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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00952029
• Other study ID #: PRODIGE 9
• Secondary ID: FFCD-PRODIGE-9FF
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 2010
• Est. completion date: January 2018

Study information

• Verified date: March 2020
• Source: Federation Francophone de Cancerologie Digestive
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 492
• Est. completion date: January 2018
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• bevacizumab

Drug:
• FOLFIRI regimen

• fluorouracil

• irinotecan hydrochloride

• leucovorin calcium

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive

Country where clinical trial is conducted

France, 

References & Publications (3)

Aparicio T, Bennouna J, Le Malicot K, Boige V, Taieb J, Bouché O, Phelip JM, François 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/ — View Citation

Aparicio T, Ghiringhelli F, Boige V, Le Malicot K, Taieb J, Bouché O, Phelip JM, François 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 — View Citation

Aparicio T, Linot B, Le Malicot K, Bouché O, Boige V, François 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-control duration		one year after last patient included
Secondary	Objective response rate		one year after last patient is included
Secondary	Rate of non-hematologic grade 3-4 toxicities (except alopecia)		one year after last patient is included
Secondary	Overall toxicity rate		one year after last patient is included
Secondary	Duration of chemotherapy-free interval		one year after last patient is included
Secondary	Progression-free survival		one year after last patient is included
Secondary	Overall survival		one and 2 year after last patient is included
Secondary	Time-to-treatment failure		one year after last patient is included
Secondary	Quality of life as assessed by EORTC QLQ-C30		one year after last patient is included
Secondary	Geriatric evaluation		one year after last patient is included