Back to resultsA Randomized Phase III Study Comparing Maintenance Treatment With Fluoropyrimidine + Bevacizumab Versus Fluoropyrimidine After Induction Chemotherapy for a Metastatic Colorectal Cancer (BEVAMAINT)
Primary Purpose
Metastatic Colorectal Cancer
Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Fluoropyrimidine
Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic 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
Sites / Locations
- Chu Dijon BourgogneRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Fluoropyrimidine
Fluoropyrimidine + Bevacizumab
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Progression-free survival (PFS1)
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 (PFS2)
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)
Defined as the time between randomization and death (any cause). Patients alive will be censored at the date of last news.
Safety
Toxicities will be graded according to the NCI-CTC v 4.0 criteria before each cycle.
Quality of Life (QoL)
Assessed at each evaluation with a questionnaire
Full Information
NCT ID
NCT04188145
First Posted
December 3, 2019
Last Updated
October 21, 2021
Sponsor
Centre Hospitalier Universitaire Dijon
1. Study Identification
Unique Protocol Identification Number
NCT04188145
Brief Title
A Randomized Phase III Study Comparing Maintenance Treatment With Fluoropyrimidine + Bevacizumab Versus Fluoropyrimidine After Induction Chemotherapy for a Metastatic Colorectal Cancer
Acronym
BEVAMAINT
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
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Recruiting
Study Start Date
January 27, 2020 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire Dijon
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
400 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Fluoropyrimidine
Arm Type
Active Comparator
Arm Title
Fluoropyrimidine + Bevacizumab
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Fluoropyrimidine
Intervention Description
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
Intervention Name(s)
Bevacizumab
Intervention Description
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
Primary Outcome Measure Information:
Title
The Time-to-Treatment Failure (TTF)
Description
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.
Time Frame
8 months
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS1)
Description
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.
Time Frame
16 months
Title
Progression-free survival (PFS2)
Description
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.
Time Frame
16 months
Title
Overall Survival (OS)
Description
Defined as the time between randomization and death (any cause). Patients alive will be censored at the date of last news.
Time Frame
3 years
Title
Safety
Description
Toxicities will be graded according to the NCI-CTC v 4.0 criteria before each cycle.
Time Frame
3 years
Title
Quality of Life (QoL)
Description
Assessed at each evaluation with a questionnaire
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thomas Aparicio
Phone
(0)1 42 49 95 97
Ext
+33
Email
thomas.aparicio@aphp.fr
Facility Information:
Facility Name
Chu Dijon Bourgogne
City
Dijon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sylvain MANFREDI
Phone
(0)3 80 29 37 50
Ext
+33
Email
sylvain.manfredi@chu-dijon.fr
12. IPD Sharing Statement
Learn more about this trial
A Randomized Phase III Study Comparing Maintenance Treatment With Fluoropyrimidine + Bevacizumab Versus Fluoropyrimidine After Induction Chemotherapy for a Metastatic Colorectal Cancer
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