Epidermal Growth Factor Receptor (EGFR) Expressing Metastatic Colorectal CancerPhase 3CRYSTALNCT00154102
Cetuximab Combined With Irinotecan in First-line Therapy for Metastatic Colorectal Cancer (CRYSTAL)
A Phase 3 study testing Cetuximab and FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan) in people with Epidermal Growth Factor Receptor (EGFR) Expressing Metastatic Colorectal Cancer, run by Merck KGaA, Darmstadt, Germany at 154 sites in 30 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epidermal Growth Factor Receptor (EGFR) Expressing Metastatic Colorectal Cancer
- What is being tested?
- Cetuximab and FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,221 participants
- Where
- 154 sitesin 30 countries
- Study dates
- May 2004to Mar 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
154 sites in 30 countries.
154 sites in 30 countries
Germany17 sites
Research Site
Dortmund
Research Site
Dresden
Research Site
Düsseldorf
Research Site
Essen
Research Site
Frankfurt am Main
Research Site
Freiburg im Breisgau
Research Site
Göttingen
Research Site
Halle
Research Site
Hamburg
Research Site
Heidelberg
Research Site
Homburg/Saar
Research Site
Jena
Research Site
Mainz
Research Site
Mannheim
Research Site
München
Research Site
Oldenburg
Research Site
Ulm
France14 sites
Research Site
Bordeaux
Research Site
Boulogne-Billancourt
Research Site
Colmar
Research Site
Grenoble
Research Site
La Roche-sur-Yon
Research Site
Lorient
Research Site
Marseille
Research Sites
Nantes
Research Site
Périgueux
Research Site
Rennes
Research Site
Saint-Grégoire
Research Site
Strasbourg
Research Site
Toulon
Research Site
Villejuif
Italy12 sites
Research Site
Ancona
Research Site
Aviano
Research Site
Bari
Research Site
Benevento
Research Site
Florence
Research Site
Mantua
Research Site
Milan
Research Site
Modena
Research Site
Naples
Research Site
Reggio Emilia
Research Site
Roma
Research Site
Rozzano
United Kingdom10 sites
Research Site
Brighton
Research Site
Cambridge
Research Site
Glasgow
Research Site
Guildford
Research Site
Kent
Research Site
Leicester
Research Site
London
Research Site
Peterborough
Research Site
Rhyl
Research Site
Sutton
Ukraine9 sites
Research Site
Charkassy
Research Site
Donetsk
Research Site
Ivano-Frankivsk
Research Site
Kiev
Research Site
Kryvyi Rih
Research Site
Luhansk
Research Site
Lviv
Research Site
Uzhhorod
Research Site
Zhaporozhye
Austria8 sites
Research Site
Innsbruck
Research Site
Klagenfurt
Research Site
Kufstein
Research Site
Salzburg
Research Site
Sankt Pölten
Research Site
Sankt Veit an der Glan
Research Site
Vienna
Research Site
Wels
Belgium7 sites
Research Site
Antwerp
Research Site
Bonheiden
Research Site
Brussels
Research Site
Edegem
Research Site
Ghent
Research Site
Leuven
Research Site
Liège
Poland7 sites
Research Site
Bialystok
Research Site
Gliwice
Research Site
Krakow
Research Site
Opole
Research Site
Poznan
Research Site
Warsaw
Research Site
Wroclaw
Australia6 sites
Research Site
Bedford Park
Research Site
Darlinghurst
Research Site
Heidelberg
Research Site
Nedlands
Research Site
West Perth
Research Site
Woodville
Netherlands6 sites
Research Site
Amsterdam
Research Site
Apeldoom
Research Site
Blaricum
Research Site
Roosendaal
Research Site
The Hague
Research Site
Zwolle
Spain6 sites
Research Site
A Coruña
Research Site
Barcelona
Research Site
Cadiz
Research Site
Madrid
Research Site
Palma de Mallorca
Research Site
Valencia
Hungary5 sites
Research Site
Budapest
Research Site
Debrecen
Research Site
Győr
Research Site
Kecskemét
Research Site
Pécs
Slovakia5 sites
Research Site
Banská Bystrica
Research Site
Bratislava
Research Site
Košice
Research Site
Trnava
Research Site
Žilina
South Africa5 sites
Research Site
Cape Town
Research Site
Durban
Research Site
Johannesburg
Research Site
Port Elizabeth
Research Site
Pretoria
Brazil4 sites
Research Site
Goiânia
Research Site
Porto Alegre
Research Site
Santo André
Research Site
São Paulo
Bulgaria4 sites
Research Site
Pleven
Research Site
Plovidiv
Research Site
Sofia
Research Site
Varna
Taiwan4 sites
Research Site
Changhua
Research Site
Chiayi City
Research Site
Taipei
Research Site
Taoyuan
Greece3 sites
Research Site
Alexandroupoli
Research Site
Athens
Research Site
Heraklion
Romania3 sites
Research Site
Cluj-Napoca
Research Site
Iași
Research Site
Suceava
Russia3 sites
Research Site
Moscow
Research Site
Saint Petersburg
Research Site
Yaroslavl
Turkey (Türkiye)3 sites
Research Site
Ankara
Research Site
Istanbul
Research Site
Izmir
Chile2 sites
Research Site
Santiago-Las Condes
Research Site
Santiago-Providencia
About this study
Official title: 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
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.
Read more
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.
- Being tested
- Cetuximab, FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)
- Keywords
- Metastatic colorectal cancer, EGFR, Irinotecan, cetuximab, first-line treatment
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
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
FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)Drug
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
| Study group | Role | What they receive |
|---|---|---|
| Cetuximab Plus FOLFIRI | Experimental | Not described Receives: Drug: Cetuximab; Drug: FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan) |
| FOLFIRI Alone | Active comparator | Not described Receives: Drug: FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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 randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is later.
