Bevacizumab-based chemotherapy adaptive to pharmacokinetic of bevacizumab in first-line treatment of patients with unresectable metastatic colorectal cancer: A double-blind, multicenter, randomized phase III trial study (PHARBEVACOL trial)

Bevacizumab shows inter-individual pharmacokinetic variability, with an exposure-response relationship in metastatic colorectal cancer (mCRC) patients. This study explores whether a double dose of bevacizumab, compared to a standard dose, increases efficacy in mCRC patients treated with bevacizumab-based chemotherapy as first-line therapy and who have a low initial trough concentration of bevacizumab. PHARBEVACOL is a multicenter, randomized, double-blind, two-parallel group trial. All patients will receive first-line bi-weekly 5 mg/kg bevacizumab-based chemotherapy and those with low initial bevacizumab concentrations (≤15.5 mg/L) will be randomized to either continue the standard dose (5 mg/kg every 14 days) or receive a double dose (10 mg/kg every 14 days). The primary objective is to evaluate the effect of doubling dose on progression-free survival (PFS). During a screening phase, the first serum trough concentration will be measured on day 14, before the second infusion of bevacizumab. We hypothesize a 40 % PFS in the control group at 9 months versus 60 % in the study group, corresponding to a hazard ratio of 0.56. With 80 % power, a 5 % two-sided type I error, and a minimum 12-month follow-up, 116 patients need to be included. Since only 50 % of screened patients will be eligible for randomization, approximately 244 patients will be screened. Recruitment is scheduled to begin in February 2025.

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Publication Details

Journal
Digestive and Liver Disease
Published
2025-03-04
DOI
https://doi.org/10.1016/j.dld.2025.02.002
Citations
4
Primary Topic
Colorectal Cancer Treatments and Studies
Type
article
Field-Weighted Citation Impact
4.18
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article

Bevacizumab-based chemotherapy adaptive to pharmacokinetic of bevacizumab in first-line treatment of patients with unresectable metastatic colorectal cancer: A double-blind, multicenter, randomized phase III trial study (PHARBEVACOL trial)

Karine Bouhier‐Leporrier, Marie Müller, Marine Jary, Christophe Tournigand et al.
4 citations
Digestive and Liver Disease
Colorectal Cancer Treatments and Studies
4.18
article

Bevacizumab-based chemotherapy adaptive to pharmacokinetic of bevacizumab in first-line treatment of patients with unresectable metastatic colorectal cancer: A double-blind, multicenter, randomized phase III trial study (PHARBEVACOL trial)

Karine Bouhier‐Leporrier, Marie Müller, Marine Jary, Christophe Tournigand, Christophe Borg, Philippe Laplaige, Théodora Bejan‐Angoulvant, Fanny Foubert, Côme Lepage, David Ternant, Gilles Paintaud, David Tougeron, Thomas Aparicio, Vincent Hautefeuille, Fanny Monmousseau, Laurent Mineur, Pascal Artru, Olivier Bouché, Jean‐Philippe Metges, Thierry Lecomte, Michel Ducreux, Rémi Darrius, Bruno Giraudeau, Rosine Guimbaud, Jean-Marc Phelip, Romain Desgrippes, Sarah Lobet
article en
4 citations

Abstract

Bevacizumab shows inter-individual pharmacokinetic variability, with an exposure-response relationship in metastatic colorectal cancer (mCRC) patients. This study explores whether a double dose of bevacizumab, compared to a standard dose, increases efficacy in mCRC patients treated with bevacizumab-based chemotherapy as first-line therapy and who have a low initial trough concentration of bevacizumab. PHARBEVACOL is a multicenter, randomized, double-blind, two-parallel group trial. All patients will receive first-line bi-weekly 5 mg/kg bevacizumab-based chemotherapy and those with low initial bevacizumab concentrations (≤15.5 mg/L) will be randomized to either continue the standard dose (5 mg/kg every 14 days) or receive a double dose (10 mg/kg every 14 days). The primary objective is to evaluate the effect of doubling dose on progression-free survival (PFS). During a screening phase, the first serum trough concentration will be measured on day 14, before the second infusion of bevacizumab. We hypothesize a 40 % PFS in the control group at 9 months versus 60 % in the study group, corresponding to a hazard ratio of 0.56. With 80 % power, a 5 % two-sided type I error, and a minimum 12-month follow-up, 116 patients need to be included. Since only 50 % of screened patients will be eligible for randomization, approximately 244 patients will be screened. Recruitment is scheduled to begin in February 2025.

Digestive and Liver DiseaseVol. 57(5)
Université de Tours (FR), Inserm (FR), Université Paris-Est Créteil (FR), Institut Gustave Roussy (FR), Centre Hospitalier Universitaire de Nantes (FR), Centre Hospitalier Universitaire Henri-Mondor (FR), Centre Hospitalier Universitaire de Toulouse (FR), Centre Hospitalier Universitaire de Besançon (FR), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers (FR), Hopitaux Civils de Colmar (FR), Centre Hospitalier Universitaire de Tours (FR), Centre Hospitalier Universitaire Amiens-Picardie (FR), Assistance Publique – Hôpitaux de Paris (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), Clinical Investigation Center Plurithematic Tours (FR), Centre Hospitalier Universitaire de Reims (FR), Centre Hospitalier Universitaire de Poitiers (FR), Centre Hospitalier Universitaire de Caen Normandie (FR), Centre Hospitalier de Saint-Malo (FR), CHU Dijon Bourgogne (FR), Hôpital Privé Jean Mermo (FR), Thion Medical (France) (FR), Hôpitaux Universitaires Henri-Mondor (FR), Centre Hospitalier Régional Universitaire de Brest (FR), BP (France) (FR), Hôpital Saint-Louis (FR), Centre Hospitalier Universitaire de Saint-Étienne (FR), Institut Sainte Catherine (FR), Université de Reims Champagne-Ardenne (FR), Université de Caen Normandie (FR)
Good health and well-being
Openalex Percentile: Top 6%
Colorectal Cancer Treatments and Studies
4.18
DOIOpen Access PDFOpenAlex
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