A Randomized Phase III Study Comparing Maintenance Treatment With Fluoropyrimidine + Bevacizumab Versus Fluoropyrimidine After Induction Chemotherapy for a Metastatic Colorectal Cancer (BEVAMAINT)

University Hospital Center (CHU) Dijon Bourgogne

Status and phase

Enrolling

Phase 3

Conditions

Metastatic Colorectal Cancer

Treatments

Drug: Fluoropyrimidine

Drug: Bevacizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT04188145

PRODIGE 71

Details and patient eligibility

About

The aim of BEVAMAINT is to improve benefic effect of maintenance therapy after a first line of induction chemotherapy for patients with colorectal cancer

Enrollment

400 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically confirmed metastatic colorectal adenocarcinoma before induction treatment
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) or IAH chemotherapy
Life expectancy > 3 months
Age ≥ 18 years
Patient is at least 4 weeks from any major surgery
Total bilirubin < 25 µmol/L, ASAT < 3 x ULN, ALAT < 3 x ULN (ASAT , ALAT < 5 x ULN in case of hepatic metastasis) , PT >60% , PAL<2.5 x ULN ( < 5 x ULN in case of hepatic metastasis) - 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 or ≤1g/24hour 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 premenopausal female patients
Male and female patients of childbearing potential agree to use a highly effective contraceptive measure
Patient affiliated to a social security system

Exclusion criteria

Myocardial infarction, severe coronaropathy or severe cardiac dysfunction less than 6 months prior randomization
Follow-up impossible
Patients with all metastases resected (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 >140 mmHg and/or diastolic blood pressure >90 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 according to the updated SmPC
Intestinal perforation or intestinal fistula
Previous or active gastrointestinal bleeding
Thromboembolic event and/or history of thromboembolic event
Severe hepatic insufficiency