Clinical trial NCT01726309: Single Nucleotide Polymorphism(SNP)Study. ICORG 08-40, V4
Official title: Correlation of Single Nucleotide Polymorphism (SNP) Profile of Domain III of EGFR to Skin Toxicity and Disease Response to Treatment With Erbitux Requirements
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Colorectal Cancer
Non-Small Cell Lung Cancer
Lead sponsor: Cancer Trials Ireland
Sponsor class: NETWORK
First posted: 2012-11-14
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Correlation between the type and degree of reported skin and/or eye reaction and the SNP profile of the EGFR domain III region.
timeFrame: Throughout treatment with up to 5 years in follow up
Secondary outcomes:
measure: Correlation between the SNP profile(s) and disease response
timeFrame: Throughout treatment with up to 5 years in follow up
Other outcomes:
Locations:
city: Letterkenny
country: Ireland
facility: Letterkenny General Hospital
state: Donegal
city: Cork
country: Ireland
facility: Bon Secours Hospital
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: St Vincent's University Hospital
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: The Adelaide & Meath Hosptal, Dublin Incorporating The National Children's Hospital
city: Galway
country: Ireland
facility: Galway University Hospital
city: Louth
country: Ireland
facility: Our Lady of Lourdes Hospital, Drogheda
city: Waterford
country: Ireland
facility: Waterford Regional Hospital
Study officials:
References: