A Study of Avastin (Bevacizumab) Plus Crossover Fluoropyrimidine-Based Chemotherapy in Patients With Metastatic Colorectal Cancer.
A Randomized, Open-label Phase III Intergroup Study: Effect of Adding Bevacizumab to Cross Over Fluoropyrimidine Based Chemotherapy (CTx) in Patients With Metastatic Colorectal Cancer and Disease Progression Under First-line Standard CTx/Bevacizumab Combination
2 other identifiers
interventional
820
14 countries
297
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 colorectal-cancer
Started Feb 2006
Typical duration for phase_3 colorectal-cancer
297 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2006
CompletedFirst Submitted
Initial submission to the registry
June 17, 2008
CompletedFirst Posted
Study publicly available on registry
June 18, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2013
CompletedResults Posted
Study results publicly available
July 30, 2015
CompletedJuly 30, 2015
July 1, 2015
7.2 years
June 17, 2008
July 2, 2015
July 2, 2015
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Survival: Time From Randomization to Death From Any Cause
within 6.5 years
Secondary Outcomes (5)
Overall Survival: Months From Time of First Line Therapy
within approximately 9.6 years
Participants With Progression Free Survival Event
within 6.5 years
Progression Free Survival: Time to Event
within 6.5 years
Response Rate: Percentage of Participants With Best Overall Response, Defined as Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST Criteria
within 6.5 years
Response Rate: Participants With Response Status Based on RECIST Criteria
within 6.5 years
Study Arms (2)
Chemotherapy
ACTIVE COMPARATORChemotherapy alone until disease progression, unacceptable toxicity, or patient refusal
Chemotherapy + Bevacizumab
EXPERIMENTALChemotherapy and Bevacizumab until disease progression, unacceptable toxicity, or patient refusal
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (300)
Unknown Facility
Dornbirn, 6850, Austria
Unknown Facility
Fürstenfeld, 8280, Austria
Unknown Facility
Graz, 8020, Austria
Unknown Facility
Graz, 8036, Austria
Unknown Facility
Hall in Tirol, 6060, Austria
Unknown Facility
Innsbruck, 6020, Austria
Unknown Facility
Krems, 3500, Austria
Unknown Facility
Leoben, 8700, Austria
Unknown Facility
Linz, 4020, Austria
Unknown Facility
Rankweil, 6830, Austria
Unknown Facility
Ried-innkreis, 4910, Austria
Unknown Facility
Salzburg, 5020, Austria
Unknown Facility
Sankt Pölten, 3100, Austria
Unknown Facility
Sankt Veit an der Glan, 9300, Austria
Unknown Facility
Steyr, 4400, Austria
Unknown Facility
Vienna, 1160, Austria
Unknown Facility
Villach, 9500, Austria
Unknown Facility
Waidhofen A D Thaya, 3830, Austria
Unknown Facility
Wels, 4600, Austria
Unknown Facility
Wiener Neustadt, 2700, Austria
Unknown Facility
Aalst, 9300, Belgium
Unknown Facility
Assebroek, 8310, Belgium
Unknown Facility
La Louvière, 7100, Belgium
Unknown Facility
Leuven, 3000, Belgium
Unknown Facility
Liège, 4000, Belgium
Unknown Facility
Turnhout, 2300, Belgium
Unknown Facility
Brno, 656 53, Czechia
Unknown Facility
Olomouc, 775 20, Czechia
Unknown Facility
