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.

Condition	Treatment or Intervention	Phase
stage IB cervical cancer stage IIB cervical cancer stage IIA cervical cancer cervical squamous cell carcinoma cervical adenocarcinoma cervical adenosquamous cell carcinoma	Drug: cisplatin  Procedure: brachytherapy  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: neoadjuvant therapy  Procedure: radiation therapy  Procedure: surgery	Phase III

Further Study Details: 

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, after completion of the last chemotherapy course (arm I) or 4-8 weeks after completion of chemoradiotherapy (arm II), every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

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.

Ages Eligible for Study:  18 Years   -   75 Years,  Genders Eligible for Study:  Both

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

Argentina
      Hospital de Clinicas "Jose De San Martin", Buenos Aires,  1120,  Argentina; Recruiting
Austria
      Kaiser Franz Josef Hospital, Vienna,  A-1100,  Austria; Recruiting
      Karl-Franzens-University Graz, Graz,  A-8010,  Austria; Recruiting
Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
Italy
      Clinica Universita, Turin,  10126,  Italy; Recruiting
      European Institute of Oncology, Milano,  20141,  Italy; Recruiting
      Istituto Nazionale per lo Studio e la Cura dei Tumori, Naples,  80131,  Italy; Recruiting
      Ospedale di Circolo e Fondazione Macchi, Varese,  21100,  Italy; Recruiting
      Ospedale San Gerardo, Monza,  20052,  Italy; Recruiting
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands; Recruiting
      Daniel Den Hoed Cancer Center at Erasmus Medical Center, Rotterdam,  3008 AE,  Netherlands; Recruiting
      Leiden University Medical Center, Leiden,  2300 RC,  Netherlands; Recruiting
      Medisch Spectrum Twente, ENSCHEDE,  7500 KA,  Netherlands; Recruiting
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands; Recruiting
      University Medical Center Utrecht, Utrecht,  3584 CX,  Netherlands; Recruiting
      Vrije Universiteit Medisch Centrum, Amsterdam,  1007 MB,  Netherlands; Recruiting
Poland
      Medical University of Gdansk, Gdansk,  80-211,  Poland; Recruiting
Portugal
      Hospitais da Universidade de Coimbra (HUC), Coimbra,  3001-301,  Portugal; Recruiting
Spain
      Hospital Universitario San Carlos, Madrid,  28040,  Spain; Recruiting
United Kingdom, England
      Queen Elizabeth The Queen Mother Hospital, Margate,  England,  CT9 4AN,  United Kingdom; Recruiting
United Kingdom, Scotland
      Western Infirmary, Glasgow,  Scotland,  G11 6NT,  United Kingdom; Recruiting

Study chairs or principal investigators

Fabio Landoni, MD,  European Institute of Oncology   
Nicoletta Colombo, MD,  European Institute of Oncology   
Stefano Greggi, MD, PhD,  Istituto Nazionale per lo Studio e la Cura dei Tumori   
Gemma G. Kenter, MD,  Leiden University Medical Center   

Study ID Numbers:  CDR0000069375; EORTC-55994; NCT00039338
Record last reviewed:  January 2005
Last Updated:  April 4, 2005
Record first received:  June 6, 2002
ClinicalTrials.gov Identifier:  NCT00039338
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08