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

This study has been completed.
Sponsor:
Information provided by:
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00154102
First received: September 8, 2005
Last updated: June 13, 2014
Last verified: June 2014
Results First Received: November 30, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Epidermal Growth Factor Receptor (EGFR) Expressing Metastatic Colorectal Cancer
Interventions: Drug: Cetuximab
Drug: FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

First/Last subject in: 10 Aug 2004/4 Nov 2005. Clinical cut-off efficacy analyses except survival: 27 Jul 2006, Cut off date IRC data: 14 Dec 2006; cut-off safety analyses: 30 Nov 2007; cut-off survival analyses: 31 May 2009; cut-off KRAS analyses: 28 Aug 2009.

1221 subjects were randomised or treated, of whom 1198 were randomised and treated.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

At the prescreening visit the subject completed the first informed consent form, and a sample of tumor tissue for determination of EGFR expression was to be obtained.

The screening (baseline) visit was performed no more than 21 days before randomization. EGFR-expressing subjects completed a second informed consent form to participate in the study.


Reporting Groups
  Description
Cetuximab Plus FOLFIRI Cetuximab intravenous infusion of 400mg/m^2 for the first infusion then weekly intravenous infusion of 250mg/m^2. 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 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

Participant Flow:   Overall Study
    Cetuximab Plus FOLFIRI     FOLFIRI Alone  
STARTED     599 [1]   599 [2]
COMPLETED     592     597  
NOT COMPLETED     7     2  
investigational study phase ongoing                 7                 2  
[1] Randomized and treated subjects; 1 additional subject was treated but not randomised
[2] Randomized and treated subjects; 3 additional subjects were treated but not randomised



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Cetuximab Plus FOLFIRI Cetuximab intravenous infusion of 400mg/m^2 for the first infusion then weekly intravenous infusion of 250mg/m^2. 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 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
Total Total of all reporting groups

Baseline Measures
    Cetuximab Plus FOLFIRI     FOLFIRI Alone     Total  
Number of Participants  
[units: participants]
  599     599     1198  
Age [1]
[units: years]
Mean ± Standard Deviation
  60.0  ± 10.52     59.8  ± 11.06     59.9  ± 10.79  
Age, Customized [1]
[units: participants]
     
Missing     1     0     1  
Between 18 and 65 years     374     377     751  
>=65 years     224     222     446  
Gender  
[units: participants]
     
Female     230     243     473  
Male     369     356     725  
Region of Enrollment  
[units: participants]
     
Western Europe     262     267     529  
Eastern Europe     203     201     404  
Rest of the World     134     131     265  
[1] Age missing for 1 subject



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Primary:   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 ]

3.  Primary:   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 ]

4.  Secondary:   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 ]

5.  Secondary:   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 ]

6.  Secondary:   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 ]

7.  Secondary:   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 ]

8.  Secondary:   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 ]

9.  Secondary:   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 ]

10.  Secondary:   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 ]

11.  Secondary:   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 ]

12.  Secondary:   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 ]

13.  Secondary:   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 ]

14.  Secondary:   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 ]

15.  Secondary:   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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
A non-specific outcome measure 'Safety' was deleted from the entry in error. A replacement outcome was created. The outcome refers to adverse events.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Monika Foerster/Clinical Trial Leader
Organization: Merck Serono
phone: +496151729517
e-mail: monika.foerster@merck.de


Publications of Results:
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
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

Publications automatically indexed to this study:

Responsible Party: Monika Foerster, Merck Serono
ClinicalTrials.gov Identifier: NCT00154102     History of Changes
Other Study ID Numbers: EMR 62202-013
Study First Received: September 8, 2005
Results First Received: November 30, 2010
Last Updated: June 13, 2014
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP