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

Sponsor
Centre Hospitalier Universitaire Dijon (Other)
Overall Status
Recruiting
CT.gov ID
NCT04188145
Collaborator
(none)
400
1
2
70.1
5.7

Study Details

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

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
400 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase III Study Comparing Maintenance Treatment With Fluoropyrimidine + Bevacizumab Versus Fluoropyrimidine After Induction Chemotherapy for a Metastatic Colorectal Cancer
Actual Study Start Date :
Jan 27, 2020
Anticipated Primary Completion Date :
Sep 1, 2023
Anticipated Study Completion Date :
Dec 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Fluoropyrimidine

Drug: 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).

Active Comparator: Fluoropyrimidine + Bevacizumab

Drug: 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).

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

Outcome Measures

Primary Outcome Measures

  1. The Time-to-Treatment Failure (TTF) [8 months]

    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

  1. Progression-free survival (PFS1) [16 months]

    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.

  2. Progression-free survival (PFS2) [16 months]

    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.

  3. Overall Survival (OS) [3 years]

    Defined as the time between randomization and death (any cause). Patients alive will be censored at the date of last news.

  4. Safety [3 years]

    Toxicities will be graded according to the NCI-CTC v 4.0 criteria before each cycle.

  5. Quality of Life (QoL) [3 years]

    Assessed at each evaluation with a questionnaire

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Chu Dijon Bourgogne Dijon France

Sponsors and Collaborators

  • Centre Hospitalier Universitaire Dijon

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Centre Hospitalier Universitaire Dijon
ClinicalTrials.gov Identifier:
NCT04188145
Other Study ID Numbers:
  • PRODIGE 71
First Posted:
Dec 5, 2019
Last Update Posted:
Oct 28, 2021
Last Verified:
Oct 1, 2021
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 28, 2021