Combination Chemotherapy and Bevacizumab With or Without Bevacizumab Maintenance Therapy in Treating Patients With Metastatic Colorectal Cancer

March 27, 2020 updated by: Federation Francophone de Cancerologie Digestive

Multicenter Phase III Randomized Study of FOLFIRI Plus Bevacizumab Following or Not by a Maintenance Therapy With Bevacizumab in Patients With Non-Pretreated Metastatic Colorectal Cancer

RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab may stop the growth of colorectal cancer by blocking blood flow to the tumor. It is not yet known whether giving more than one drug (combination chemotherapy) is more effective when given with or without bevacizumab in treating patients with metastatic colorectal cancer.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy with or without bevacizumab to see how well it works in treating patients with metastatic colorectal cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Compare disease-control duration in patients with metastatic colorectal cancer receiving FOLFIRI chemotherapy in combination with bevacizumab with or without bevacizumab maintenance therapy.

Secondary

  • Determine objective response rate.
  • Determine non-hematologic grade 3-4 (except alopecia) toxicity rate.
  • Determine overall toxicity rate.
  • Determine duration of chemotherapy-free interval.
  • Determine progression-free survival.
  • Determine overall survival.
  • Determine time-to-treatment failure.
  • Determine quality of life (EORTC QLQ-C30).
  • Complete geriatric evaluation.

OUTLINE: This is a multicenter study. Patients are stratified according to cancer center, primary tumor (resected vs unresected), and Köhne criteria (low vs intermediate vs high). Patients are randomized to 1 of 2 treatment arms.

  • Arm A: Patients receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1-2. Chemotherapy treatment repeats every 2 weeks for 12 courses. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks during chemotherapy. Patients then receive bevacizumab maintenance therapy once every 2 weeks during the chemotherapy-free interval.
  • Arm B: Patients receive FOLFIRI chemotherapy and bevacizumab as in arm A. Patients receive no treatment during the chemotherapy-free interval.

In all arms, the chemotherapy treatment and the chemotherapy-free interval treatment repeats in the absence of disease progression during the chemotherapy portion or unacceptable toxicity. Patients who progress during the chemotherapy-free interval will receive 12 more courses of chemotherapy.

All patients complete quality of life questionnaires (QLQ-30) and patients ≥ 75 also complete the geriatric questionnaire at baseline and every 8 weeks during study treatment.

After completion of study treatment, patients are followed up every 8 weeks.

Study Type

Interventional

Enrollment (Actual)

492

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Abbeville, France
        • CH
      • Agen, France
        • Centre Radiothérapie et Oncologie de Moyenne Garonne
      • Amiens, France
        • CHU
      • Angers, France
        • CHU
      • Angers, France
        • Centre Paul Papin
      • Annecy, France
        • Pringny
      • Aubenas, France
        • CH
      • Auxerre, France
        • CH
      • Auxerre, France
        • Polyclinique Sainte marguerite
      • Avignon, France
        • CH
      • Bayonne, France
        • CH
      • Beauvais, France
        • CH
      • Besançon, France
        • CHU
      • Beuvry, France
        • Centre Pierre Curie
      • Blois, France
        • CH
      • Bobigny, France
        • Hôpital Avicenne
      • Bordeaux, France
        • Institut Bergonié
      • Bordeaux, France
        • Clinique Tivoli
      • Bourg en Bresse, France
        • CH
      • Bourges, France
        • CH
      • Béziers, France
        • CH
      • Cahors, France
        • CH
      • Castres, France
        • CHIC
      • Chalon sur Saone, France
        • Hôpital privé sainte Marie
      • Cholet, France
        • CH
      • Cornebarrieu, France
        • Clinique des Cèdres
      • Creteil, France
        • CH
      • Dax, France
        • CH
      • Dechy, France
        • Centre Léonard de Vinci
      • Dijon, France
        • CHU
      • Dijon, France
        • Centre Leclerc
      • Dijon, France
        • PARC
      • Dunkerque, France
        • CH
      • Elbeuf, France
        • CH
      • Frejus, France
        • CH
      • Gap, France
        • Hôpital Chicas
      • La Roche sur Yon, France
        • CH
      • Langres, France
        • CH
      • Le Mans, France
        • CH
      • Libourne, France
        • CH
      • Lille, France
        • Centre Bourgogne
      • Limoges, France
        • Clinique F. Chenieux
      • Longjumeau, France
        • CH
      • Lorient, France
        • CHBS
      • Lyon, France
        • Centre Léon Bérard
      • Lyon, France
        • Chu Edouard Herriot
      • Lyon, France
        • Clinique de la Sauvegarde
      • Lyon, France
        • Clinique Mutualiste
      • Lyon, France
        • Croix Rousse
      • Lyon, France
        • Hopital Saint Joseph
      • Macon, France
        • CH
      • Marseille, France
        • CHU La Timone
      • Marseille, France
        • Hopital Nord
      • Marseille, France
        • Hopital Saint Joseph
      • Marseille, France
        • Hôpital A. Paré
      • Meaux, France
        • CH
      • Mont de Marsan, France
        • CHG
      • Montauban, France
        • CH
      • Montelimar, France
        • CH
      • Montfermeil, France
        • Ch Le Raincy
      • Montpellier, France
        • Centre Cancérologique
      • Mougins, France
        • Centre Azuréen
      • Nantes, France
        • Hôpital Saint Herblain
      • Narbonne, France
        • Polyclinique
      • Neuilly sur Seine, France
        • CH
      • Nice, France
        • Centre Antoine Lacassagne
      • Nice, France
        • L'Archet II
      • Nimes, France
        • CHU
      • Nimes, France
        • Clinique Valdegour, Centre ONCOGARD - Institut de Cancérologie du Gard
      • Orléans, France
        • CHR
      • Orléans, France
        • CHR (Oncologie Médicale)
      • Orléans, France
        • Clinique Les Murlins
      • Paris, France
        • HEGP
      • Paris, France
        • Hôpital Saint Louis
      • Paris, France
        • BICHAT
      • Paris, France
        • CHU - Kremlin Bicêtre
      • Paris, France
        • Pitié Salpêtière
      • Pau, France
        • CH
      • Perigueux, France
        • CH
      • Perpignan, France
        • CH
      • Pessac, France
        • CH
      • Rang Du Fliers, France
        • CH
      • Reims, France
        • CH
      • Romans sur Isere, France
        • CH
      • Roubaix, France
        • CH
      • Rouen, France
        • CHU
      • Saint Brieuc, France
        • CH
      • Saint Mande, France
        • HIA Begin
      • Saint Nazaire, France
        • Clinique Mutualiste
      • Saint Priest en Jarez, France
        • CHU Saint Etienne
      • Saint-Brieuc, France
        • Clinique Armoricaine
      • Saint-Martin-Boulogne, France
        • Centre Joliot Curie
      • Strasbourg, France
        • Centre Paul Strauss
      • Tours, France
        • CHU Trousseau
      • Valence, France
        • CH
      • Valence, France
        • Clinique Générale
      • Valenciennes, France
        • CH
      • Vandoeuvre Les Nancy, France
        • CAC
      • Vannes, France
        • CH Bretagne Atlantique
      • Vienne, France
        • Clinique
      • Villejuif, France
        • CH
      • Villeneuve Saint Georges, France
        • Hopital Intercommunal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal cancer

