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

NCT ID: NCT00952029

Last Updated: 2020-03-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

492 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-03-31

Study Completion Date

2018-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Maintenance with bevacizumab

FOLFIRI + Avastin and during the chemotherapy-free interval maintenance with bevacizumab

Group Type EXPERIMENTAL

bevacizumab

Intervention Type BIOLOGICAL

FOLFIRI regimen

Intervention Type DRUG

fluorouracil

Intervention Type DRUG

irinotecan hydrochloride

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

No maintenance with bevacizumab

FOLFIRI + Avastin and during the chemotherapy-free interval NO maintenance

Group Type ACTIVE_COMPARATOR

bevacizumab

Intervention Type BIOLOGICAL

FOLFIRI regimen

Intervention Type DRUG

fluorouracil

Intervention Type DRUG

irinotecan hydrochloride

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

Interventions

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bevacizumab

Intervention Type BIOLOGICAL

FOLFIRI regimen

Intervention Type DRUG

fluorouracil

Intervention Type DRUG

irinotecan hydrochloride

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas Aparicio, Pr

Role: PRINCIPAL_INVESTIGATOR

Hopital Avicenne BOBIGNY

Locations

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CH

Abbeville, , France

Site Status

Centre Radiothérapie et Oncologie de Moyenne Garonne

Agen, , France

Site Status

CHU

Amiens, , France

Site Status

Centre Paul Papin

Angers, , France

Site Status

CHU

Angers, , France

Site Status

Pringny

Annecy, , France

Site Status

CH

Aubenas, , France

Site Status

CH

Auxerre, , France

Site Status

Polyclinique Sainte Marguerite

Auxerre, , France

Site Status

CH

Avignon, , France

Site Status

Ch

Bayonne, , France

Site Status

CH

Beauvais, , France

Site Status

CHU

Besançon, , France

Site Status

Centre Pierre Curie

Beuvry, , France

Site Status

CH

Béziers, , France

Site Status

Ch

Blois, , France

Site Status

Hôpital Avicenne

Bobigny, , France

Site Status

Clinique Tivoli

Bordeaux, , France

Site Status

Institut Bergonié

Bordeaux, , France

Site Status

CH

Bourg-en-Bresse, , France

Site Status

CH

Bourges, , France

Site Status

CH

Cahors, , France

Site Status

CHIC

Castres, , France

Site Status

Hôpital Privé Sainte Marie

Chalon-sur-Saône, , France

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CH

Cholet, , France

Site Status

Clinique des Cèdres

Cornebarrieu, , France

Site Status

CH

Créteil, , France

Site Status

CH

Dax, , France

Site Status

Centre Léonard de Vinci

Dechy, , France

Site Status

Centre Leclerc

Dijon, , France

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CHU

Dijon, , France

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Parc

Dijon, , France

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CH

Dunkirk, , France

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CH

Elbeuf, , France

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CH

Fréjus, , France

Site Status

Hôpital Chicas

Gap, , France

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CH

La Roche-sur-Yon, , France

Site Status

CH

Langres, , France

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CH

Le Mans, , France

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CH

Libourne, , France

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Centre Bourgogne

Lille, , France

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Clinique F. Chenieux

Limoges, , France

Site Status

CH

Longjumeau, , France

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CHBS

Lorient, , France

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Centre Léon Bérard

Lyon, , France

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CHU Edouard Herriot

Lyon, , France

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Clinique de la Sauvegarde

Lyon, , France

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Clinique Mutualiste

Lyon, , France

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Croix Rousse

Lyon, , France

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Hôpital Saint Joseph

Lyon, , France

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CHU La Timone

Marseille, , France

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Hôpital A. Paré

Marseille, , France

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Hôpital Nord

Marseille, , France

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Hôpital Saint Joseph

Marseille, , France

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CH

Mâcon, , France

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CH

Meaux, , France

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CHG

Mont-de-Marsan, , France

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CH

Montauban, , France

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CH

Montélimar, , France

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CH Le Raincy

Montfermeil, , France

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Centre Cancérologique

Montpellier, , France

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Centre Azuréen

Mougins, , France

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Hôpital Saint Herblain

Nantes, , France

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Polyclinique

Narbonne, , France

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CH

Neuilly-sur-Seine, , France

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Centre Antoine Lacassagne

Nice, , France

Site Status

L'Archet II

Nice, , France

Site Status

CHU

Nîmes, , France

Site Status

Clinique Valdegour, Centre ONCOGARD - Institut de Cancérologie du Gard

Nîmes, , France

Site Status

CHR (Oncologie Médicale)

