Trial Title:
Bevacizumab-based Chemotherapy Adapted to Bevacizumab Pharmacokinetics in 1st-line Treatment
NCT ID:
NCT06642844
Condition:
Unresectable Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Bevacizumab
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
This project is a multicenter, double-blind, randomized trial in two parallel groups.
Primary purpose:
Treatment
Masking:
Double (Participant, Investigator)
Masking description:
Double blinding (patients and investigators) will be applied to this trial with respect
to the dose of bevacizumab administered throughout the study, except in specific
circumstances such as in emergency cases, and only if knowledge of the dose is likely to
influence management.
The dose of bevacizumab will be administered in 2 preparations and in the following
order:
-
1. Preparation at 5 mg/kg, open label;
-
2. Preparation at 5 mg/kg or placebo, blinded.
Intervention:
Intervention type:
Drug
Intervention name:
Avastin, 25 Mg/mL Intravenous Solution
Description:
Experimental 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.
Arm group label:
Active comparator: Group B
Arm group label:
Experimental: Group A
Other name:
Experimental group
Other name:
Control group
Summary:
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.
Detailed description:
The primary objective is to evaluate the effect of doubling the dose of bevacizumab in
mCRC patients whose initial serum bevacizumab concentration is ≤15.5 mg/L on
progression-free survival (PFS).
This project is a multicenter, double-blind, randomized trial in two parallel groups.
The primary endpoint is progression-free survival (PFS)
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
- ECOG Performance status (PS) 0-2.
- No prior treatment of metastatic disease (in the case of adjuvant treatment,
interval between the end of chemotherapy and relapse > 6 months if fluoropyrimidine
alone or > 12 months if FOLFOX).
- At least one evaluable or measurable lesion assessed by computed tomography (CT)
according to RECIST v1.1 criteria.
- Life expectancy greater than 3 months.
- Adequate hematological, renal and hepatic biological parameters: neutrophils ≥
1.5x109/L; platelets ≥ 100x109/L; hemoglobin ≥ 9 g/dL; serum creatinine <150 μmol/L;
bilirubinemia ≤ 1.5 x upper limit of normal (ULN), alkaline phosphatase < 5xULN;
proteinuria < 2+ (urine dipstick) or ≤ 1 g/24h.
- Written informed consent signed by the patient.
- Patient affiliated to a French social security system.
Randomization criteria in the experimental phase:
- Serum concentration of bevacizumab on D14 ≤ 15.5 mg/L (measured just before the 2nd
infusion of bevacizumab).
Exclusion Criteria:
Less than 6 months from the end of any prior chemotherapy, radiotherapy or adjuvant
surgery.
- 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.
- Current or recent (within 10 days of study enrollment) use of aspirin (>325 mg/day)
or clopidogrel (>75 mg/day).
- Current or recent use (within 10 days before the first dose of bevacizumab) of oral
or parenteral therapeutic anticoagulants or thrombolytic agents for therapeutic
purposes.
- Untreated CNS metastases or treatment of brain metastases, either by surgical or
radiological techniques, must have been completed more than 4 weeks before the first
study treatment.
- Surgical procedure (including open biopsy, surgical resection, wound revision, or
other major surgery involving entry into a body cavity) or significant traumatic
injury within 28 days prior to study enrollment or anticipation of study need for
major surgery during the study.
- Serious non-healing wound, active ulcer or untreated bone fracture.
- Other neoplasias (previous or current), except:
- i/ carcinoma in situ of the cervix adequately treated,
- ii/ basal cell or squamous cell carcinoma of the skin,
- iii/ cancer in complete remission for more than 5 years.
- Other illnesses, which, according to the doctor, are life-threatening to the patient
and/or which are uncontrolled.
- Primary tumor in place and symptomatic (occlusion, hemorrhage).
- Pregnant or breastfeeding women.
- Patients unable to give consent.
- Patients under guardianship, curatorship or legal protection.
Gender:
All
Minimum age:
18 Years
Maximum age:
99 Years
Healthy volunteers:
No
Start date:
October 30, 2024
Completion date:
October 30, 2029
Lead sponsor:
Agency:
University Hospital, Tours
Agency class:
Other
Collaborator:
Agency:
CHU DE BESANCON
Agency class:
Other
Collaborator:
Agency:
Gustave Roussy, Cancer Campus, Grand Paris
Agency class:
Other
Collaborator:
Agency:
CHU de Clermont-Ferrand
Agency class:
Other
Collaborator:
Agency:
CHU de Reims
Agency class:
Other
Collaborator:
Agency:
CHU de Brest
Agency class:
Other
Collaborator:
Agency:
AP-HP, Hôpital Pitié- Salpétrière
Agency class:
Other
Collaborator:
Agency:
CHU de Rouen
Agency class:
Other
Collaborator:
Agency:
Poitiers University Hospital
Agency class:
Other
Collaborator:
Agency:
Institut Paoli-Calmettes
Agency class:
Other
Collaborator:
Agency:
Rennes University Hospital
Agency class:
Other
Collaborator:
Agency:
University Hospital, Toulouse
Agency class:
Other
Collaborator:
Agency:
AP-HP, Hôpital Saint-Louis
Agency class:
Other
Collaborator:
Agency:
HCL Hôpital Edouard Hériot
Agency class:
Other
Collaborator:
Agency:
Centre Hospitalier Universitaire Dijon
Agency class:
Other
Collaborator:
Agency:
Nantes University Hospital
Agency class:
Other
Collaborator:
Agency:
Centre Hospitalier Universitaire, Amiens
Agency class:
Other
Collaborator:
Agency:
Hôpital Privé Jean Mermoz
Agency class:
Other
Collaborator:
Agency:
AP-HP, Hôpital Henri Mondor
Agency class:
Other
Collaborator:
Agency:
AP-HP, Hôpital Paul Brousse
Agency class:
Other
Collaborator:
Agency:
CHG de St-Malo
Agency class:
Other
Collaborator:
Agency:
Polyclinique de Blois
Agency class:
Other
Collaborator:
Agency:
University Hospital, Caen
Agency class:
Other
Collaborator:
Agency:
CHU de Nancy
Agency class:
Other
Source:
University Hospital, Tours
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06642844
