Unresectable metastatic colorectal cancer with measurable hepatic lesions (according to RECIST V1.1) MedDRA version: 21.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: AVASTIN
Product Name: BEVACIZUMAB
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Concentration unit: mg/kg milligram(s)/kilogram
Concen
Sponsors
Centre Hospitalier Universitaire (CHU) de Dijon
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically confirmed metastatic colorectal adenocarcinoma - Measurable or non-measurable lesion before the induction treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) - Metastatic, unresectable disease according local practice after induction treatment - ECOG performance status = 2 - Disease control (complete response, partial response or stable disease) after 4-6 months of frontline induction chemotherapy with doublet (fluoropyrimidine + irinotecan or oxaliplatin) or triplet (fluoropyrimidine + irinotecan + oxaliplatin) +/- (cetuximab, panitumumab, bevacizumab, aflibercept or others targeted therapy, or IAH chemotherapy - Life expectancy > 3 months - Age = 18 years - Patient is at least 4 weeks from any major surgery - Neutrophils > 1500/mm3, platelets > 100 000/mm3, haemoglobin = 9 g/dL - Creatinin clearance > 30 ml/min (MDRD) – if creatinin clearance comprised between 30 and 50 ml/min, see smPCs for dose adjustments - Proteinuria = 2+ (dipstick urinalysis) (if more than 2+, so proteinuria at 24 hours must be = 1g) - Patient is able to understand, sign, and date the written informed consent - Evidence of post-menopausal status or negative urinary or serum pregnancy test for pre-menopausal female patients - Male and female patients of childbearing potential agree to use a highly effective contraceptive measure - Patient affiliated to a social security system Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: - Myocardial infarction less than 6 months, severe coronaropathy or severe cardiac dysfunction - Follow-up impossible - Patients with totally resected metastases (R0/R1) after induction chemotherapy - Patient with a hand-foot syndrome > 1 before maintenance treatment - Known brain or leptomeningeal metastases - Other concomitant or previous malignancy, except: adequately treated in situ carcinoma in complete remission for >5 years - Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy - Pregnancy or breast feeding - Treatment with sorivudine or analogs (brivudine) - Treatment with phenytoin or analogs - Partial or complete DPD deficiency (Uracilemia = 16 ng/ml) - Peptic ulcer not healed after treatment - Any contraindication to bevacizumab or fluoropyrimidine treatments
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare efficacy maintenance therapy (i.e. Time to Treatment Failure) with bevacizumab + fluoropyrimidine versus fluoropyrimidine alone after induction chemotherapy (with doublet (fluoropyrimidine or TAS102 + irinotecan or oxaliplatin) or triplet (fluoropyrimidine + irinotecan + oxaliplatin) +/- cetuximab, panitumumab, bevacizumab, aflibercept or others targeted therapy, or IAH chemotherapy.;Secondary Objective: -Toxicity according NCI-CTC v4.0 -Quality of life (according QLQ-C30) -Progression-free survival (PFS1) – according investigator and centralized review (RECIST V1.1) -Progression-free survival 2 (PFS2) -Overall survival (OS);Primary end point(s): The Time-to-Treatment Failure (TTF) will be calculated from date of randomization (after the end of induction chemotherapy) to first radiological progression (according to RECIST 1.1) or death or start of a new chemotherapy (induction regimen or second line) or end of maintenance treatment without further chemotherapy, even if there is no radiological progression. Patients alive with no radiological progression and under maintenance treatment will be censored at the date of last news.;Timepoint(s) of evaluation of this end point: The Time-to-treatment failure (TTF) is estimated at 1 year after the last patient is randomized. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety profile Toxicities will be graded according to the NCI-CTC v 4.0 criteria before each cycle. Quality of life (QoL) QoL will be assessed at each evaluation with QLQ-C30 questionnaire. Progression-free survival (PFS1): PFS1 is defined as the time between randomization and the first radiological progression (according to RECIST 1.1) or death (whatever occurs first). Patients alive and without progression will be censored at the date of last news. Progression-free survival 2 (PFS2): PFS2 is defined as the time between the end of maintenance treatment (whatever the reason is) and the radiological progression after this end of maintenance treatment or death whatever the cause. Patients alive and without progression will be censored at the date of last news. Overall Survival (OS): OS is defined as the time between randomization and death (any cause). Patients alive will be censored at the date of last news.;Timepoint(s) of evaluation of this end point: All these endoints will be evaluated at 2 years after the last patient is randomised. Overall survival can be re-evaluated later. | — |
Countries
France
Contacts
Public ContactDaniel Gonzalez
Fédération Francophone de Cancérologie Digestive (FFCD)
Outcome results
None listed