A Study of Avastin (Bevacizumab) Plus Crossover Fluoropyrimidine-Based Chemotherapy in Patients With Metastatic Colorectal Cancer.

NCT ID: NCT00700102

Last Updated: 2015-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 820 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2013-05-31

Brief Summary

This study will evaluate the efficacy and safety of adding bevacizumab to crossover fluoropyrimidine-based chemotherapy in patients with metastatic colorectal cancer who have experienced disease progression under first line treatment with standard chemotherapy plus bevacizumab. Participants will receive chemotherapy alone, or in combination with bevacizumab. The anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. Participants are allowed to continue on bevacizumab, even after stopping chemotherapy.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemotherapy

Chemotherapy alone until disease progression, unacceptable toxicity, or patient refusal

Group Type: ACTIVE_COMPARATOR

Chemotherapy

Intervention Type: DRUG

As prescribed

Chemotherapy + Bevacizumab

Chemotherapy and Bevacizumab until disease progression, unacceptable toxicity, or patient refusal

Group Type: EXPERIMENTAL

Chemotherapy

Intervention Type: DRUG

As prescribed

Bevacizumab

Intervention Type: DRUG

Bevacizumab, 5 mg/kg intravenously (IV) on days 1 and 14 of each 4 week cycle, or 7.5 mg/kg IV on days 1 and 22 of each 6 week cycle.

Interventions

Chemotherapy

As prescribed

Intervention Type: DRUG

Bevacizumab

Bevacizumab, 5 mg/kg intravenously (IV) on days 1 and 14 of each 4 week cycle, or 7.5 mg/kg IV on days 1 and 22 of each 6 week cycle.

Intervention Type: DRUG

Other Intervention Names

Avastin

Eligibility Criteria

Inclusion Criteria

• Adult patients, >=18 years of age
• Metastatic colorectal cancer and disease progression
• Previously treated with first-line chemotherapy plus Avastin
• Eastern Cooperative Oncology Group (ECOG) performance status <=2.

Exclusion Criteria

• Diagnosis of progression of disease more than 3 months after last Avastin administration
• First-line patients with progression-free survival in first-line of <3 months
• Patients receiving less than 3 consecutive months of Avastin in first-line therapy
• Past or current history (within the last 2 years prior to treatment start) of other malignancies, except for curatively treated basal and squamous cell cancer of the skin or in situ cancer of the cervix
• Clinically significant cardiovascular disease within 6 months prior to start of study treatment
• Known central nervous system (CNS) disease, except for treated CNS metastases as defined by protocol

