Cetuximab Combined With Irinotecan in First-line Therapy for Metastatic Colorectal Cancer (CRYSTAL)
CRYSTAL
Open, Randomized, Controlled, Multicenter Phase III Study Comparing 5FU/ FA Plus Irinotecan Plus Cetuximab Versus 5FU/FA Plus Irinotecan as First-line Treatment for Epidermal Growth Factor Receptor-expressing Metastatic Colorectal Cancer
1 other identifier
interventional
1,221
29 countries
146
Brief Summary
Drugs used against cancer work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Giving combination chemotherapy together with cetuximab as first treatment after diagnosis of a metastatic colorectal cancer ('1st-line' treatment) may improve the treatment efficacy. However, it is not yet known whether giving combination chemotherapy together with cetuximab is more effective than combination chemotherapy alone. This open-label trial investigates the effectiveness of cetuximab in combination with a standard and effective chemotherapy (5-Fluorouracil (5FU)/Folinic acid (FA) plus irinotecan) for metastatic colorectal cancer in first-line setting, compared to the same chemotherapy alone on patient expressing the epidermal growth factor (EGF) receptor. Patients expressing this EGF Receptor will be randomly assign in one of the 2 groups to either receive the combination chemotherapy alone or with cetuximab (open-label study) and will then be treated until progression of the disease or unacceptable toxicity occur. Regular efficacy assessments (every 8 weeks) based on imaging will be performed throughout the study together with regular safety assessments (e.g. safety labs). An independent Safety Board of experts will also monitor safety data. After participant discontinuation from the trial, regular updates on further treatments and survival status will be requested from the investigator. The entire study (from the first patient entering the study to the last collect of follow-up information) is 4-5 years long.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started May 2004
Longer than P75 for phase_3
146 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
May 1, 2004
CompletedFirst Submitted
Initial submission to the registry
September 8, 2005
CompletedFirst Posted
Study publicly available on registry
September 12, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2006
CompletedResults Posted
Study results publicly available
February 23, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2011
CompletedJanuary 30, 2017
January 1, 2017
2.6 years
September 8, 2005
November 30, 2010
January 12, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Progression-free Survival (PFS) Time - Independent Review Committee (IRC) Assessments
Duration from randomization until radiological progression (based on modified World Health Organisation (WHO) criteria) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.
Time from randomisation to disease progression, death or last tumour assessment, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Progression-free Survival Time (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population) - Independent Review Committee (IRC) Assessments
Duration from randomization until radiological progression (based on modified WHO criteria) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.
Time from randomisation to disease progression, death or last tumour assessment, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Progression-free Survival Time (KRAS Mutant Population) - Independent Review Committee (IRC) Assessments
Duration from randomization until radiological progression (based on modified WHO criteria) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.
Time from randomisation to disease progression, death or last tumour assessment, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Secondary Outcomes (12)
Overall Survival Time (OS)
Time from randomisation to death or last day known to be alive, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 31 May 2009
Overall Survival Time (KRAS Wild-Type Population)
Time from randomisation to death or last day known to be alive reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 31 May 2009
Overall Survival Time (KRAS Mutant Population)
Time from randomisation to death or last day known to be alive reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 31 May 2009
Best Overall Response Rate - Independent Review Committee (IRC) Assessments
evaluations were performed every 6 weeks until progression reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Best Overall Response Rate (KRAS Wild-Type Population) - Independent Review Committee (IRC) Assessments