    • Metastatic disease
  • Not a candidate for curative surgery
  • At least 1 tumor target measurable by RECIST criteria
  • No metastasis potentially resectable after receiving chemotherapy
  • No occlusive tumors
  • No macronodular peritoneal carcinomatosis
  • No known or suspected CNS metastases

PATIENT CHARACTERISTICS:

  • OMS status 0-2
  • Life expectancy ≥ 3 months
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN in the presence of hepatic metastases)
  • Creatinine ≤ 1.5 times ULN
  • Proteinuria ≤1 g
  • Not pregnant or nursing
  • No gastroduodenal ulcer, wound, or fractured bone
  • No acute or subacute intestinal occlusion or history of inflammatory bowel disease or large resection of small bowel
  • No clinically relevant coronary artery disease or a history of a myocardial infarction within the last 6 months
  • No uncontrolled hypertension while receiving chronic medication
  • No other malignancy within the past 5 years except for basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
  • No medical or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study

PRIOR CONCURRENT THERAPY:

  • See Patient Characteristics

  • No prior chemotherapy for metastatic disease

    • Adjuvant chemotherapy allowed provided it was completed > 6 months ago
  • No prior irinotecan or other antiangiogenic therapy
  • At least 4 weeks since surgery (except for diagnostic biopsy) or irradiation
  • No other drugs not allowed for medical reasons

  • Concurrent oral anticoagulants (e.g., coumadin, warfarin) allowed provided the INR is closely monitored

    • A change of anticoagulants to low-molecular weight heparin is preferred

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval maintenance with bevacizumab
Drug: fluorouracil
Drug: leucovorin calcium
Drug: irinotecan hydrochloride
Biological: bevacizumab
Drug: FOLFIRI regimen
ACTIVE_COMPARATOR: No maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval NO maintenance
Drug: fluorouracil
Drug: leucovorin calcium
Drug: irinotecan hydrochloride
Biological: bevacizumab
Drug: FOLFIRI regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Disease-control duration
Time Frame: one year after last patient included
one year after last patient included

Secondary Outcome Measures

Outcome Measure
Time Frame
Objective response rate
Time Frame: one year after last patient is included
one year after last patient is included
Rate of non-hematologic grade 3-4 toxicities (except alopecia)
Time Frame: one year after last patient is included
one year after last patient is included
Overall toxicity rate
Time Frame: one year after last patient is included
one year after last patient is included
Duration of chemotherapy-free interval
Time Frame: one year after last patient is included
one year after last patient is included
Progression-free survival
Time Frame: one year after last patient is included
one year after last patient is included
Overall survival
Time Frame: one and 2 year after last patient is included
one and 2 year after last patient is included
Time-to-treatment failure
Time Frame: one year after last patient is included
one year after last patient is included
Quality of life as assessed by EORTC QLQ-C30
Time Frame: one year after last patient is included
one year after last patient is included
Geriatric evaluation
Time Frame: one year after last patient is included
one year after last patient is included

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federation Francophone de Cancerologie Digestive

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (ACTUAL)

December 1, 2015

Study Completion (ACTUAL)

January 1, 2018

Study Registration Dates

First Submitted

August 1, 2009

First Submitted That Met QC Criteria

August 1, 2009

First Posted (ESTIMATE)

August 4, 2009

Study Record Updates

Last Update Posted (ACTUAL)

March 30, 2020

Last Update Submitted That Met QC Criteria

March 27, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRODIGE 9
  • FFCD-PRODIGE-9
  • FFCD-0802
  • EU-20912
  • EU-21030
  • EUDRACT-2008-007928-25
  • EUDRACT-2009-017996-11

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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