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Dornbirn, , Austria

Fürstenfeld, , Austria

Graz, , Austria

Graz, , Austria

Hall in Tirol, , Austria

Innsbruck, , Austria

Krems, , Austria

Leoben, , Austria

Linz, , Austria

Rankweil, , Austria

Ried-innkreis, , Austria

Salzburg, , Austria

Sankt Pölten, , Austria

Sankt Veit an der Glan, , Austria

Steyr, , Austria

Vienna, , Austria

Villach, , Austria

Waidhofen A D Thaya, , Austria

Wels, , Austria

Wiener Neustadt, , Austria

Aalst, , Belgium

Assebroek, , Belgium

La Louvière, , Belgium

Leuven, , Belgium

Liège, , Belgium

Turnhout, , Belgium

Brno, , Czechia

Olomouc, , Czechia

Prague, , Czechia

Prague, , Czechia

Copenhagen, , Denmark

Esbjerg, , Denmark

Herlev, , Denmark

Herning, , Denmark

Hillerød, , Denmark

Næstved, , Denmark

Tallinn, , Estonia

Tallinn, , Estonia

Tartu, , Estonia

Helsinki, , Finland

Oulu, , Finland

Tampere, , Finland

Turku, , Finland

Vaasa, , Finland

Agen, , France

Albi, , France

Amiens, , France

Amilly, , France

Antibes, , France

Antony, , France

Arras, , France

Avignon, , France

Besançon, , France

Béziers, , France

Bordeaux, , France

Bordeaux, , France

Bourgoin, , France

Caen, , France

Cahors, , France

Chambray-lès-Tours, , France

Clermont-Ferrand, , France

Colmar, , France

Compiègne, , France

Dechy, , France

Dijon, , France

Grenoble, , France

La Roche-sur-Yon, , France

La Seyne-sur-Mer, , France

Lagny-sur-Marne, , France

Le Kremlin-Bicêtre, , France

Le Mans, , France

Libourne, , France

Lille, , France

Lille, , France

Limoges, , France

Lliie, , France

Longjumeau, , France

Lyon, , France

Lyon, , France

Lyon, , France

Marseille, , France

Marseille, , France

Marseille, , France

Mâcon, , France

Meaux, , France

Metz, , France

Mont-de-Marsan, , France

Montbéliard, , France

Montfermeil, , France

Montpellier, , France

Mougins, , France

Nancy, , France

Nantes, , France

Nantes, , France

Neuilly-sur-Seine, , France

Nevers, , France

Nice, , France

Orléans, , France

Paris, , France

Paris, , France

Paris, , France

Paris, , France

Paris, , France

Paris, , France

Pessac, , France

Périgueux, , France

Pierre-Bénite, , France

Pontoise, , France

Reims, , France

Reims, , France

Rennes, , France

Rodez, , France

Rouen, , France

Saint-Brieuc, , France

Saint-Cloud, , France

Saint-Grégoire, , France

Saint-Herblain, , France

Saint-Nazaire, , France

Senlis, , France

Strasbourg, , France

Strasbourg, , France

Strasbourg, , France

Suresnes, , France

Vandœuvre-lès-Nancy, , France

Verdun, , France

Aachen, , Germany

Aachen, , Germany

Aschaffenburg, , Germany

Augsburg, , Germany

Bergisch Gladbach, , Germany

Berlin, , Germany

Berlin, , Germany

Berlin, , Germany

Berlin, , Germany

Berlin, , Germany

Bietigheim, , Germany

Bochum, , Germany

Bochum, , Germany

Bonn, , Germany

Bremen, , Germany

Chemnitz, , Germany

Cologne, , Germany

Cologne, , Germany

Cologne, , Germany

Darmstadt, , Germany

Dessau, , Germany

Dortmund, , Germany

Dresden, , Germany

Dresden, , Germany

Duisburg, , Germany

Erlangen, , Germany

Eschweiler, , Germany

Essen, , Germany

Esslingen am Neckar, , Germany

Flensburg, , Germany

Frankfurt, , Germany

Frechen, , Germany

Fulda, , Germany

Geilenkirchen, , Germany

Gifhorn, , Germany

Greifswald, , Germany

Gummersbach, , Germany

Halle, , Germany

Hamburg, , Germany

Hamburg, , Germany

Hamburg, , Germany

Hamburg, , Germany

Hanover, , Germany

Hanover, , Germany

Heidelberg, , Germany

Heidenheim, , Germany

Hildesheim, , Germany

Hof, , Germany

Homburg/Saar, , Germany

Kassel, , Germany

Kassel, , Germany

Köthen, , Germany

Kronach, , Germany

Laatzen, , Germany

Leer, , Germany

Lehrte, , Germany

Leipzig, , Germany

Lemgo, , Germany

Leverkusen, , Germany

Limburg, , Germany

Ludwigsburg, , Germany

Lübeck, , Germany

Magdeburg, , Germany

Magdeburg, , Germany

Magedburg, , Germany

Mainz, , Germany

Mannheim, , Germany

Marburg, , Germany

Marktredwitz, , Germany

Marl, , Germany

