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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01853813
Recruitment Status : Completed
First Posted : May 15, 2013
Last Update Posted : July 15, 2015
Sponsor:
Collaborator:
Azienda Ospedaliero, Universitaria Ospedali Riuniti
Information provided by (Responsible Party):
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

Brief 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

Condition or disease Intervention/treatment Phase
Colorectal Cancer Stage II Drug: Bevacizumab and FOLFIRI Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
Intervention Model: Single Group Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: First-line FOLFIRI and Bevacizumab in Patients With Advanced Colorectal Cancer Prospectively Stratified According to Serum LDH
Study Start Date : May 2013
Actual Primary Completion Date : May 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Bevacizumab and FOLFIRI
Bevacizumab 5 mg/kg d1 q14 in combination with FOLFIRI (Irinotecan, leucovorin, 5FU I.V.bolus and 5FU I.V. c.i.)
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

Other Names:
  • CPT11
  • Folinic acid
  • 5FU




Primary Outcome Measures :
  1. Response Rate [ Time Frame: RR will be evaluated every 12 weeks for 24 months ]
    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


Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: 18 months: time from the start of the treatment until PD or death ]
    Progression free survival to ascertain whether bevacizumab in combination with chemotherapy could determine an improved progression survival in patients with high serum LDH levels compared to patients with normal LDH serum levels

  2. evaluation of serum IL-8, bFGF, HGF, PlGF, SDF-1, MCP-3 [ Time Frame: every 12 weeks for 18 months ]
    Methods described by Kopetz et al (Kopetz, JCO 2010)


Other Outcome Measures:
  1. RECIST criteria and those defined by Chun [ Time Frame: every12 weeks for 18 months ]
    Radiological Criteria defined by Chun (Chun et al, JAMA 2009)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01853813


Locations
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Italy
A.O. Treviglio-Caravaggio, P.le Ospedale n1
Treviglio, Bergamo, Italy, 24047
Ospedale Civile
Carrara, Massa Carrara, Italy, 54033
A.O. Ospedale S.Paolo
Milano, MI, Italy, 20100
Istituto Oncologico Veneto
Padova, PD, Italy, 35124
Ospedale Santa Croce
Fano, PS, Italy, 61032
Azienda Ospedaliera San Carlo
Potenza, PZ, Italy, 85100
Università Policlinico Umberto I
Roma, RM, Italy, 00186
A.O. Universitaria - Ospedali Riuniti
Ancona, Italy, 60100
A.O. Ospedale G.Rummo
Benevento, Italy, 82100
Istituto Ospedaliero Fondazione Poliambulanza
Brescia, Italy, 25124
Ospedale Maggiore Policlinico
Milano, Italy, 20122
IRCCS Istituto Europeo di Oncologia
Milano, Italy, 20141
A.O. S.Giovanni Calabita Fatebenefratelli
Roma, Italy, 00186
Sponsors and Collaborators
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
Azienda Ospedaliero, Universitaria Ospedali Riuniti
Investigators
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Study Chair: Stefano Cascinu, PhD GISCAD Foundation

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Responsible Party: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
ClinicalTrials.gov Identifier: NCT01853813    
Other Study ID Numbers: 2012-005048-46
First Posted: May 15, 2013    Key Record Dates
Last Update Posted: July 15, 2015
Last Verified: July 2015
Keywords provided by Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente:
colorectal cancer
advanced disease
LDH
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Irinotecan
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action