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

NCT ID: NCT01853813

Last Updated: 2015-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2015-07-31

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

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.)

Group Type: OTHER

Bevacizumab and FOLFIRI

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

CPT11; Folinic acid; 5FU

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda Ospedaliero, Universitaria Ospedali Riuniti

OTHER

Sponsor Role: collaborator

Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefano Cascinu, PhD

Role: STUDY_CHAIR

GISCAD Foundation

Locations

A.O. Universitaria - Ospedali Riuniti

Ancona, Ancona, Italy

A.O. Ospedale G.Rummo

Benevento, Benevento, Italy

A.O. Treviglio-Caravaggio, P.le Ospedale n1

Treviglio, Bergamo, Italy

Istituto Ospedaliero Fondazione Poliambulanza

Brescia, Brescia, Italy

Ospedale Civile

Carrara, Massa Carrara, Italy

Ospedale Maggiore Policlinico

Milan, Milano, Italy

IRCCS Istituto Europeo di Oncologia

Milan, Milano, Italy

A.O. Ospedale S.Paolo

Milan, MI, Italy

Istituto Oncologico Veneto

Padua, PD, Italy

Ospedale Santa Croce

Fano, PS, Italy

Azienda Ospedaliera San Carlo

Potenza, PZ, Italy

Università Policlinico Umberto I

Roma, RM, Italy

A.O. S.Giovanni Calabita Fatebenefratelli

Roma, Roma, Italy

Countries

Italy

Other Identifiers

2012-005048-46

Identifier Type: -

Identifier Source: org_study_id