Prague, 150 06, Czechia
Unknown Facility
Prague, 180 81, Czechia
Unknown Facility
Copenhagen, 2100, Denmark
Unknown Facility
Esbjerg, 6700, Denmark
Unknown Facility
Herlev, 2730, Denmark
Unknown Facility
Herning, 7400, Denmark
Unknown Facility
Hillerød, 3400, Denmark
Unknown Facility
Næstved, 4700, Denmark
Unknown Facility
Tallinn, 11312, Estonia
Unknown Facility
Tallinn, 13419, Estonia
Unknown Facility
Tartu, 51014, Estonia
Unknown Facility
Helsinki, 00029, Finland
Unknown Facility
Oulu, 90029, Finland
Unknown Facility
Tampere, 33520, Finland
Unknown Facility
Turku, 20520, Finland
Unknown Facility
Vaasa, 65130, Finland
Unknown Facility
Agen, 47000, France
Unknown Facility
Albi, 81030, France
Unknown Facility
Amiens, 80090, France
Unknown Facility
Amilly, 45200, France
Unknown Facility
Antibes, 06600, France
Unknown Facility
Antony, 92166, France
Unknown Facility
Arras, 62000, France
Unknown Facility
Avignon, 84918, France
Unknown Facility
Besançon, 25030, France
Unknown Facility
Béziers, 34525, France
Unknown Facility
Bordeaux, 33075, France
Unknown Facility
Bordeaux, 33077, France
Unknown Facility
Bourgoin, 38317, France
Unknown Facility
Caen, 14033, France
Unknown Facility
Cahors, 46005, France
Unknown Facility
Chambray-lès-Tours, 37171, France
Unknown Facility
Clermont-Ferrand, 63003, France
Unknown Facility
Colmar, 68024, France
Unknown Facility
Compiègne, 60321, France
Unknown Facility
Dechy, 59187, France
Unknown Facility
Dijon, 21079, France
Unknown Facility
Grenoble, 38000, France
Unknown Facility
La Roche-sur-Yon, 85925, France
Unknown Facility
La Seyne-sur-Mer, 83500, France
Unknown Facility
Lagny-sur-Marne, 77405, France
Unknown Facility
Le Kremlin-Bicêtre, 94275, France
Unknown Facility
Le Mans, 72037, France
Unknown Facility
Libourne, 33505, France
Unknown Facility
Lille, 59020, France
Unknown Facility
Lille, 59037, France
Unknown Facility
Limoges, 87042, France
Unknown Facility
Lliie, 59003, France
Unknown Facility
Longjumeau, 91161, France
Unknown Facility
Lyon, 69317, France
Unknown Facility
Lyon, 69337, France
Unknown Facility
Lyon, 69373, France
Unknown Facility
Marseille, 13273, France
Unknown Facility
Marseille, 13274, France
Unknown Facility
Marseille, 13285, France
Unknown Facility
Mâcon, 71000, France
Unknown Facility
Meaux, 77104, France
Unknown Facility
Metz, 57038, France
Unknown Facility
Mont-de-Marsan, 40024, France
Unknown Facility
Montbéliard, 25209, France
Unknown Facility
Montfermeil, 93370, France
Unknown Facility
Montpellier, 34298, France
Unknown Facility
Mougins, 6250, France
Unknown Facility
Nancy, 54100, France
Unknown Facility
Nantes, 44093, France
Unknown Facility
Nantes, 44202, France
Unknown Facility
Neuilly-sur-Seine, 92200, France
Unknown Facility
Nevers, 58033, France
Unknown Facility
Nice, 06189, France
Unknown Facility
Orléans, 45100, France
Unknown Facility
Paris, 75571, France
Unknown Facility
Paris, 75651, France
Unknown Facility
Paris, 75674, France
Unknown Facility
Paris, 75877, France
Unknown Facility
Paris, 75908, France
Unknown Facility
Paris, 75970, France
Unknown Facility
Pessac, 33604, France
Unknown Facility
Périgueux, 24000, France
