Clinical trial NCT00700102: A Study of Avastin (Bevacizumab) Plus Crossover Fluoropyrimidine-Based Chemotherapy in Patients With Metastatic Colorectal Cancer.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2008-06-18
Enrollment: 820
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall Survival: Time From Randomization to Death From Any Cause
timeFrame: within 6.5 years
Secondary outcomes:
measure: Overall Survival: Months From Time of First Line Therapy
timeFrame: within approximately 9.6 years
measure: Participants With Progression Free Survival Event
timeFrame: within 6.5 years
measure: Progression Free Survival: Time to Event
timeFrame: within 6.5 years
measure: Response Rate: Percentage of Participants With Best Overall Response, Defined as Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST Criteria
timeFrame: within 6.5 years
measure: Response Rate: Participants With Response Status Based on RECIST Criteria
timeFrame: within 6.5 years
Other outcomes:
Locations:
city: Dornbirn
country: Austria
city: Fürstenfeld
country: Austria
city: Graz
country: Austria
city: Graz
country: Austria
city: Hall in Tirol
country: Austria
city: Innsbruck
country: Austria
city: Krems
country: Austria
city: Leoben
country: Austria
city: Linz
country: Austria
city: Rankweil
country: Austria
city: Ried-innkreis
country: Austria
city: Salzburg
country: Austria
city: St Pölten
country: Austria
city: St Veit An Der Glan
country: Austria
city: Steyr
country: Austria
city: Villach
country: Austria
city: Waidhofen A D Thaya
country: Austria
city: Wels
country: Austria
city: Wiener Neustadt
country: Austria
city: Wien
country: Austria
city: Aalst
country: Belgium
city: Assebroek
country: Belgium
city: La Louviere
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Turnhout
country: Belgium
city: Brno
country: Czech Republic
city: Olomouc
country: Czech Republic
city: Praha 5
country: Czech Republic
city: Praha
country: Czech Republic
city: Esbjerg
country: Denmark
city: Herlev
country: Denmark
city: Herning
country: Denmark
city: Hillerod
country: Denmark
city: København
country: Denmark
city: Naestved
country: Denmark
city: Tallinn
country: Estonia
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Helsinki
country: Finland
city: Oulu
country: Finland
city: Tampere
country: Finland
city: Turku
country: Finland
city: Vaasa
country: Finland
city: Agen
country: France
city: Albi
country: France
city: Amiens
country: France
city: Amilly
country: France
city: Antibes
country: France
city: Antony
country: France
city: Arras
country: France
city: Avignon
country: France
city: Besancon
country: France
city: Beziers
country: France
city: Bordeaux
country: France
city: Bordeaux
country: France
city: Bourgoin Jallieu
country: France
city: Caen
country: France
city: Cahors
country: France
city: Chambray Les Tours
country: France
city: Clermont-ferrand
country: France
city: Colmar
country: France
city: Compiegne
country: France
city: Dechy
country: France
city: Dijon
country: France
city: Grenoble
country: France
city: La Roche Sur Yon
country: France
city: La Seyne Sur Mer
country: France
city: Lagny Sur Marne
country: France
city: Le Kremlin Bicetre
country: France
city: Le Mans
country: France
city: Libourne
country: France
city: Lille
country: France
city: Lille
country: France
city: Limoges
country: France
city: Lliie
country: France
city: Longjumeau
country: France
city: Lyon
country: France
city: Lyon
country: France
city: Lyon
country: France
city: Macon
country: France
city: Marseille
country: France
city: Marseille
country: France
city: Marseille
country: France
city: Meaux
country: France
city: Metz
country: France
city: Mont De Marsan
country: France
city: Montbeliard
country: France
city: Montfermeil
country: France
city: Montpellier
country: France
city: Mougins
country: France
city: Nancy
country: France
city: Nantes
country: France
city: Nantes
country: France
city: Neuilly Sur Seine
country: France
city: Nevers
country: France
city: Nice
country: France
city: Orleans
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Perigueux
country: France
city: Pessac
country: France
city: Pierre Benite
country: France
city: Pontoise
country: France
city: Reims CEDEX
country: France
city: Reims
country: France
city: Rennes
country: France
city: Rodez
country: France
city: Rouen
country: France
city: Saint Gregoire
country: France
city: Saint Herblain
country: France
city: Saint Nazaire
country: France
city: Senlis
country: France
city: St Brieuc
country: France
city: St Cloud
country: France
city: Strasbourg
country: France
city: Strasbourg
country: France
city: Strasbourg
country: France
city: Suresnes
country: France
city: Vandoeuvre Les Nancy
country: France
city: Vandoeuvre-les-nancy
country: France
city: Verdun
country: France
city: Aachen
country: Germany
city: Aachen
country: Germany
city: Aschaffenburg
country: Germany
