Bevacizumab-based Chemotherapy Adapted to Bevacizumab Pharmacokinetics in 1st-line Treatment
Bevacizumab-based Chemotherapy Tailored to the Pharmacokinetics of Bevacizumab in First-line Treatment of Unresectable Metastatic Colorectal Cancer: a Randomized, Multicenter, Double-blind Phase 3 Study
University Hospital, Tours
244 participants
Mar 4, 2025
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria13
- 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 Criteria19
- 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.
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Interventions
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.
Locations(4)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06642844