Unknown Facility
Pierre-Bénite, 69495, France
Unknown Facility
Pontoise, 95300, France
Unknown Facility
Reims, 51056, France
Unknown Facility
Reims, 51092, France
Unknown Facility
Rennes, 35033, France
Unknown Facility
Rodez, 12027, France
Unknown Facility
Rouen, 76031, France
Unknown Facility
Saint-Brieuc, 22027, France
Unknown Facility
Saint-Cloud, 92210, France
Unknown Facility
Saint-Grégoire, 35768, France
Unknown Facility
Saint-Herblain, 44805, France
Unknown Facility
Saint-Nazaire, 44600, France
Unknown Facility
Senlis, 60309, France
Unknown Facility
Strasbourg, 67010, France
Unknown Facility
Strasbourg, 67065, France
Unknown Facility
Strasbourg, 67098, France
Unknown Facility
Suresnes, 92151, France
Unknown Facility
Vandœuvre-lès-Nancy, 54511, France
Unknown Facility
Verdun, 55107, France
Unknown Facility
Aachen, 52064, Germany
Unknown Facility
Aachen, 52074, Germany
Unknown Facility
Aschaffenburg, 63739, Germany
Unknown Facility
Augsburg, 86150, Germany
Unknown Facility
Bergisch Gladbach, 51429, Germany
Unknown Facility
Berlin, 10117, Germany
Unknown Facility
Berlin, 10707, Germany
Unknown Facility
Berlin, 13125, Germany
Unknown Facility
Berlin, 13585, Germany
Unknown Facility
Berlin, 14195, Germany
Unknown Facility
Bietigheim, 74321, Germany
Unknown Facility
Bochum, 44791, Germany
Unknown Facility
Bochum, 44892, Germany
Unknown Facility
Bonn, 53113, Germany
Unknown Facility
Bremen, 28325, Germany
Unknown Facility
Chemnitz, 09119, Germany
Unknown Facility
Cologne, 50677, Germany
Unknown Facility
Cologne, 50924, Germany
Unknown Facility
Cologne, 51103, Germany
Unknown Facility
Darmstadt, 64295, Germany
Unknown Facility
Dessau, 06847, Germany
Unknown Facility
Dortmund, 44137, Germany
Unknown Facility
Dresden, 01127, Germany
Unknown Facility
Dresden, 01307, Germany
Unknown Facility
Duisburg, 47166, Germany
Unknown Facility
Erlangen, 97054, Germany
Unknown Facility
Eschweiler, 52249, Germany
Unknown Facility
Essen, 45122, Germany
Unknown Facility
Esslingen am Neckar, 73730, Germany
Unknown Facility
Flensburg, 24939, Germany
Unknown Facility
Frankfurt, 60596, Germany
Unknown Facility
Frechen, 50226, Germany
Unknown Facility
Fulda, 36043, Germany
Unknown Facility
Geilenkirchen, 52511, Germany
Unknown Facility
Gifhorn, 38518, Germany
Unknown Facility
Greifswald, 17475, Germany
Unknown Facility
Gummersbach, 51643, Germany
Unknown Facility
Halle, 06120, Germany
Unknown Facility
Hamburg, 20249, Germany
Unknown Facility
Hamburg, 22087, Germany
Unknown Facility
Hamburg, 22457, Germany
Unknown Facility
Hamburg, 22767, Germany
Unknown Facility
Hanover, 30449, Germany
Unknown Facility
Hanover, 30625, Germany
Unknown Facility
Heidelberg, 69120, Germany
Unknown Facility
Heidenheim, 89522, Germany
Unknown Facility
Hildesheim, 31135, Germany
Unknown Facility
Hof, 95028, Germany
Unknown Facility
Homburg/Saar, 66424, Germany
Unknown Facility
Kassel, 34119, Germany
Unknown Facility
Kassel, 34131, Germany
Unknown Facility
Köthen, 06366, Germany
Unknown Facility
Kronach, 96317, Germany
Unknown Facility
Laatzen, 30880, Germany
Unknown Facility
Leer, 26789, Germany
Unknown Facility