city: Augsburg
country: Germany
city: Bergisch Gladbach
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Bietigheim
country: Germany
city: Bochum
country: Germany
city: Bochum
country: Germany
city: Bonn
country: Germany
city: Bremen
country: Germany
city: Chemnitz
country: Germany
city: Darmstadt
country: Germany
city: Dessau-Roßlau
country: Germany
city: Dortmund
country: Germany
city: Dresden
country: Germany
city: Dresden
country: Germany
city: Duisburg
country: Germany
city: Erlangen
country: Germany
city: Eschweiler
country: Germany
city: Essen
country: Germany
city: Esslingen
country: Germany
city: Flensburg
country: Germany
city: Frankfurt
country: Germany
city: Frechen
country: Germany
city: Fulda
country: Germany
city: Geilenkirchen
country: Germany
city: Gifhorn
country: Germany
city: Greifswald
country: Germany
city: Gummersbach
country: Germany
city: Halle
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Heidenheim
country: Germany
city: Hildesheim
country: Germany
city: Hof
country: Germany
city: Homburg/Saar
country: Germany
city: Kassel
country: Germany
city: Kassel
country: Germany
city: Kronach
country: Germany
city: Köln
country: Germany
city: Köln
country: Germany
city: Köln
country: Germany
city: Köthen
country: Germany
city: Laatzen
country: Germany
city: Leer
country: Germany
city: Lehrte
country: Germany
city: Leipzig
country: Germany
city: Lemgo
country: Germany
city: Leverkusen
country: Germany
city: Limburg
country: Germany
city: Ludwigsburg
country: Germany
city: Lübeck
country: Germany
city: Magdeburg
country: Germany
city: Magdeburg
country: Germany
city: Magedburg
country: Germany
city: Mainz
country: Germany
city: Mannheim
country: Germany
city: Marburg
country: Germany
city: Marktredwitz
country: Germany
city: Marl
country: Germany
city: Moers
country: Germany
city: Muenchen
country: Germany
city: Muenster
country: Germany
city: Mutlangen
country: Germany
city: Mönchengladbach
country: Germany
city: Mülheim
country: Germany
city: Neunkirchen/Saar
country: Germany
city: Neustadt
country: Germany
city: Nordhausen
country: Germany
city: Oldenburg
country: Germany
city: Olpe
country: Germany
city: Pinneberg
country: Germany
city: Regensburg
country: Germany
city: Regensburg
country: Germany
city: Remscheid
country: Germany
city: Rostock
country: Germany
city: Rostock
country: Germany
city: Rotenburg
country: Germany
city: Rötha
country: Germany
city: Schwerin
country: Germany
city: Schönebeck
country: Germany
city: Stade
country: Germany
city: Stuttgart
country: Germany
city: Suhl
country: Germany
city: Troisdorf
country: Germany
city: Ulm
country: Germany
city: Velbert
country: Germany
city: Wernigerode
country: Germany
city: Wiesbaden
country: Germany
city: Wuerselen
country: Germany
city: Amersfoort
country: Netherlands
city: Capelle a/d IJssel
country: Netherlands
city: Leiden
country: Netherlands
city: Tilburg
country: Netherlands
city: Bergen
country: Norway
city: Kristiansand
country: Norway
city: Lorenskog
country: Norway
city: Oslo
country: Norway
city: Ålesund
country: Norway
city: Aveiro
country: Portugal
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Porto
country: Portugal
city: Dammam
country: Saudi Arabia
city: Jeddah
country: Saudi Arabia
city: Jeddah
country: Saudi Arabia
city: Riyadh
country: Saudi Arabia
city: Elche
country: Spain
state: Alicante
city: Elda
country: Spain
state: Alicante
city: Torrevieja
country: Spain
state: Alicante
city: Oviedo
country: Spain
state: Asturias
city: Manresa
country: Spain
state: Barcelona
city: Sabadell
country: Spain
state: Barcelona
city: Sant Cugat Del Valles
country: Spain
state: Barcelona
city: Cádiz
country: Spain
state: Cadiz
city: Santander
country: Spain
state: Cantabria
city: San Sebastian
country: Spain
state: Guipuzcoa
city: Palma de Mallorca
country: Spain
state: Islas Baleares
city: Alcorcon
country: Spain
state: Madrid
city: Parla
country: Spain
state: Madrid
city: Reus
country: Spain
state: Tarragona
city: Sagunto
country: Spain
state: Valencia
city: Bilbao
country: Spain
state: Vizcaya
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Burgos
country: Spain
city: Castellon
country: Spain
city: Cordoba
country: Spain
city: Girona
country: Spain
city: Granada
country: Spain
city: Huelva
country: Spain
city: La Coruña
country: Spain
city: Lerida
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Murcia
country: Spain
city: Navarra
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Lund
country: Sweden
city: Uppsala
country: Sweden
city: Vaxjo
country: Sweden
city: Aarau
country: Switzerland
city: Basel
country: Switzerland
city: Bern
country: Switzerland
city: Chur
country: Switzerland
city: Luzern
country: Switzerland
city: Winterthur
country: Switzerland
city: Zürich
country: Switzerland
city: Zürich
country: Switzerland
city: Zürich
country: Switzerland
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.