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

Phase 2
18 Years
75 Years
Not Enrolling
Colorectal Cancer Stage II

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Trial Information

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

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

Inclusion Criteria:

- Written informed consent

- No prior treatment for advanced disease (adjuvant therapy allowed)

- age < 75 years < 18 years

- Histologically/cytologically confirmed advanced, colorectal cancer

- At least one lesion measurable with CT or MRI scan

- Performance Status (ECOG) 0-1 at study entry)

- Life expectancy of at least 6 months

- Neutrophils count =/> 1.5 x 109/L, platelets count =/> 100 x 109/L, HGB =/> 10 g/dL

- total bilirubin < 1.5 x UNL • SGOT and SGPT =/< 2.5 x UNL (=/< 5 x UNL in patients
with liver metastases)

- Creatinine < 1.5 x UNL

Exclusion Criteria:

- CNS metastases

- Severe cardiovascular disease

- Uncontrolled infections

- Radiotherapy within 4 weeks of study entry

- Any experimental drug administered within 4 weeks of study entry

- Known hypersensitivity to study drug

- Known drugs or alcohol abuse

- Pregnant or lactating women (serum Betahcg test)

- Other tumours, except in situ melanoma or cervix cancer if radically removed

- Incapability to sign informed consent

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Outcome Measure:

Response Rate

Outcome Description:

Response rate to ascertain whether bevacizumab in combination with chemotherapy could determine an improved response rate in patients with high LDH serum levels compared to patients with normal LDH serum levels

Outcome Time Frame:

RR will be evaluated every 12 weeks for 24 months

Safety Issue:


Principal Investigator

Stefano Cascinu, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

GISCAD Foundation


Italy: The Italian Medicines Agency

Study ID:




Start Date:

May 2013

Completion Date:

December 2015

Related Keywords:

  • Colorectal Cancer Stage II
  • colorectal cancer
  • advanced disease
  • LDH
  • Colorectal Neoplasms