First-line Irinotecan, Lederfolin and 5FU (FOLFIRI) and Bevacizumab in Patients With Advanced Colorectal Cancer
Condition: Colorectal Cancer Stage II
MeSH terms: Colorectal Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      Bevacizumab in combination with chemotherapy represents a standard of care for first-line
      treatment in patients with advanced colorectal cancer. Molecular predictive factors for
      bevacizumab efficacy have not yet been identified therefore selection of patients more likely
      to benefit from such a treatment approach is not possible. Retrospective analyses suggested
      that LDH serum levels may influence the clinical activity of anti-angiogenetic drugs. Primary
      aim of our clinical trial will be to prospectively ascertain whether bevacizumab in
      combination with chemotherapy has an improved clinical activity in patients with high LDH
      serum levels compared to patients with normal LDH serum levels
    

Detailed description: 
      The VEGF-driven tumour pathway has been demonstrated to represent a novel therapeutic target
      for an innovative class of antineoplastic agents. Among these antiangiogenetic-targeted
      treatment modalities the anti-VEGF monoclonal antibody bevacizumab has become a new standard
      of care for first-line treatment of metastatic colorectal cancer. The biological link between
      hypoxia, LDH levels and the tumour-driven angiogenesis pathway through the abnormal
      activation of the hypoxia Inducible factor 1 α (HIF1-α) is well established. HIF1-α is a key
      transcription factor that up-regulates a series of genes involved in glycolytic metabolism,
      angiogenesis, cell survival and erythropoiesis Accordingly to this biological assumption
      Azuma et al (Azuma et al 2007) demonstrated that high LDH serum levels were associated with
      tumour over-expression of VEGFA and VEGFR-1. As a clinical consequence it has been speculated
      that LDH levels may represent an indirect indicator of activated tumour angiogenesis and
      ultimately of worse prognosis We previously analysed the role of LDH pre-treatment serum
      levels in colorectal cancer patients receiving first-line bevacizumab in metastatic
      colorectal cancer treated with first-line bevacizumab were eligible. A control group
      including all consecutive patients treated with chemotherapy alone was also considered.
      Pre-treatment LDH serum levels were collected for all cases
    

Intervention name(s): Bevacizumab and FOLFIRI
Intervention type(s): Drug
Intervention description(s): The CENTRAL trial is a biologically enriched prospective phase II clinical trial in which patients treated with first-line modified FOLFIRI and bevacizumab will be prospectively stratified according to LDH serum levels.
After written informed consent patients will be enrolled. Patients will be considered evaluable for study aim if response rate was radiologically evaluated at least once during treatment course.
Treatment will be administered until progression, patients' withdrawal of consent, unacceptable toxicity
Other intervention name(s): CPT11; Folinic acid; 5FU
Intervention MeSH terms: Bevacizumab
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: colorectal cancer; advanced disease; LDH