Lehrte, 31275, Germany
Unknown Facility
Leipzig, 04289, Germany
Unknown Facility
Lemgo, 32657, Germany
Unknown Facility
Leverkusen, 51375, Germany
Unknown Facility
Limburg, 65549, Germany
Unknown Facility
Ludwigsburg, 71640, Germany
Unknown Facility
Lübeck, 23562, Germany
Unknown Facility
Magdeburg, 39120, Germany
Unknown Facility
Magdeburg, 39130, Germany
Unknown Facility
Magedburg, 39104, Germany
Unknown Facility
Mainz, 55131, Germany
Unknown Facility
Mannheim, 68165, Germany
Unknown Facility
Marburg, 35043, Germany
Unknown Facility
Marktredwitz, 95615, Germany
Unknown Facility
Marl, 45768, Germany
Unknown Facility
Moers, 47441, Germany
Unknown Facility
Mönchengladbach, 41063, Germany
Unknown Facility
Mutlangen, 73557, Germany
Unknown Facility
Mülheim, 45468, Germany
Unknown Facility
München, 81377, Germany
Unknown Facility
Münster, 48149, Germany
Unknown Facility
Neunkirchen/Saar, 66538, Germany
Unknown Facility
Neustadt, 01844, Germany
Unknown Facility
Nordhausen, 99734, Germany
Unknown Facility
Oldenburg, 26133, Germany
Unknown Facility
Olpe, 57462, Germany
Unknown Facility
Pinneberg, 25421, Germany
Unknown Facility
Regensburg, 93049, Germany
Unknown Facility
Regensburg, 93053, Germany
Unknown Facility
Remscheid, 42859, Germany
Unknown Facility
Rostock, 18055, Germany
Unknown Facility
Rostock, 18107, Germany
Unknown Facility
Rotenburg (Wümme), 27356, Germany
Unknown Facility
Rötha, 04571, Germany
Unknown Facility
Schönebeck, 39218, Germany
Unknown Facility
Schwerin, 19057, Germany
Unknown Facility
Stade, 21680, Germany
Unknown Facility
Stuttgart, 70174, Germany
Unknown Facility
Suhl, 98527, Germany
Unknown Facility
Troisdorf, 53840, Germany
Unknown Facility
Ulm, 89081, Germany
Unknown Facility
Velbert, 42551, Germany
Unknown Facility
Wernigerode, 38855, Germany
Unknown Facility
Wiesbaden, 65199, Germany
Unknown Facility
Würselen, 52146, Germany
Unknown Facility
Amersfoort, 3818 ES, Netherlands
Unknown Facility
Capelle aan den IJssel, NL 2900 AR, Netherlands
Unknown Facility
Leiden, 2334 CK, Netherlands
Unknown Facility
Tilburg, 5042 AD, Netherlands
Unknown Facility
Ålesund, 6026, Norway
Unknown Facility
Bergen, 5021, Norway
Unknown Facility
Kristiansand, 4604, Norway
Unknown Facility
Lorenskog, 1478, Norway
Unknown Facility
Oslo, 0407, Norway
Unknown Facility
Aveiro, 3814-501, Portugal
Unknown Facility
Coimbra, 3000-075, Portugal
Unknown Facility
Lisbon, 1495-005, Portugal
Unknown Facility
Porto, 4200-072, Portugal
Unknown Facility
Porto, 4200-319, Portugal
Unknown Facility
Dammam, 31444, Saudi Arabia
Unknown Facility
Jeddah, 21497, Saudi Arabia
Unknown Facility
Jeddah, 21589, Saudi Arabia
Unknown Facility
Riyadh, 11211, Saudi Arabia
Unknown Facility
Alicante, Alicante, 3010, Spain
Unknown Facility
Elche, Alicante, 03203, Spain
Unknown Facility
Elda, Alicante, 03600, Spain
Unknown Facility
Torrevieja, Alicante, 03186, Spain
Unknown Facility
Palma de Mallorca, Balearic Islands, 07198, Spain
Unknown Facility
Barcelona, Barcelona, 08017, Spain
Unknown Facility
Barcelona, Barcelona, 08035, Spain
Unknown Facility
Barcelona, Barcelona, 08041, Spain
Unknown Facility
Barcelona, Barcelona, 08227, Spain
