Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage IB, Stage II, or Stage IIIB Cervical Cancer
Condition: Cervical Cancer
MeSH terms: Uterine Cervical Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in
      chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells,
      either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as
      cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to
      grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances
      to them. It is not yet known whether radiation therapy given together with cisplatin is more
      effective with or without cetuximab in treating patients with cervical cancer.

      PURPOSE: This randomized phase II trial is studying giving radiation therapy together with
      cisplatin to see how well it works compared with radiation therapy and cisplatin given
      together with cetuximab in treating patients with stage IB, stage II, or stage IIIB cervical
      cancer.
    

Detailed description: 
      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.
    

Intervention name(s): cetuximab; cisplatin
Intervention type(s): Biological; Drug
Intervention description(s): Given IV; Given IV
Intervention MeSH terms: Cetuximab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IB cervical cancer; stage IIA cervical cancer; stage IIB cervical cancer; stage III cervical cancer; cervical adenocarcinoma; cervical squamous cell carcinoma