BEVACIZUMAB for Metastatic colorectal cancer (unresectable)

Inclusion criteria

• {"criterion_text":"- Adult patients ≥18 years old\n- Signature of free, written and informed consent by the patient;\n- Affiliation to a French social security system.\nRandomization criteria in the experimental phase: - 1st residual serum concentration (Cres) of bevacizumab ≤ 15.5 mg/L measured just before the 2nd infusion of bevacizumab (D14).\n- ECOG Performance status (PS) 0-2\n- Having a histologically proven metastatic colorectal adenocarcinoma (on primary tumor and/or metastases) that is inoperable and well documented, i.e. not compatible with complete oncological resection at inclusion\n- For whom treatment with bevacizumab is indicated\n- For women of childbearing age: effective contraception\n- No prior treatment with palliative chemotherapy for metastatic disease (in case of adjuvant treatment, interval between the end of chemotherapy and relapse > 6 months)\n- At least one evaluable or measurable lesion assessed by computed tomography (CT) according to RECIST v1.1 criteria\n- Estimated life expectancy greater than 3 months\n- 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 strip) or ≤ 1 g/24h"}

Exclusion criteria

• {"criterion_text":"- Patient with a known contraindication to first-line chemotherapy based on bevacizumab\n- Patient under guardianship, curatorship or safeguard of justice.\n- Inadequate hematological, hepatic or renal function\n- Contraindication to bevacizumab (major surgery within 28 days, risk of arterial thrombosis, risk of bleeding, deep vein thrombosis without effective anticoagulant treatment or unbalanced anticoagulant treatment)\n- In the event of brain metastases, their treatment (surgery and/or radiotherapy) must have been completed more than 4 weeks before the first cycle of chemotherapy under study\n- Serious non-healing wound, active ulcer or untreated bone fracture: ° Other neoplasia (recent or current history), except carcinoma in situ of the cervix treated adequately, localized basal cell or squamous cell carcinoma of the skin managed with curative intent ° Neoplasia in complete remission for more than 5 years.\n- Other illness, which, according to the doctor, is life-threatening to the patient and/or which is uncontrolled\n- Primary tumor present and symptomatic (occlusion, hemorrhage)\n- Pregnant or breastfeeding women\n- Patients unable to give consent"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is progression-free survival (PFS)","definition_or_measurement_approach":"Evaluates effect of doubling the dose of bevacizumab on progression-free survival (PFS) in patients with trough serum concentration ≤ 15.5 mg/L. (PFS as stated; no additional operational definition provided in source JSON.)"}

Secondary endpoints

• {"endpoint_text":"- 1. Safety profile defined by the number of adverse events classified according to the NCI-CTCAE5.0 classification. Particularly focused on AEs which are known to be linked to bevacizumab: hypertension, proteinuria, etc.","definition_or_measurement_approach":"Safety assessed by number of AEs classified per NCI-CTCAE v5.0; specific focus on known bevacizumab-related events."}
• {"endpoint_text":"- 2. Overall survival defined as the time elapsed between the date of randomization and death (all causes),","definition_or_measurement_approach":"Overall survival measured as time from randomization to death (all causes)."}
• {"endpoint_text":"- 3. Rate of best objective tumor response according to RECIST v1.1 criteria (evaluated over the entire duration of treatment).","definition_or_measurement_approach":"Objective response rate assessed per RECIST v1.1 over entire treatment period."}
• {"endpoint_text":"- 4. Depth of tumor response defined as the percentage of tumor reduction observed at the lowest point.","definition_or_measurement_approach":"Depth of response = percentage tumor reduction at nadir."}
• {"endpoint_text":"- 5. Secondary resection of metastases (assessed over the entire treatment period)","definition_or_measurement_approach":"Rate of secondary resection of metastases assessed during treatment period."}
• {"endpoint_text":"- 6. Quality of life: EORTC QLQ-C30 and EQ5D-5L.","definition_or_measurement_approach":"QoL measured using EORTC QLQ-C30 and EQ5D-5L instruments."}
• {"endpoint_text":"- 7. Serum concentrations of bevacizumab on day 14 of the first administration, and at 2 months from randomization (= 3 months from day 1 of the first cycle).","definition_or_measurement_approach":"Bevacizumab serum concentrations measured at Day 14 of first administration and at 2 months from randomization (3 months from day 1). Centralized measurement (ELISA) by CePiBAc, CHRU de Tours as described in protocol."}
• {"endpoint_text":"- 8. Medical-economic analysis: estimation of the Differential Cost-Utility Ratio expressed as cost per QALY gained (year of life provided on quality) and the Differential Cost-Effectiveness Ratio expressed as cost per year of life gained.","definition_or_measurement_approach":"Health economic analysis estimating incremental cost-utility (cost per QALY) and cost-effectiveness (cost per life-year gained) comparing dose strategies."}

Methods

• Screening performed by investigators (assisted by clinical trial technicians) at participating centres; the study is presented to patients during a routine follow-up consultation and interested patients receive an information document prior to consenting. Inclusion visit verifies eligibility and obtains written informed consent; pre-therapeutic workup including serum pregnancy test for women is performed.
• Recruitment appears centre-based (sites listed across France); no specific online/digital or registry recruitment channels are listed in the source JSON.

France

Earliest CTIS Part Ii Submission Date

12-08-2024

Latest Decision Or Authorization Date

19-08-2024

Processing Time Days

7

Number Of Sites

20

Number Of Participants

122

Primary sponsor

Full Name

Centre Hospitalier Regional Universitaire De Tours

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France