Clinical trial NCT04188145: A Randomized Phase III Study Comparing Maintenance Treatment With Fluoropyrimidine + Bevacizumab Versus Fluoropyrimidine After Induction Chemotherapy for a Metastatic Colorectal Cancer
Official title: A Randomized Phase III Study Comparing Maintenance Treatment With Fluoropyrimidine + Bevacizumab Versus Fluoropyrimidine After Induction Chemotherapy for a Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
First posted: 2019-12-05
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: The Time-to-Treatment Failure (TTF)
timeFrame: 8 months
Secondary outcomes:
measure: Progression-free survival (PFS1)
timeFrame: 16 months
measure: Progression-free survival (PFS2)
timeFrame: 16 months
measure: Overall Survival (OS)
timeFrame: 3 years
measure: Safety
timeFrame: 3 years
measure: Quality of Life (QoL)
timeFrame: 3 years
Other outcomes:
Locations:
city: Dijon
country: France
facility: Chu Dijon Bourgogne
Study officials:
References: