Single Nucleotide Polymorphism(SNP)Study. ICORG 08-40, V4

Correlation of Single Nucleotide Polymorphism (SNP) Profile of Domain III of EGFR to Skin Toxicity and Disease Response to Treatment With Erbitux Requirements

Primary Objective:

Correlation of the skin and/or eye toxicity grade secondary to Cetuximab or Panitumumab and the SNP profile of the Epidermal Growth Factor Receptor (EGFR) domain III region.

Secondary Objectives:

Correlation of SNP profile with indicators of tumour response parameters, such as radiological response, duration of response, time to progression (TTP), overall survival (OS) time, incidence of non-dermatological adverse events.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer; Non-Small Cell Lung Cancer

Detailed Description

Baseline assessment:

• Contact Lenses
• Medical History
• Previous chemotherapy
• Vital Signs (weight, height, Karnofsky Performance status, heart rate, blood pressure)
• Symptom Assessment (Pre-existing skin and/or eye conditions, CEA measurement (CRC only), Disease status (TNM Staging))
• Planned chemotherapy regimen
• Radiotherapy

Blood Sample: A 2ml blood sample should be collected in ethylenediamine-tetraacetic acid (EDTA) containing Vacutainer at any time before or after starting treatment. DNA will be extracted from the samples and the 11 SNPs in the region of the EGFR gene encoding domain III will be characterized.

Follow-up Assessment: with every second cycle of Cetuximab- or Panitumumab-containing regimen (CRC: every 2. Week; NSCLC: every 3-4 weeks):

• Visit Number and Date
• Vital Signs (weight, height, Karnofsky Performance status, heart rate, blood pressure)
• Symptom Assessment (CEA measurement (CRC only), Disease status (TMN Staging), Skin Toxicity (CTCAE) grading)
• Current chemotherapy regimen
• Radiotherapy
• CEA measurement only for CRC (every second cycle/every 4 weeks)

Long-term follow-up (up to 5 years):

• CT restaging (TNM Staging) should be done 3 monthly for as long as the subject is receiving Cetuximab- or Panitumumab- containing regimen or if there is suspicion of disease progression.
• OS

• Study Type: Observational
• Enrollment (Actual): 161

Contacts and Locations

Study Locations

• Ireland
  • Cork, Ireland
    • Bon Secours Hospital
  • Cork, Ireland
    • Cork University Hospital
  • Dublin, Ireland
    • Beaumont Hospital
  • Dublin, Ireland, 7
    • Mater Misericordiae University Hospital
  • Dublin, Ireland, 4
    • St Vincent's University Hospital
  • Dublin, Ireland
    • The Adelaide & Meath Hosptal, Dublin Incorporating The National Children's Hospital
  • Galway, Ireland
    • Galway University Hospital
  • Louth, Ireland
    • Our Lady of Lourdes Hospital, Drogheda
  • Waterford, Ireland
    • Waterford Regional Hospital
  • Donegal
    • Letterkenny, Donegal, Ireland
      • Letterkenny General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patient Population:

150 Patients with histologically proven stage IV (AJCC 7th Edition) colorectal cancer (CRC) expressing wild-type KRAS or stage IV non-small cell lung cancer (NSCLC) expressing EGFR (tested by immunohistochemistry (IHC)), with no previous exposure to Cetuximab or Panitumumab, who will receive treatment with an EGFR-antibody (Cetuximab or Panitumumab).

Description

Inclusion Criteria:

1. Stage IV (AJCC 7th Edition TMN Staging, Appendix C), histologically confirmed CRC with wild-type KRAS and not a candidate for metastasectomy.
2. Stage IV (AJCC 7th Edition, TMN Staging, Appendix C) NSCLC expressing EGFR (IHC tested)
3. Patients, who will receive treatment with an EGFR-antibody (Cetuximab or Panitumumab).
4. Karnofsky performance status (Appendix B) score ≥60.

5. Acceptable laboratory values:

   • Haemoglobin ≥ 9 g/dL.
   • Neutrophil count ≥ 1.0 x 10^9/L.
   • Platelet count ≥100 x 10^9/L.
   • Serum creatinine ≤1.5 times the upper limit of normal.
   • Bilirubin ≤1.5 times the upper limit of normal.
   • Aspartate aminotransferase and alanine aminotransferase ≤5 times the upper limit of normal.

Exclusion Criteria:

1. Aged < 18 years
2. Prior exposure to Cetuximab or Panitumumab
3. The CRC does not carry wild-type KRAS.
4. The NSCLC stains negative for EGFR protein expression
5. Second cancer diagnosis (apart from non-melanoma skin cancer)
6. Known hypersensitivity to Cetuximab or Panitumumab, or murine protein.
7. Known history of coronary artery disease, arrhythmias, or congestive heart failure (If the treating physician feels that a patient's coronary artery disease / arrhythmia / congestive heart failure does not place him/her at risk from treatment with an anti-EGFR antibody, the person can be included. This is a clinical decision, which has to be made by the treating physician).
8. Known to be pregnant (pregnancy test is not mandatory) or breast-feeding.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Stage IV CRC
Stage IV NSCLC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between the type and degree of reported skin and/or eye reaction and the SNP profile of the EGFR domain III region.	Using Common Terminology Criteria for Adverse Events (CTCAE) version 4	Throughout treatment with up to 5 years in follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between the SNP profile(s) and disease response	Time to progression TTP and OS over 5 years	Throughout treatment with up to 5 years in follow up

Collaborators and Investigators

• Sponsor: Cancer Trials Ireland

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2011
• Primary Completion (Actual): May 11, 2021
• Study Completion (Actual): May 11, 2021

Study Registration Dates

• First Submitted: November 9, 2012
• First Submitted That Met QC Criteria: November 9, 2012
• First Posted (Estimated): November 14, 2012

Study Record Updates

• Last Update Posted (Actual): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 4, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: ICORG 08-40