Orléans, , France

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CHR

Orléans, , France

Site Status

Clinique Les Murlins

Orléans, , France

Site Status

Bichat

Paris, , France

Site Status

CHU - Kremlin Bicêtre

Paris, , France

Site Status

HEGP

Paris, , France

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Hôpital Saint Louis

Paris, , France

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Pitié Salpetière

Paris, , France

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CH

Pau, , France

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CH

Perpignan, , France

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CH

Pessac, , France

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CH

Périgueux, , France

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CH

Rang-du-Fliers, , France

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CH

Reims, , France

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CH

Romans-sur-Isère, , France

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CH

Roubaix, , France

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CHU

Rouen, , France

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CH

Saint-Brieuc, , France

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Clinique Armoricaine

Saint-Brieuc, , France

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HIA Begin

Saint-Mandé, , France

Site Status

Centre Joliot Curie

Saint-Martin-Boulogne, , France

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Clinique Mutualiste

Saint-Nazaire, , France

Site Status

CHU Saint Etienne

Saint-Priest-en-Jarez, , France

Site Status

Centre Paul Strauss

Strasbourg, , France

Site Status

CHU Trousseau

Tours, , France

Site Status

CH

Valence, , France

Site Status

Clinique Générale

Valence, , France

Site Status

CH

Valenciennes, , France

Site Status

CAC

Vandœuvre-lès-Nancy, , France

Site Status

CH Bretagne Atlantique

Vannes, , France

Site Status

Clinique

Vienne, , France

Site Status

CH

Villejuif, , France

Site Status

Hôpital Intercommunal

Villeneuve-Saint-Georges, , France

Site Status

Countries

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France

References

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Aparicio T, Linot B, Le Malicot K, Bouche O, Boige V, Francois E, Ghiringhelli F, Legoux JL, Ben Abdelghani M, Phelip JM, Faroux R, Dahan L, Taieb J, Bedenne L. FOLFIRI+bevacizumab induction chemotherapy followed by bevacizumab or observation in metastatic colorectal cancer, a phase III trial (PRODIGE 9--FFCD 0802). Dig Liver Dis. 2015 Apr;47(4):271-2. doi: 10.1016/j.dld.2015.01.146. Epub 2015 Jan 20. No abstract available.

Reference Type BACKGROUND
PMID: 25677925 (View on PubMed)

Aparicio T, Ghiringhelli F, Boige V, Le Malicot K, Taieb J, Bouche O, Phelip JM, Francois E, Borel C, Faroux R, Dahan L, Jacquot S, Genet D, Khemissa F, Suc E, Desseigne F, Texereau P, Lepage C, Bennouna J; PRODIGE 9 Investigators. Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9). J Clin Oncol. 2018 Mar 1;36(7):674-681. doi: 10.1200/JCO.2017.75.2931. Epub 2018 Jan 18.

Reference Type RESULT
PMID: 29346040 (View on PubMed)

Aparicio T, Bennouna J, Le Malicot K, Boige V, Taieb J, Bouche O, Phelip JM, Francois E, Borel C, Faroux R, Dahan L, Bachet JB, Egreteau J, Kaminsky MC, Gornet JM, Cojocarasu O, Gasmi M, Guerin-Meyer V, Lepage C, Ghiringhelli F; for PRODIGE investigators/collaborators. Predictive factors for early progression during induction chemotherapy and chemotherapy-free interval: analysis from PRODIGE 9 trial. Br J Cancer. 2020 Mar;122(7):957-962. doi: 10.1038/s41416-020-0735-8. Epub 2020 Feb 4.

Reference Type RESULT
PMID: 32015513 (View on PubMed)

Guilloteau A, Abrahamowicz M, Boussari O, Jooste V, Aparicio T, Quantin C, Le Malicot K, Binquet C. Impact of time-varying cumulative bevacizumab exposures on survival: re-analysis of data from randomized clinical trial in patients with metastatic colo-rectal cancer. BMC Med Res Methodol. 2021 Jan 9;21(1):14. doi: 10.1186/s12874-020-01202-9.

Reference Type DERIVED
PMID: 33422006 (View on PubMed)

Dohan A, Gallix B, Guiu B, Le Malicot K, Reinhold C, Soyer P, Bennouna J, Ghiringhelli F, Barbier E, Boige V, Taieb J, Bouche O, Francois E, Phelip JM, Borel C, Faroux R, Seitz JF, Jacquot S, Ben Abdelghani M, Khemissa-Akouz F, Genet D, Jouve JL, Rinaldi Y, Desseigne F, Texereau P, Suc E, Lepage C, Aparicio T, Hoeffel C; PRODIGE 9 Investigators and PRODIGE 20 Investigators. Early evaluation using a radiomic signature of unresectable hepatic metastases to predict outcome in patients with colorectal cancer treated with FOLFIRI and bevacizumab. Gut. 2020 Mar;69(3):531-539. doi: 10.1136/gutjnl-2018-316407. Epub 2019 May 17.

Reference Type DERIVED
PMID: 31101691 (View on PubMed)

Other Identifiers

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FFCD-PRODIGE-9

Identifier Type: -

Identifier Source: secondary_id

FFCD-0802

Identifier Type: -

Identifier Source: secondary_id

EU-20912

Identifier Type: -

Identifier Source: secondary_id

EU-21030

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2008-007928-25

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2009-017996-11

Identifier Type: -

Identifier Source: secondary_id

PRODIGE 9

Identifier Type: -

Identifier Source: org_study_id

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