NCT01853813

First-line Irinotecan, Lederfolin and 5FU (FOLFIRI) and Bevacizumab in Patients With Advanced Colorectal Cancer

First-line FOLFIRI and Bevacizumab in Patients With Advanced Colorectal Cancer Prospectively Stratified According to Serum LDH

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 85 (actual)
• Sponsor: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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

Conditions

• Colorectal Cancer Stage II

Interventions

Type	Name	Description
DRUG	Bevacizumab and FOLFIRI	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

Timeline

• Start date: 2013-05-01
• Primary completion: 2015-05-01
• Completion: 2015-07-01
• First posted: 2013-05-15
• Last updated: 2015-07-15

Locations

13 sites across 1 country: Italy