Unknown Facility
Barcelona, Barcelona, 08906, Spain
Unknown Facility
Barcelona, Barcelona, 08916, Spain
Unknown Facility
Manresa, Barcelona, 08243, Spain
Unknown Facility
Sabadell, Barcelona, 08208, Spain
Unknown Facility
Sant Cugat del Vallès, Barcelona, 28981, Spain
Unknown Facility
Burgos, Burgos, 09006, Spain
Unknown Facility
Cadiz, Cadiz, 11009, Spain
Unknown Facility
Santander, Cantabria, 39008, Spain
Unknown Facility
Castellon, Castellon, 12002, Spain
Unknown Facility
Córdoba, Cordoba, 14004, Spain
Unknown Facility
Girona, Girona, 17007, Spain
Unknown Facility
Granada, Granada, 18014, Spain
Unknown Facility
Donostia / San Sebastian, Guipuzcoa, 20080, Spain
Unknown Facility
Huelva, Huelva, 21005, Spain
Unknown Facility
A Coruña, La Coruña, 15006, Spain
Unknown Facility
Lleida, Lerida, 25198, Spain
Unknown Facility
Alcorcón, Madrid, 28922, Spain
Unknown Facility
Madrid, Madrid, 28002, Spain
Unknown Facility
Madrid, Madrid, 28007, Spain
Unknown Facility
Madrid, Madrid, 28034, Spain
Unknown Facility
Madrid, Madrid, 28040, Spain
Unknown Facility
Madrid, Madrid, 28041, Spain
Unknown Facility
Madrid, Madrid, 28943, Spain
Unknown Facility
Parla, Madrid, 28981, Spain
Unknown Facility
Murcia, Murcia, 30008, Spain
Unknown Facility
Navarra, Navarre, 31008, Spain
Unknown Facility
Oviedo, Principality of Asturias, 33011, Spain
Unknown Facility
Seville, Sevilla, 41014, Spain
Unknown Facility
Reus, Tarragona, 43204, Spain
Unknown Facility
Sagunto, Valencia, 46520, Spain
Unknown Facility
Valencia, Valencia, 41014, Spain
Unknown Facility
Valencia, Valencia, 46015, Spain
Unknown Facility
Valencia, Valencia, 46017, Spain
Unknown Facility
Valencia, Valencia, 46026, Spain
Unknown Facility
Bilbao, Vizcaya, 48013, Spain
Unknown Facility
Zaragoza, Zaragoza, 50009, Spain
Unknown Facility
Lund, 22185, Sweden
Unknown Facility
Uppsala, 75185, Sweden
Unknown Facility
Vaxjo, 35185, Sweden
Unknown Facility
Aarau, 5000, Switzerland
Unknown Facility
Basel, 4031, Switzerland
Unknown Facility
Bern, 3011, Switzerland
Unknown Facility
Chur, 7000, Switzerland
Unknown Facility
Lucerne, 6004, Switzerland
Unknown Facility
Winterthur, 8401, Switzerland
Unknown Facility
Zurich, 8038, Switzerland
Unknown Facility
Zurich, 8063, Switzerland
Unknown Facility
Zurich, 8091, Switzerland
Related Publications (3)
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.
PMID: 38186268DERIVEDKubicka 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.
PMID: 23852309DERIVEDBennouna 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.
PMID: 23168366DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Patients in the study who were randomized to receive bevacizumab could continue to receive bevacizumab following discontinuation of chemotherapy, thereby minimizing any potential bias introduced by differential follow-up time in the treatment arms.
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 17, 2008
First Posted
June 18, 2008
Study Start
February 1, 2006
Primary Completion
May 1, 2013
Study Completion
May 1, 2013
Last Updated
July 30, 2015
Results First Posted
July 30, 2015
Record last verified: 2015-07