Clinical trial NCT00039338: Chemotherapy Followed By Surgery Vs Radiotherapy Plus Chemotherapy in Patients With Stage IB or II Cervical Cancer
Official title: Randomized Phase III Study Of Neoadjuvant Chemotherapy Followed By Surgery Vs. Concomitant Radiotherapy And Chemotherapy In FIGO Ib2, IIa>4 cm or IIb Cervical Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Cervical Cancer
Keywords: stage IB cervical cancer
stage IIB cervical cancer
stage IIA cervical cancer
cervical squamous cell carcinoma
cervical adenocarcinoma
cervical adenosquamous cell carcinoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 686
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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. Giving chemotherapy drugs before surgery may shrink the tumor so that it can be removed during surgery. Radiation therapy uses high-energy x-rays to kill tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known whether chemotherapy is more effective followed by surgery or combined with radiation therapy in treating cervical cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy followed by radical hysterectomy with that of chemotherapy plus radiation therapy in treating patients who have stage IB or stage II cervical cancer.

Detailed description: OBJECTIVES:

* Compare the overall and progression-free survival of patients with stage IB2, IIA, or IIB cervical cancer treated with neoadjuvant cisplatin-based chemotherapy followed by radical hysterectomy vs standard therapy comprising concurrent radiotherapy and cisplatin-based chemotherapy.
* Compare the toxicity of these regimens in these patients.
* Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, FIGO stage, age (18 to 50 vs 51 to 75), and histological subtype (adenomatous vs non-adenomatous component). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive neoadjuvant cisplatin-based chemotherapy on day 1. Treatment repeats every 21 days. Within 6 weeks after the last chemotherapy course, patients undergo a type III-V Piver-Rutledge radical hysterectomy. Patients with positive lymph nodes or tumor invasion into the parametria or less than 5 mm from the resection borders after surgery receive standard adjuvant external beam radiotherapy once daily, 5 days a week, for 5-5.6 weeks (25-28 treatment days) followed by external boost radiotherapy or brachytherapy for 1 or 2 days.
* Arm II: Patients receive standard therapy comprising radiotherapy as in arm I concurrently with cisplatin-based chemotherapy once weekly for 6 weeks. Adjuvant hysterectomy is allowed, but not recommended, in case of histologically proven residual tumor.

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity. For patients in both arms, cisplatin may be combined with other chemotherapeutics as long as the minimum platinum dose is given.

Quality of life is assessed at baseline and at 6, 12, 18, and 24 months.

Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 686 patients (343 per treatment arm) will be accrued for this study within 3.8 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed cervical cancer, including the following subtypes:

  * Squamous cell carcinoma
  * Adenosquamous cell carcinoma
  * Adenocarcinoma (excluding small cell, clear cell, and other rare variants of the classical adenocarcinoma)
* FIGO stage IB2, IIA (greater than 4 cm), or IIB

PATIENT CHARACTERISTICS:

Age:

* 18 to 75

Performance status:

* WHO 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil count greater than 1,500/mm\^3
* Platelet count greater than 100,000/mm\^3

Hepatic:

* Bilirubin less than 1.46 mg/dL

Renal:

* Creatinine clearance greater than 60 mL/min

Other:

* No other prior or concurrent malignancy except adequately treated basal cell skin cancer
* No psychological, familial, sociological, or geographical condition that would preclude study
* Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy

Surgery:

* Not specified

Other:

* No other concurrent anticancer agent

Primary outcomes:
measure: Overall survival at 5 years
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Karl-Franzens-University Graz
city: Vienna
country: Austria
facility: Kaiser Franz Josef Hospital
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Liege
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Monza
country: Italy
facility: Ospedale San Gerardo
city: Naples
country: Italy
facility: Istituto Nazionale Per Lo Studio E La Cura Dei Tumori
city: Torino
country: Italy
facility: Ospedale Mauriziano Umberto I
city: Turin
country: Italy
facility: Clinica Universitaria
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
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: Erasmus MC - Daniel den Hoed Cancer Center
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum - Academisch Ziekenhuis
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra (HUC)
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Margate
country: United Kingdom
facility: Queen Elizabeth The Queen Mother Hospital
state: England
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre
state: Scotland
city: Maidstone, Kent
country: United Kingdom
facility: Mid Kent Oncology Centre
Study officials:
affiliation: Istituto Europeo Di Oncologia, Milano
name: Fabio Landoni, MD
role: STUDY_CHAIR
affiliation: Ospedale Alessandro Manzoni, Lecco
name: Alessandro Colombo, MD
role: STUDY_CHAIR
affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori, Napoli
name: Stefano Greggi, MD, PhD
role: STUDY_CHAIR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam
name: Gemma G. Kenter, MD
role: STUDY_CHAIR
References: