Clinical trial NCT00003636: Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
Keywords: stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
fallopian tube cancer
primary peritoneal cavity cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 704
Sex: FEMALE
Standard ages: CHILD
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 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival as measured by Kaplan Meier every 3 months for 2 years, every 6 months for 3 years, and then annually
Secondary outcomes:
measure: 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
measure: 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
measure: Toxicity as measured by NCIC Common Toxicity Criteria v2.0 within 4 weeks of surgery
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital de Clinicas "Jose De San Martin"
city: Buenos Aires
country: Argentina
facility: Shaare Zedek Medical Center
city: Graz
country: Austria
facility: Karl-Franzens-University Graz
city: Innsbruck
country: Austria
facility: Innsbruck Universitaetsklinik
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus - Universitatskliniken
city: Vienna
country: Austria
facility: Ludwig Boltzmann Institute for Applied Cancer Research at Kaiser Franz Josef Hospital
city: Brussels
country: Belgium
facility: Academisch Ziekenhuis der Vrije Universiteit Brussel
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Kortrijk
country: Belgium
facility: Cazk Groeninghe - Campus Maria's Voorzienigheid
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre - Calgary
state: Alberta
city: Surrey
country: Canada
facility: BCCA - Fraser Valley Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: St. Johns
country: Canada
facility: Doctor H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: Fleurimont
country: Canada
facility: CHUS-Hopital Fleurimont
state: Quebec
city: Greenfield Park
country: Canada
facility: Hopital Charles Lemoyne
state: Quebec
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
city: Montreal
country: Canada
facility: Hopital Notre-Dame du CHUM
state: Quebec
city: Copenhagen
country: Denmark
facility: Herlev Hospital - University Hospital of Copenhagen
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: Centre Hospitalier Regional et Universitaire de Lille
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Halle
country: Germany
facility: Martin Luther Universitaet
city: Dublin
country: Ireland
facility: Coombe Women's Hospital
city: Dublin
country: Ireland
facility: St. James's Hospital
city: Brescia
country: Italy
facility: Spedali Civili di Brescia
city: Mirano-Venice
country: Italy
facility: Mirano General Hospital
city: Rome
country: Italy
facility: Libero Istituto Universitario Campus Bio-Medico
city: Torino
country: Italy
facility: Azienda Sanitaria Ospedaliera Ordine Mauriziano
city: Turin
country: Italy
facility: Clinica Universitaria
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Akademisch Ziekenhuis Vrije Universiteit - Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Rotterdam
country: Netherlands
facility: Daniel Den Hoed Cancer Center at Erasmus Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Sophia Children's Hospital
city: Bergen
country: Norway
facility: Haukeland Hospital - University of Bergen
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 Regional de Oncologia de Lisboa, S.A.
city: Barcelona
country: Spain
facility: Institut d'Oncologia Corachan
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Lund
country: Sweden
facility: Lund University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital - Huddinge
city: Umea
country: Sweden
facility: Umea Universitet
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Bath
country: United Kingdom
facility: Royal United Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
state: England
city: London
country: United Kingdom
facility: University College of London Hospitals
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Trust
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Stafford
country: United Kingdom
facility: Staffordshire General Hospital
state: England
city: Glasgow
country: United Kingdom
facility: Western Infirmary
state: Scotland
city: Margate
country: United Kingdom
facility: Queen Elizabeth The Queen Mother Hospital
Study officials:
affiliation: U.Z. Gasthuisberg, Leuven
name: Ignace B. Vergote, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
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 reports for advanced ovarian cancer: are we missing essential information? An audit of 479 pathology reports from the EORTC-GCG 55971/NCIC-CTG OV13 neoadjuvant trial. Eur J Cancer. 2011 Jan;47(1):57-64. doi: 10.1016/j.ejca.2010.08.008. Epub 2010 Sep 16.
citation: Vergote I, Trope 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 Cancer-Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010 Sep 2;363(10):943-53. doi: 10.1056/NEJMoa0908806.
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: A-2177, 2002.
citation: Tajik P, van de Vrie R, Zafarmand MH, Coens C, Buist MR, Vergote I, Bossuyt PMM, Kenter GG. The FIGO Stage IVA Versus IVB of Ovarian Cancer: Prognostic Value and Predictive Value for Neoadjuvant Chemotherapy. Int J Gynecol Cancer. 2018 Mar;28(3):453-458. doi: 10.1097/IGC.0000000000001186.
citation: Vizzielli G, Fanfani F, Chiantera V, Tortorella L, Lucidi A, Petrillo M, Costantini B, Scambia G, Fagotti A. Does the diagnosis center influence the prognosis of ovarian cancer patients submitted to neoadjuvant chemotherapy? Anticancer Res. 2015 May;35(5):3027-32.
citation: van Meurs HS, Tajik P, Hof MH, Vergote I, Kenter GG, Mol BW, Buist MR, Bossuyt PM. Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial. Eur J Cancer. 2013 Oct;49(15):3191-201. doi: 10.1016/j.ejca.2013.06.013. Epub 2013 Jul 11.