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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

September 8, 2005
June 13, 2014
May 2004
December 2006   (final data collection date for 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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 under 5-FU/FA plus irinotecan with or without cetuximab
Complete list of historical versions of study NCT00154102 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]
    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).
  • 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 ] [ Designated as safety issue: No ]
    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).
  • 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 ] [ Designated as safety issue: No ]
    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).
  • 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 ] [ Designated as safety issue: No ]
    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).
  • 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 ] [ Designated as safety issue: No ]

    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.

  • 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 ] [ Designated as safety issue: No ]
    Participants with no residual tumor after on-study surgery for metastases
  • 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 ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: Yes ]
    Please refer to Adverse Events section for further details
  • Overall Survival time
  • Response Rate and Disease Control rate
  • Duration or Response
  • Quality of Life
  • Safety
Not Provided
Not Provided
 
Cetuximab Combined With Irinotecan in First-line Therapy for Metastatic Colorectal Cancer (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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Epidermal Growth Factor Receptor (EGFR) Expressing Metastatic Colorectal Cancer
  • Drug: 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
  • 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
  • Experimental: Cetuximab Plus FOLFIRI
    Interventions:
    • Drug: Cetuximab
    • Drug: FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)
  • Active Comparator: FOLFIRI Alone
    Intervention: Drug: FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1221
March 2011
December 2006   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Chile,   Czech Republic,   Finland,   France,   Germany,   Greece,   Hong Kong,   Hungary,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Romania,   Russian Federation,   Singapore,   Slovakia,   South Africa,   Spain,   Sweden,   Taiwan,   Turkey,   Ukraine,   United Kingdom
 
NCT00154102
EMR 62202-013
Yes
Monika Foerster, Merck Serono
Merck KGaA
Not Provided
Principal Investigator: Eric van Cutsem, Professor University Hospital Gasthuisberg, Department Internal Medicine, Leuven, Belgium
Merck KGaA
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP