Cetuximab Combined With Irinotecan in First-line Therapy for Metastatic Colorectal Cancer (CRYSTAL)

NCT ID: NCT00154102

Last Updated: 2017-01-30

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1221 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-05-31

Study Completion Date

2011-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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Epidermal Growth Factor Receptor (EGFR) Expressing Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cetuximab Plus FOLFIRI

Group Type EXPERIMENTAL

Cetuximab

Intervention Type DRUG

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)

Intervention Type 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

FOLFIRI Alone

Group Type ACTIVE_COMPARATOR

FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)

Intervention Type 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

Interventions

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Cetuximab

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

Intervention Type DRUG

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role lead

Responsible Party

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Merck Serono

Principal Investigators

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Eric van Cutsem, Professor

Role: PRINCIPAL_INVESTIGATOR

University Hospital Gasthuisberg, Department Internal Medicine, Leuven, Belgium

Locations

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Research Site

Buenos Aires, , Argentina

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Bedford Park, , Australia

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Darlinghurst, , Australia

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Heidelberg, , Australia

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Nedlands, , Australia

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West Perth, , Australia

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Woodville, , Australia

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Innsbruck, , Austria

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Klagenfurt, , Austria

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Kufstein, , Austria

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Salzburg, , Austria

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Sankt Pölten, , Austria

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Sankt Veit an der Glan, , Austria

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Vienna, , Austria

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Wels, , Austria

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Antwerp, , Belgium

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Bonheiden, , Belgium

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Brussels, , Belgium

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Edegem, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Goiânia, , Brazil

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Porto Alegre, , Brazil

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Santo André, , Brazil

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São Paulo, , Brazil

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Pleven, , Bulgaria

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Plovidiv, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Santiago-Las Condes, , Chile

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Santiago-Providencia, , Chile

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Chomutov, , Czechia

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Prague, , Czechia

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Turku, , Finland

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Bordeaux, , France

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Boulogne-Billancourt, , France

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Colmar, , France

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Grenoble, , France

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La Roche-sur-Yon, , France

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Lorient, , France

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Marseille, , France

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Nantes, , France

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Périgueux, , France

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Rennes, , France

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Saint-Grégoire, , France

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Strasbourg, , France

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Toulon, , France

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Villejuif, , France

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Dortmund, , Germany

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Dresden, , Germany

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Düsseldorf, , Germany

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Essen, , Germany

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Frankfurt am Main, , Germany

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Freiburg im Breisgau, , Germany

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Göttingen, , Germany

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Halle, , Germany

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Hamburg, , Germany

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Heidelberg, , Germany

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Homburg/Saar, , Germany

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Jena, , Germany

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Mainz, , Germany

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Mannheim, , Germany

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München, , Germany

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Oldenburg, , Germany

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Ulm, , Germany

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Alexandroupoli, , Greece

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Athens, , Greece

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Heraklion, , Greece

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Pokfulam, , Hong Kong

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Shatin, , Hong Kong

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Budapest, , Hungary

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Debrecen, , Hungary

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Győr, , Hungary

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Kecskemét, , Hungary

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Pécs, , Hungary

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Ancona, , Italy

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Aviano, , Italy

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Bari, , Italy

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Benevento, , Italy

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Florence, , Italy

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Mantova, , Italy

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Milan, , Italy

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Modena, , Italy

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Napoli, , Italy

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Reggio Emilia, , Italy

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Roma, , Italy

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Rozzano, , Italy

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México, , Mexico

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Amsterdam, , Netherlands

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Apeldoom, , Netherlands

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Blaricum, , Netherlands

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Roosendaal, , Netherlands

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The Hague, , Netherlands

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Zwolle, , Netherlands

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Bialystok, , Poland

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Gliwice, , Poland

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Krakow, , Poland

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Opole, , Poland

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Poznan, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Cluj-Napoca, , Romania

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Iași, , Romania

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Suceava, , Romania

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Moscow, , Russia

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Saint Petersburg, , Russia

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Yaroslavl, , Russia

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Singapore, , Singapore

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Banská Bystrica, , Slovakia

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Bratislava, , Slovakia

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Košice, , Slovakia

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Trnava, , Slovakia

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Žilina, , Slovakia

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Cape Town, , South Africa

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Durban, , South Africa

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Johannesburg, , South Africa

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Port Elizabeth, , South Africa

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Pretoria, , South Africa

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Seoul, , South Korea

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A Coruña, , Spain

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Barcelona, , Spain

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Cadiz, , Spain

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Madrid, , Spain

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Palma de Mallorca, , Spain

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Valencia, , Spain

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Gothenburg, , Sweden

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Stockholm, , Sweden

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Changhua, , Taiwan

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Chiayi City, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Charkassy, , Ukraine

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Donetsk, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kiev, , Ukraine

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Kryvyi Rih, , Ukraine

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Luhansk, , Ukraine

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Lviv, , Ukraine

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Uzhhorod, , Ukraine

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Zhaporozhye, , Ukraine

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Brighton, , United Kingdom

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Cambridge, , United Kingdom

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Glasgow, , United Kingdom

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Guildford, , United Kingdom

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Kent, , United Kingdom

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Leicester, , United Kingdom

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London, , United Kingdom

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Peterborough, , United Kingdom

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Rhyl, , United Kingdom

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Sutton, , United Kingdom

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Countries

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Argentina Australia Austria Belgium Brazil Bulgaria Chile Czechia Finland France Germany Greece Hong Kong Hungary Italy Mexico Netherlands Poland Romania Russia Singapore Slovakia South Africa South Korea Spain Sweden Taiwan Turkey (Türkiye) Ukraine United Kingdom

References

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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.

Reference Type RESULT
PMID: 19339720 (View on PubMed)

Van 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

Reference Type RESULT

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

Reference Type RESULT

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.

Reference Type DERIVED
PMID: 30657405 (View on PubMed)

Tejpar 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.

Reference Type DERIVED
PMID: 27722750 (View on PubMed)

Licitra 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.

Reference Type DERIVED
PMID: 23265711 (View on PubMed)

Other Identifiers

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EMR 62202-013

Identifier Type: -

Identifier Source: org_study_id

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