evaluations were performed every 6 weeks until progression reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
- +7 more secondary outcomes
Study Arms (2)
Cetuximab Plus FOLFIRI
EXPERIMENTALFOLFIRI Alone
ACTIVE COMPARATORInterventions
Cetuximab intravenous infusion of 400mg/m\^2 for the first infusion then weekly intravenous infusion of 250mg/m\^2. Number of Cycles: until progression or unacceptable toxicity develops
Bi-weekly Irinotecan infusion of 180mg/m\^2, Folinic Acid infusion of 400mg/m\^2 (racemic) or 200mg/m\^2 (L-form), 5-Fluorouracil bolus of 400mg/m\^2 followed by a 46-hour continuous infusion of 2400mg/m\^2 Number of Cycles: until progression or unacceptable toxicity develops
Eligibility Criteria
You may qualify if:
- Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
- Inoperable metastatic disease
- Immunohistochemical evidence of epidermal growth factor receptor expression in tumor tissue
- Presence of at least 1 bi-dimensionally measurable index lesion
You may not qualify if:
- Previous irinotecan-based chemotherapy
- Previous chemotherapy for colorectal cancer except adjuvant treatment if terminated more than 6 months before the start of study treatment
- Radiotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before the start of study treatment
- Brain metastasis
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (154)
Research Site
Buenos Aires, Argentina
Research Site
Bedford Park, Australia
Research Site
Darlinghurst, Australia
Research Site
Heidelberg, Australia
Research Site
Nedlands, Australia
Research Site
West Perth, Australia
Research Site
Woodville, Australia
Research Site
Innsbruck, Austria
Research Site
Klagenfurt, Austria
Research Site
Kufstein, Austria
Research Site
Salzburg, Austria
Research Site
Sankt Pölten, Austria
Research Site
Sankt Veit an der Glan, Austria
Research Site
Vienna, Austria
Research Site
Wels, Austria
Research Site
Antwerp, Belgium
Research Site
Bonheiden, Belgium
Research Site
Brussels, Belgium
Research Site
Edegem, Belgium
Research Site
Ghent, Belgium
Research Site
Leuven, Belgium
Research Site
Liège, Belgium
Research Site
Goiânia, Brazil
Research Site
Porto Alegre, Brazil
Research Site
Santo André, Brazil
Research Site
São Paulo, Brazil
Research Site
Pleven, Bulgaria
Research Site
Plovidiv, Bulgaria
Research Site
Sofia, Bulgaria
Research Site
Varna, Bulgaria
Research Site
Santiago-Las Condes, Chile
Research Site
Santiago-Providencia, Chile
Research Site
Chomutov, Czechia
Research Site
Prague, Czechia
Research Site
Turku, Finland
Research Site
Bordeaux, France
Research Site
Boulogne-Billancourt, France
Research Site
Colmar, France
Research Site
Grenoble, France
Research Site
La Roche-sur-Yon, France
Research Site
Lorient, France
Research Site
Marseille, France
Research Sites
Nantes, France
Research Site
Périgueux, France
Research Site
Rennes, France
Research Site
Saint-Grégoire, France
Research Site
Strasbourg, France
Research Site
Toulon, France
Research Site
Villejuif, France
Research Site
Dortmund, Germany
Research Site
Dresden, Germany
Research Site
Düsseldorf, Germany
Research Site
Essen, Germany
Research Site
Frankfurt am Main, Germany
Research Site
Freiburg im Breisgau, Germany
Research Site
Göttingen, Germany
Research Site
Halle, Germany
Research Site
Hamburg, Germany
Research Site
Heidelberg, Germany
Research Site
Homburg/Saar, Germany
Research Site
Jena, Germany
Research Site
Mainz, Germany
Research Site
Mannheim, Germany
Research Site
München, Germany
Research Site
Oldenburg, Germany
Research Site
Ulm, Germany
Research Site
Alexandroupoli, Greece
Research Site
Athens, Greece
Research Site
Heraklion, Greece
Research Site
Pokfulam, Hong Kong
Research Site
Shatin, Hong Kong
Research Site
Budapest, Hungary
Research Site
Debrecen, Hungary
Research Site
Győr, Hungary
Research Site
Kecskemét, Hungary
Research Site
Pécs, Hungary
Research Site
Ancona, Italy
Research Site
Aviano, Italy
Research Site
Bari, Italy
Research Site
Benevento, Italy
Research Site
Florence, Italy
Research Site
Mantova, Italy
Research Site
Milan, Italy
Research Site
Modena, Italy
Research Site
Napoli, Italy
Research Site
Reggio Emilia, Italy
Research Site
Roma, Italy
Research Site
Rozzano, Italy
Research Site
México, Mexico
Research Site
Amsterdam, Netherlands
Research Site
Apeldoom, Netherlands
Research Site
Blaricum, Netherlands
Research Site
Roosendaal, Netherlands
Research Site
The Hague, Netherlands
Research Site
Zwolle, Netherlands
Research Site
