Bevacizumab-based Chemotherapy Adapted to Bevacizumab Pharmacokinetics in 1st-line Treatment
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-99
SponsorUniversity Hospital, Tours
About this trial
Bevacizumab is a standard drug for metastatic colorectal cancer (mCRC) in combination with cytotoxic chemotherapy. However, inter-individual pharmacokinetic variability was observed for bevacizumab and an exposure-response relationship for efficacy was described for bevacizumab in mCRC patients treated with 1st-line bevacizumab-based chemotherapy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients aged ≥18 years.
Histologically proven metastatic colorectal adenocarcinoma (on primary tumor and/or metastases) inoperable, well documented, i.e. not compatible with complete oncological resection at inclusion.
For whom treatment with bevacizumab is indicated.
For women of childbearing age: effective contraception.
Disqualifiers
Patient with a known non-indication or contraindication to first-line chemotherapy based on bevacizumab.
Cardiovascular contraindication to the prescription of bevacizumab: heart failure, cardiovascular event within 6 months, NYHA ≥ 2 (New York Heart Association), poorly controlled arterial hypertension, history of hypertensive crisis or hypertensive encephalopathy; Grade 3/4 anterior venous thromboembolism (NCI-CTCAE)
Inadequate hematological, hepatic and renal function
Urine test strip for proteinuria ≥ 2+ unless proteinuria < 1 g / 24 hours is demonstrated.
Trial design
Design model
Parallel
Treatments tested in this trial
Avastin, 25 Mg/mL Intravenous Solution
DrugExperimental group/ Patients randomized to the experimental group of the trial will receive bevacizumab as an IV infusion at a dose of 10 mg/kg, administered in 2 preparations of 5 mg/kg, every 2 weeks. Patients will receive treatment until progression, patient refusal, or unacceptable toxicity. Control group: Patients randomized to the control group of the trial will receive bevacizumab at a dose of 5 mg/kg and placebo (NaCl) every two weeks. Patients will receive treatment until progression, patient refusal, or unacceptable toxicity.
Treatment groups
244 Participants
are divided into 2 treatment groupsGroup A: Experimental: Group AExperimental treatment 1 intervention
Group B: Active comparator: Group BActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
The primary endpoint is progression-free survival (PFS)
The SS was defined as the time interval for randomized patients between the date of start of treatment and date of first clinical and/or radiological progression or death whatever the cause, in depending on what survives first.of first clinical and/or radiological progression or death whatever the cause, in depending on what survives first.progression (PD) per RECIST 1.1 or death due to any cause, whichever occurs first. A patient alive without progression will be censored on the date from the last follow-up visit.
Time frame
up to deathSecondary outcomes
1
Safety profile
Number of Participants Who Experienced an Adverse Event (AE) per NCI-CATCAE5.0 classification
Time frame
Up to approximately 10 months2
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date of last known contact.
Time frame
Up to approximately 25 months3
Best Overall Response Rate (BORR) Per RECIST1.1
BORR is defined as the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions). Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.
Time frame
Up to approximately 10 months4
Depth of response (DpR)
DpR was defined as the relative change in the sum of the target lesions' longest diameters at their smallest attained sizes compared to baseline time.
Time frame
Up to approximately 10 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
University Hospital, Tours
Lead sponsor
CHU DE BESANCON
Collaborator
Gustave Roussy, Cancer Campus, Grand Paris
Collaborator
University Hospital, Clermont-Ferrand
Collaborator
CHU de Reims
Collaborator
CHU de Brest
Collaborator
Pitié-Salpêtrière Hospital
Collaborator
University Hospital, Rouen
Collaborator
Poitiers University Hospital
Collaborator
Institut Paoli-Calmettes
Collaborator
Rennes University Hospital
Collaborator
University Hospital, Toulouse
Collaborator
AP-HP, Hôpital Saint-Louis
Collaborator
HCL Hôpital Edouard Hériot
Collaborator
Centre Hospitalier Universitaire Dijon
Collaborator
Nantes University Hospital
Collaborator
Centre Hospitalier Universitaire, Amiens
Collaborator
Hôpital Privé Jean Mermoz
Collaborator
AP-HP, Hôpital Henri Mondor
Collaborator
Hopital Paul Brousse
Collaborator
CHG de St-Malo
Collaborator
Polyclinique de Blois
Collaborator
University Hospital, Caen
Collaborator
Central Hospital, Nancy, France
Collaborator
Source ClinicalTrials.gov