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

Phase 3

Completed

Conditions: Epidermal Growth Factor Receptor (EGFR) Expressing Metastatic Colorectal Cancer

Interventions: Drug: Cetuximab
Drug: FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)

Registration Number: NCT00154102

Lead Sponsor: Merck KGaA, Darmstadt, Germany

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1221

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cetuximab Plus FOLFIRI	FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)	-
Cetuximab Plus FOLFIRI	Cetuximab	-
FOLFIRI Alone	FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)	-

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) Time - Independent Review Committee (IRC) Assessments	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 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 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.

Secondary Outcome Measures

Name	Time	Method
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	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 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	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	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	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).
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	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 (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	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	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	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	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	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 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	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 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	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	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	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	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	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 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	Please refer to Adverse Events section for further details