Medico	Rome
Italy	Azienda Sanitaria Ospedaliera Ordine Mauriziano	Torino
Italy	Clinica Universitaria	Turin
Netherlands	Academisch Medisch Centrum at University of Amsterdam	Amsterdam
Netherlands	Akademisch Ziekenhuis Vrije Universiteit - Medisch Centrum	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen
Netherlands	Daniel Den Hoed Cancer Center at Erasmus Medical Center	Rotterdam
Netherlands	Erasmus MC - Sophia Children's Hospital	Rotterdam
Norway	Haukeland Hospital - University of Bergen	Bergen
Norway	Norwegian Radium Hospital	Oslo
Portugal	Hospitais da Universidade de Coimbra (HUC)	Coimbra
Portugal	Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A.	Lisbon
Spain	Institut d'Oncologia Corachan	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario San Carlos	Madrid
Spain	Hospital Universitario Central de Asturias	Oviedo
Sweden	Lund University Hospital	Lund
Sweden	Karolinska University Hospital - Huddinge	Stockholm
Sweden	Umea Universitet	Umea
Sweden	Uppsala University Hospital	Uppsala
United Kingdom	Royal United Hospital	Bath	England
United Kingdom	Cheltenham General Hospital	Cheltenham	England
United Kingdom	Western Infirmary	Glasgow	Scotland
United Kingdom	University College of London Hospitals	London	England
United Kingdom	Queen Elizabeth The Queen Mother Hospital	Margate
United Kingdom	Clatterbridge Centre for Oncology NHS Trust	Merseyside	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Nottingham City Hospital NHS Trust	Nottingham	England
United Kingdom	Staffordshire General Hospital	Stafford	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Argentina,  Austria,  Belgium,  Canada,  Denmark,  France,  Germany,  Ireland,  Italy,  Netherlands,  Norway,  Portugal,  Spain,  Sweden,  United Kingdom, 

References & Publications (4)

Chi DS, Musa F, Dao F, Zivanovic O, Sonoda Y, Leitao MM, Levine DA, Gardner GJ, Abu-Rustum NR, Barakat RR. An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT). Gynecol Oncol. 2012 Jan;124(1):10-4. doi: 10.1016/j.ygyno.2011.08.014. Epub 2011 Sep 13. — View Citation

Fruehauf JP, Yu I, Parker R: In vitro drug response and biomarker profiles for ovarian cancer specimens obtained at initial debulking or after neoadjuvant chemotherapy (EORTC 55971). [Abstract] Proceedings of the American Society of Clinical Oncology 21:

Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS; European Organization for Research and Treatment of — View Citation

Verleye L, Ottevanger PB, Kristensen GB, Ehlen T, Johnson N, van der Burg ME, Reed NS, Verheijen RH, Gaarenstroom KN, Mosgaard B, Seoane JM, van der Velden J, Lotocki R, van der Graaf W, Penninckx B, Coens C, Stuart G, Vergote I. Quality of pathology repo — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival as measured by Kaplan Meier every 3 months for 2 years, every 6 months for 3 years, and then annually			No
Secondary	Progression-free survival as measured by Kaplan Meier and RECIST every 3 months for 2 years, every 6 months for 3 years, and then annually			No
Secondary	Health-related quality of life as measured by Quality of Life Questionnaire-C30 after courses 1, 3 and 6, then at 6 and 12 months			No
Secondary	Toxicity as measured by NCIC Common Toxicity Criteria v2.0 within 4 weeks of surgery			Yes