Bialystok, Poland
Research Site
Gliwice, Poland
Research Site
Krakow, Poland
Research Site
Opole, Poland
Research Site
Poznan, Poland
Research Site
Warsaw, Poland
Research Site
Wroclaw, Poland
Research Site
Cluj-Napoca, Romania
Research Site
Iași, Romania
Research Site
Suceava, Romania
Research Site
Moscow, Russia
Research Site
Saint Petersburg, Russia
Research Site
Yaroslavl, Russia
Research Site
Singapore, Singapore
Research Site
Banská Bystrica, Slovakia
Research Site
Bratislava, Slovakia
Research Site
Košice, Slovakia
Research Site
Trnava, Slovakia
Research Site
Žilina, Slovakia
Research Site
Cape Town, South Africa
Research Site
Durban, South Africa
Research Site
Johannesburg, South Africa
Research Site
Port Elizabeth, South Africa
Research Site
Pretoria, South Africa
Research Site
Seoul, South Korea
Research Site
A Coruña, Spain
Research Site
Barcelona, Spain
Research Site
Cadiz, Spain
Research Site
Madrid, Spain
Research Site
Palma de Mallorca, Spain
Research Site
Valencia, Spain
Research Site
Gothenburg, Sweden
Research Site
Stockholm, Sweden
Research Site
Changhua, Taiwan
Research Site
Chiayi City, Taiwan
Research Site
Taipei, Taiwan
Research Site
Taoyuan District, Taiwan
Research Site
Ankara, Turkey (Türkiye)
Research Site
Istanbul, Turkey (Türkiye)
Research Site
Izmir, Turkey (Türkiye)
Research Site
Charkassy, Ukraine
Research Site
Donetsk, Ukraine
Research Site
Ivano-Frankivsk, Ukraine
Research Site
Kiev, Ukraine
Research Site
Kryvyi Rih, Ukraine
Research Site
Luhansk, Ukraine
Research Site
Lviv, Ukraine
Research Site
Uzhhorod, Ukraine
Research Site
Zhaporozhye, Ukraine
Research Site
Brighton, United Kingdom
Research Site
Cambridge, United Kingdom
Research Site
Glasgow, United Kingdom
Research Site
Guildford, United Kingdom
Research Site
Kent, United Kingdom
Research Site
Leicester, United Kingdom
Research Site
London, United Kingdom
Research Site
Peterborough, United Kingdom
Research Site
Rhyl, United Kingdom
Research Site
Sutton, United Kingdom
Related Publications (6)
Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pinter T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. doi: 10.1056/NEJMoa0805019.
PMID: 19339720RESULTVan Cutsem E, Lang I, Folprecht G, Nowacki M, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Celik I, Kohne C Cetuximab plus FOLFIRI in the treatment of metastatic colorectal cancer (mCRC): The influence of KRAS and BRAF biomarkers on outcome: Updated data from the CRYSTAL trial. ASCO 2010 Gastrointestinal Cancers Symposium, Orlando, USA January 2010 Abstract No: 281
RESULTLang I, Kohne CH, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Zubel A, Van Cutsem E Cetuximab plus FOLFIRI in 1st-line treatment of metastatic colorectal cancer: Quality of life (QoL) analysis of patients (pts) with KRAS wild-type (wt) tumours in the CRYSTAL trial. European Journal of Cancer Supplements. 2009 7(2):345
RESULTDercle L, Lu L, Lichtenstein P, Yang H, Wang D, Zhu J, Wu F, Piessevaux H, Schwartz LH, Zhao B. Impact of Variability in Portal Venous Phase Acquisition Timing in Tumor Density Measurement and Treatment Response Assessment: Metastatic Colorectal Cancer as a Paradigm. JCO Clin Cancer Inform. 2017 Nov;1:1-8. doi: 10.1200/CCI.17.00108.
PMID: 30657405DERIVEDTejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, Esser R, Lenz HJ, Heinemann V. Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. JAMA Oncol. 2017 Feb 1;3(2):194-201. doi: 10.1001/jamaoncol.2016.3797.
PMID: 27722750DERIVEDLicitra L, Storkel S, Kerr KM, Van Cutsem E, Pirker R, Hirsch FR, Vermorken JB, von Heydebreck A, Esser R, Celik I, Ciardiello F. Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer. 2013 Apr;49(6):1161-8. doi: 10.1016/j.ejca.2012.11.018. Epub 2012 Dec 19.
PMID: 23265711DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
A non-specific outcome measure 'Safety' was deleted from the entry in error. A replacement outcome was created. The outcome refers to adverse events.
Results Point of Contact
- Title
- Monika Foerster/Clinical Trial Leader
- Organization
- Merck Serono
Study Officials
- PRINCIPAL INVESTIGATOR
Eric van Cutsem, Professor
University Hospital Gasthuisberg, Department Internal Medicine, Leuven, Belgium
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
Study Record Dates
First Submitted
September 8, 2005
First Posted
September 12, 2005
Study Start
May 1, 2004
Primary Completion
December 1, 2006
Study Completion
March 1, 2011
Last Updated
January 30, 2017
Results First Posted
February 23, 2011
Record last verified: 2017-01