A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme)

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Abstract

Background: Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. Methods/Design: OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80 % statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [18F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. Discussion: Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response. EudraCT Number: 2011-004997-27 Trial registration: ClinicalTrials.gove number, NCT01718873

Original languageEnglish
Article number69
JournalBMC Cancer
Volume16
Issue number1
DOIs
Publication statusPublished - Feb 8 2016

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Colorectal Neoplasms
Drug Therapy
Vascular Endothelial Growth Factor A
Therapeutics
Biomarkers
Second Primary Neoplasms
Bevacizumab
Diagnosis-Related Groups
Fluorodeoxyglucose F18
Rectal Neoplasms
Combination Drug Therapy
MicroRNAs
Positron-Emission Tomography
Sample Size
Disease-Free Survival
Single Nucleotide Polymorphism
Cause of Death
Appointments and Schedules
Radiotherapy
Monoclonal Antibodies

Keywords

  • Bevacizumab
  • Biomarkers for anti-angiogenic therapy
  • Colorectal cancer
  • FDG-PET
  • Oxaliplatin
  • Vessel normalization

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

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title = "A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme)",
abstract = "Background: Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. Methods/Design: OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80 {\%} statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [18F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. Discussion: Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response. EudraCT Number: 2011-004997-27 Trial registration: ClinicalTrials.gove number, NCT01718873",
keywords = "Bevacizumab, Biomarkers for anti-angiogenic therapy, Colorectal cancer, FDG-PET, Oxaliplatin, Vessel normalization",
author = "Antonio Avallone and Piccirillo, {Maria Carmela} and Luigi Aloj and Guglielmo Nasti and Paolo Delrio and Francesco Izzo and {Di Gennaro}, Elena and Fabiana Tatangelo and Vincenza Granata and Ernesta Cavalcanti and Piera Maiolino and Francesco Bianco and Pasquale Aprea and {De Bellis}, Mario and Biagio Pecori and Gerardo Rosati and Chiara Carlomagno and Alessandro Bertolini and Ciro Gallo and Carmela Romano and Alessandra Leone and Corradina Carac{\`o} and {de Lutio di Castelguidone}, Elisabetta and Gennaro Daniele and Orlando Catalano and Gerardo Botti and Antonella Petrillo and Romano, {Giovanni M.} and Iaffaioli, {Vincenzo R.} and Secondo Lastoria and Francesco Perrone and Alfredo Budillon",
year = "2016",
month = "2",
day = "8",
doi = "10.1186/s12885-016-2102-y",
language = "English",
volume = "16",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central Ltd.",
number = "1",

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TY - JOUR

T1 - A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme)

AU - Avallone, Antonio

AU - Piccirillo, Maria Carmela

AU - Aloj, Luigi

AU - Nasti, Guglielmo

AU - Delrio, Paolo

AU - Izzo, Francesco

AU - Di Gennaro, Elena

AU - Tatangelo, Fabiana

AU - Granata, Vincenza

AU - Cavalcanti, Ernesta

AU - Maiolino, Piera

AU - Bianco, Francesco

AU - Aprea, Pasquale

AU - De Bellis, Mario

AU - Pecori, Biagio

AU - Rosati, Gerardo

AU - Carlomagno, Chiara

AU - Bertolini, Alessandro

AU - Gallo, Ciro

AU - Romano, Carmela

AU - Leone, Alessandra

AU - Caracò, Corradina

AU - de Lutio di Castelguidone, Elisabetta

AU - Daniele, Gennaro

AU - Catalano, Orlando

AU - Botti, Gerardo

AU - Petrillo, Antonella

AU - Romano, Giovanni M.

AU - Iaffaioli, Vincenzo R.

AU - Lastoria, Secondo

AU - Perrone, Francesco

AU - Budillon, Alfredo

PY - 2016/2/8

Y1 - 2016/2/8

N2 - Background: Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. Methods/Design: OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80 % statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [18F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. Discussion: Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response. EudraCT Number: 2011-004997-27 Trial registration: ClinicalTrials.gove number, NCT01718873

AB - Background: Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. Methods/Design: OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80 % statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [18F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. Discussion: Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response. EudraCT Number: 2011-004997-27 Trial registration: ClinicalTrials.gove number, NCT01718873

KW - Bevacizumab

KW - Biomarkers for anti-angiogenic therapy

KW - Colorectal cancer

KW - FDG-PET

KW - Oxaliplatin

KW - Vessel normalization

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