Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage IB, Stage II, or Stage IIIB Cervical Cancer

OBJECTIVES:

Primary

• Evaluate the efficacy of treatment with cetuximab and a standard radiochemotherapy regimen (pelvic radiotherapy and cisplatin) in patients with stage IB2, II, and IIIB cervical cancer by evaluating the number of patients without recurrence at 2 years.

Secondary

• Analyze the tumor response by MRI after external radiotherapy.
• Assess the tolerance of cetuximab and standard radiochemotherapy in patients not previously treated and in generally good condition.
• Study the correlation between treatment response and analysis of EGFR mutations (exons 18-21 of the tyrosine kinase domain including the two hot spots L858R and E746-A750).
• Study the correlation between treatment response and evaluation of number of copies of the EGFR gene.
• Study the correlation between treatment response and analysis of mutations of codons 12 and 13 of KRAS2 by direct sequencing.
• Study the correlation between treatment response and research of DNA sequences of human papillomavirus.
• Study the correlation between treatment response and overexpression of EGFR and COX2 (centralized) by IHC.
• Study the correlation between treatment response and characterization of a genomic signature (genome, transcriptome, and Affymetrix chips from samples frozen in liquid nitrogen).
• Collect tumor samples for molecular analysis.

OUTLINE: This is a multicenter study. Patients are stratified according to planned surgery (yes vs no) and are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cisplatin IV over 1 hour once weekly during weeks 1-6. Patients also undergo pelvic radiotherapy 5 days a week during weeks 2-5 or 2-6.
• Arm II: Patients receive cisplatin and undergo radiotherapy as in arm I. Patients also receive cetuximab IV over 1 hour once weekly during weeks 1-6.

After 6-8 weeks of study treatment, patients continue treatment as recommended by their center (i.e., utero-vaginal brachytherapy, additional radiotherapy, or surgery).

Tumor tissue and blood samples are collected for further analysis.

After completion of study treatment, patients are followed at 3-4 weeks and then every 4 months for 2 years.

DISEASE CHARACTERISTICS:

• Diagnosis of cervical cancer

• Squamous cell carcinoma or adenocarcinoma
• Stage IB2-IIIB disease
• Not immediately operable
• Origin of the tumor and presence of measurable target lesion according to RECIST criteria confirmed by T2-weighted MRI
• Data imaging scan and PET scan (optional) confirmed absence of lumbo-aortic adenopathy
• No other associated pathology that would preclude study treatment

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Hemoglobin > 10 g/dL
• ANC > 1,500/mm^3
• Platelet count > 100,000/mm^3
• Alkaline phosphatase < 2 times normal
• Total bilirubin < 1.5 times normal
• Creatinine < 130 μmol/L
• Creatinine clearance ≥ 60 mL/min
• Normal vital functions
• Not pregnant
• Fertile patients must use effective contraception
• Able to provide the imaging exams on CD ROM (DICOM 3.0 or higher) for centralized review
• No history of another cancer that recurred within the past 5 years except for basal cell carcinoma of the skin or carcinoma in situ of the cervix
• No absolute contraindication to MRI (i.e., claustrophobia, pacemaker, or cochlear implant)
• No geographical, social, or psychological situations that preclude study follow up
• Not deprived of liberty or under guardianship
• Receiving benefits from a social security system

PRIOR CONCURRENT THERAPY:

• No prior treatment (i.e., chemotherapy, radiotherapy, immunotherapy, hormonal therapy, or, especially, therapy with an investigational agent) for this cancer
• No concurrent participation in a clinical trial with an experimental agent