Bevacizumab-based Chemotherapy Adapted to Bevacizumab Pharmacokinetics in 1st-line Treatment

Launched by UNIVERSITY HOSPITAL, TOURS · Oct 14, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a treatment for patients with unresectable metastatic colorectal cancer, which means their cancer cannot be surgically removed and has spread to other parts of the body. The focus is on using a drug called bevacizumab, combined with chemotherapy, to see how different levels of the drug in the body affect treatment outcomes. This trial is important because it aims to tailor the treatment based on how the individual patient responds to bevacizumab, potentially improving its effectiveness.

To be eligible for this trial, participants must be at least 18 years old and have a confirmed diagnosis of metastatic colorectal cancer that cannot be removed through surgery. They should not have received prior treatment for metastatic disease and must have at least one measurable tumor that doctors can assess. Participants will also need to provide written consent and meet certain health criteria. If someone joins the trial, they will receive treatment and regular monitoring to track how well the therapy is working. It's important to note that this trial is not yet recruiting, so interested patients will need to wait until it officially begins.

Gender

ALL

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.