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

Lead sponsor

University Hospital, Tours is the lead sponsor of 304 studies on the registry; 78 are open to participants now.

Study arms

• Experimental
  Experimental: Group A

  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.

  Drug: Avastin, 25 Mg/mL Intravenous Solution

• Active comparator
  Active comparator: Group B

  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.

  Drug: Avastin, 25 Mg/mL Intravenous Solution

Interventions

• DrugAvastin, 25 Mg/mL Intravenous Solution

  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.

  Also known as: Experimental group, Control group

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 death

Secondary outcomes

1. Safety profile

   Number of Participants Who Experienced an Adverse Event (AE) per NCI-CATCAE5.0 classification

   Time frame: Up to approximately 10 months

2. 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 months

3. 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 months

4. 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 months

5. rate of secondary resection of metastases

   secondary resection of initially unresectable metastases of colorectal cancer

   Time frame: Up to approximately 10 months

6. Patient quality of life

   Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 and European Quality of Life 5 Dimensions 5 Level Version questionnaires Measure Description: The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 30 questions are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores meant a better level of function. The EQ-5D-5L is a generic tool for Patient-Reported Outcomes (PRO) measurement using 6 5 questions that can assess patients' quality of life, irrespective of the disease. . It includes a vertical EQ visual analog scale (EQ VAS, 0-100 points)

   Time frame: Up to approximately 10 months

7. Serum concentrations of bevacizumab

   Serum concentrations of bevacizumab in order to evaluate the effect of doubling the administered dose of bevacizumab.

   Time frame: on day 14 of the first administration, and at 2 months from randomization (= 3 months from the first course)

8. Medical-economic analysis

   A model-based cost-effectiveness analysis will be performed for estimating the Incremental Cost-Utility Ratio (cost per QALY gained) et the Incremental Cost-Effectiveness Ratio (cost per life-year gained) from the Healthcare system perspective.

   Time frame: up to death