Moers, , Germany

Mönchengladbach, , Germany

Mutlangen, , Germany

Mülheim, , Germany

München, , Germany

Münster, , Germany

Neunkirchen/Saar, , Germany

Neustadt, , Germany

Nordhausen, , Germany

Oldenburg, , Germany

Olpe, , Germany

Pinneberg, , Germany

Regensburg, , Germany

Regensburg, , Germany

Remscheid, , Germany

Rostock, , Germany

Rostock, , Germany

Rotenburg (Wümme), , Germany

Rötha, , Germany

Schönebeck, , Germany

Schwerin, , Germany

Stade, , Germany

Stuttgart, , Germany

Suhl, , Germany

Troisdorf, , Germany

Ulm, , Germany

Velbert, , Germany

Wernigerode, , Germany

Wiesbaden, , Germany

Würselen, , Germany

Amersfoort, , Netherlands

Capelle aan den IJssel, , Netherlands

Leiden, , Netherlands

Tilburg, , Netherlands

Ålesund, , Norway

Bergen, , Norway

Kristiansand, , Norway

Lorenskog, , Norway

Oslo, , Norway

Aveiro, , Portugal

Coimbra, , Portugal

Lisbon, , Portugal

Porto, , Portugal

Porto, , Portugal

Dammam, , Saudi Arabia

Jeddah, , Saudi Arabia

Jeddah, , Saudi Arabia

Riyadh, , Saudi Arabia

Alicante, Alicante, Spain

Elche, Alicante, Spain

Elda, Alicante, Spain

Torrevieja, Alicante, Spain

Palma de Mallorca, Balearic Islands, Spain

Barcelona, Barcelona, Spain

Barcelona, Barcelona, Spain

Barcelona, Barcelona, Spain

Barcelona, Barcelona, Spain

Barcelona, Barcelona, Spain

Barcelona, Barcelona, Spain

Manresa, Barcelona, Spain

Sabadell, Barcelona, Spain

Sant Cugat del Vallès, Barcelona, Spain

Burgos, Burgos, Spain

Cadiz, Cadiz, Spain

Santander, Cantabria, Spain

Castellon, Castellon, Spain

Córdoba, Cordoba, Spain

Girona, Girona, Spain

Granada, Granada, Spain

Donostia / San Sebastian, Guipuzcoa, Spain

Huelva, Huelva, Spain

A Coruña, La Coruña, Spain

Lleida, Lerida, Spain

Alcorcón, Madrid, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Parla, Madrid, Spain

Murcia, Murcia, Spain

Navarra, Navarre, Spain

Oviedo, Principality of Asturias, Spain

Seville, Sevilla, Spain

Reus, Tarragona, Spain

Sagunto, Valencia, Spain

Valencia, Valencia, Spain

Valencia, Valencia, Spain

Valencia, Valencia, Spain

Valencia, Valencia, Spain

Bilbao, Vizcaya, Spain

Zaragoza, Zaragoza, Spain

Lund, , Sweden

Uppsala, , Sweden

Vaxjo, , Sweden

Aarau, , Switzerland

Basel, , Switzerland

Bern, , Switzerland

Chur, , Switzerland

Lucerne, , Switzerland

Winterthur, , Switzerland

Zurich, , Switzerland

Zurich, , Switzerland

Zurich, , Switzerland

Countries

Austria; Belgium; Czechia; Denmark; Estonia; Finland; France; Germany; Netherlands; Norway; Portugal; Saudi Arabia; Spain; Sweden; Switzerland

References

Li Y, Hu M, Zhang Z, Chu M, Xu R, Liu L, Dong W, Yang M, Zhang R. Cost-effectiveness analysis of continuing bevacizumab plus chemotherapy versus chemotherapy alone after first progression of metastatic colorectal cancer. Cancer Med. 2024 Jan;13(1):e6904. doi: 10.1002/cam4.6904. Epub 2024 Jan 8.

Reference Type: DERIVED

PMID: 38186268 (View on PubMed)

Kubicka S, Greil R, Andre T, Bennouna J, Sastre J, Van Cutsem E, von Moos R, Osterlund P, Reyes-Rivera I, Muller T, Makrutzki M, Arnold D; ML18147 study investigators including AIO, GERCOR, FFCD, UNICANCER GI, TTD, BGDO, GEMCAD, and AGMT groups. Bevacizumab plus chemotherapy continued beyond first progression in patients with metastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings. Ann Oncol. 2013 Sep;24(9):2342-9. doi: 10.1093/annonc/mdt231. Epub 2013 Jul 12.

Reference Type: DERIVED

PMID: 23852309 (View on PubMed)

Bennouna J, Sastre J, Arnold D, Osterlund P, Greil R, Van Cutsem E, von Moos R, Vieitez JM, Bouche O, Borg C, Steffens CC, Alonso-Orduna V, Schlichting C, Reyes-Rivera I, Bendahmane B, Andre T, Kubicka S; ML18147 Study Investigators. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013 Jan;14(1):29-37. doi: 10.1016/S1470-2045(12)70477-1. Epub 2012 Nov 16.

Reference Type: DERIVED

PMID: 23168366 (View on PubMed)

Other Identifiers

2006-004634-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ML18147

Identifier Type: -

Identifier Source: org_study_id