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

NCT ID: NCT04188145

Last Updated: 2021-10-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-27
• Study Completion Date: 2025-12-31

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

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fluoropyrimidine

Group Type: ACTIVE_COMPARATOR

Fluoropyrimidine

Intervention Type: DRUG

Option 1: Capecitabine 1250 mg/m2 twice daily (i.e. 2500 mg/m²/d) (D1 to D14, D1 = D22) For frail patients according to investigator evaluation capecitabine dose may be reduced to 1000 mg/m2 twice daily (2000 mg/m²/d).

Or Option 2: Capecitabine 625 mg/m2 twice daily (i.e. 1250 mg/m²/d) (D1 to D21, D1 = D22) Or Option 3: LV5FU2 simplified (folinic acid 200 mg/m² (or Elvorin 400 mg/m²) IV during 2h followed by 5-FU bolus IV of 400 mg/m² during 10 min and IV continuous 5-FU at 2400 mg/m² during 46h). (D1=D15).

Fluoropyrimidine + Bevacizumab

Group Type: ACTIVE_COMPARATOR

Fluoropyrimidine

Intervention Type: DRUG

Option 1: Capecitabine 1250 mg/m2 twice daily (i.e. 2500 mg/m²/d) (D1 to D14, D1 = D22) For frail patients according to investigator evaluation capecitabine dose may be reduced to 1000 mg/m2 twice daily (2000 mg/m²/d).

Or Option 2: Capecitabine 625 mg/m2 twice daily (i.e. 1250 mg/m²/d) (D1 to D21, D1 = D22) Or Option 3: LV5FU2 simplified (folinic acid 200 mg/m² (or Elvorin 400 mg/m²) IV during 2h followed by 5-FU bolus IV of 400 mg/m² during 10 min and IV continuous 5-FU at 2400 mg/m² during 46h). (D1=D15).

Bevacizumab

Intervention Type: DRUG

Option 1 and Option 2 : D1 bevacizumab 7.5 mg/kg IV (D1=D21). See smPCs for infusion time of bevacizumab.

Or Option 3: D1 bevacizumab 5 mg/kg IV (D1=D15). See smPCs for infusion time of bevacizumab

Interventions

Fluoropyrimidine

Option 1: Capecitabine 1250 mg/m2 twice daily (i.e. 2500 mg/m²/d) (D1 to D14, D1 = D22) For frail patients according to investigator evaluation capecitabine dose may be reduced to 1000 mg/m2 twice daily (2000 mg/m²/d).

Or Option 2: Capecitabine 625 mg/m2 twice daily (i.e. 1250 mg/m²/d) (D1 to D21, D1 = D22) Or Option 3: LV5FU2 simplified (folinic acid 200 mg/m² (or Elvorin 400 mg/m²) IV during 2h followed by 5-FU bolus IV of 400 mg/m² during 10 min and IV continuous 5-FU at 2400 mg/m² during 46h). (D1=D15).

Intervention Type: DRUG

Bevacizumab

Option 1 and Option 2 : D1 bevacizumab 7.5 mg/kg IV (D1=D21). See smPCs for infusion time of bevacizumab.

Or Option 3: D1 bevacizumab 5 mg/kg IV (D1=D15). See smPCs for infusion time of bevacizumab

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire Dijon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Chu Dijon Bourgogne

Dijon, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Thomas Aparicio

Role: CONTACT

Phone: (0)1 42 49 95 97

Email: thomas.aparicio@aphp.fr

Facility Contacts

Sylvain MANFREDI

Role: primary

Other Identifiers

PRODIGE 71

Identifier Type: -

Identifier Source: org_study_id