Measured: 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 randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is later.
Measured: 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 randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is later.
Measured: 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
The best overall response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as the best overall response according to radiological assessments (based on modified WHO criteria).
Measured: 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
The best overall response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as the best overall response according to radiological assessments (based on modified WHO criteria).
Measured: 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 Mutant Population) - Independent Review Committee (IRC) Assessments
The best overall response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as the best overall response according to radiological assessments (based on modified WHO criteria).
Measured: 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
Disease Control Rate - Independent Review Committee (IRC) Assessments
The disease control rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response + Stable Disease as best overall response according to radiological assessments (based on modified WHO criteria).
Measured: 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
Duration of Response - Independent Review Committee (IRC) Assessments
Time from first assessment of Complete Response or Partial Response to disease progression or death (within 60 days of last tumor assessment).
Patients without event are censored on the date of last tumor assessment. Tumor assessments based on modified WHO criteria.
Measured: Time from first assessment of complete response or partial response to disease progression, death or last tumor assessment reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Participants With No Residual Tumor After Metastatic Surgery
Participants with no residual tumor after on-study surgery for metastases
Measured: time from first dose up to 30 days after last dose of study treatment reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 30 Nov 2007
Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status
Mean global health status scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a better QoL.
Measured: at baseline, at week 8, at week 16, at week 24, at week 32, and at week 40, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Quality of Life Assessment (EORTC QLQ-C30) Social Functioning
Mean social functioning scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a higher level of functioning.
Measured: at baseline, at week 8, at week 16, at week 24, at week 32, and at week 40, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Safety - Number of Patients Experiencing Any Adverse Event
Please refer to Adverse Events section for further details
Measured: time from first dose up to 30 days after last dose of study treatment reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 30 Nov 2007
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startMay 2004
- Primary completionDec 2006
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Epidermal Growth Factor Receptor (EGFR) Expressing Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,221 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Eric van Cutsem, Professor, Principal investigator, University Hospital Gasthuisberg, Department Internal Medicine, Leuven, Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00154102
- Sponsor's protocol ID
- EMR 62202-013
- Acronym
- CRYSTAL
- Status last verified
- Jan 2017
- First submitted
- 8 Sep 2005
- Last updated
- 30 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 19339720Van 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
Lang 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
Dercle 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.
PubMed 30657405Tejpar 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.
PubMed 27722750Licitra 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.
PubMed 23265711
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00154102
- Acronym / sponsor ID
- CRYSTAL / EMR 62202-013
- Keywords
- Metastatic colorectal cancer, EGFR, Irinotecan, cetuximab, first-line treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,221 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- May 2004
- Primary completion
- Dec 2006 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 12 Sep 2005 (estimated)
- Results
- Posted 23 Feb 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cetuximab Plus FOLFIRI | Experimental | Drug: Cetuximab, Drug: FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan) |
| FOLFIRI Alone | Active comparator | Drug: FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CetuximabCetuximab 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 | Drug | Cetuximab Plus FOLFIRI |
| FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)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 | Drug | Cetuximab Plus FOLFIRI, FOLFIRI Alone |
Primary outcome
Progression-free Survival (PFS) Time - Independent Review Committee (IRC) Assessments
Time frame: 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
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.
Progression-free Survival Time (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population) - Independent Review Committee (IRC) Assessments
Time frame: 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
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.
Progression-free Survival Time (KRAS Mutant Population) - Independent Review Committee (IRC) Assessments
Time frame: 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
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.
12 secondary outcomes
Overall Survival Time (OS)
Time frame: 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 frame: 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 frame: 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
Time frame: 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
Time frame: 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 Mutant Population) - Independent Review Committee (IRC) Assessments
Time frame: 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
Disease Control Rate - Independent Review Committee (IRC) Assessments
Time frame: 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
Duration of Response - Independent Review Committee (IRC) Assessments
Time frame: Time from first assessment of complete response or partial response to disease progression, death or last tumor assessment reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Participants With No Residual Tumor After Metastatic Surgery
Time frame: time from first dose up to 30 days after last dose of study treatment reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 30 Nov 2007
Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status
Time frame: at baseline, at week 8, at week 16, at week 24, at week 32, and at week 40, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Quality of Life Assessment (EORTC QLQ-C30) Social Functioning
Time frame: at baseline, at week 8, at week 16, at week 24, at week 32, and at week 40, reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 27 July 2006
Safety - Number of Patients Experiencing Any Adverse Event
Time frame: time from first dose up to 30 days after last dose of study treatment reported between day of first patient randomised, 10 Aug 2004, until cut-off date, 30 Nov 2007
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19339720Van 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.
- Results publicationVan 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
- Results publicationLang 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
- Derived from this study: PubMed 30657405Dercle 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.
- Derived from this study: PubMed 27722750Tejpar 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.
- Derived from this study: PubMed 23265711Licitra 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric van Cutsem, Professor principal investigator
University Hospital Gasthuisberg, Department Internal Medicine, Leuven, Belgium
154 sites in 30 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cetuximab and FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan) in people with Epidermal Growth Factor Receptor (EGFR) Expressing Metastatic Colorectal Cancer, run by Merck KGaA, Darmstadt, Germany at 154 sites in 30 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 154 sites in Germany, France, Italy, United Kingdom, Ukraine and 25 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Feb 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) Time - Independent Review Committee (IRC) Assessments (time frame: 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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00154102, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2017; AzTrials last refreshed its copy on 7 Nov 2026.