None listed
Conditions
Brief summary
This study aims to determine whether patients with a high level of Amphiregulin/epiregulin (AREG/EREG) cancer cell markers for advanced stage colorectal cancer have a better treatment response to a combined chemo- and biological regime. Who is it for? You may be eligible for this study if you are aged 18 years or older, you have been diagnosed with right-sided RAS/BRAF wild type advanced stage colorectal cancer that has not been responsive to an initial treatment regime and you have previously provided a tumour sample for testing. Study details All participants who meet the inclusion criteria will firstly have their previously collected tumour sample tested to determine the level of AREG/EREG cancer cell markers present. Participants who have a high level of AREG and/or EREG cell markers will then begin a treatment regime that combines chemotherapy- irinotecan and biological therapy cetuximab. Treatment will occur every 14 days, in either of two ways- Intravenous infusion on Day 1, or intravenous infusion on Day 1 accompanied by 48 hr infusion pump. The treatment will be at physician discretion. The treatment will continue until disease progression, unacceptable toxicity or withdrawal of participant consent. Participants will be followed up for 3 years after beginning the treatment, unless they choose to withdraw from the study prior to that time. Participants who have a low level of AREG and EREG cell markers will be considered ineligible for participation in this study. It is hoped this research will determine whether the combination of cetuximab and irinotecan based treatment is effective for patients with a high level of AREG/EREG cancer cell markers of advanced stage colorectal cancer. If this treatment is found to be effective for participants with a high level of these markers, this method of screening colorectal patients may then be used more frequently to better prescribe treatments to specific patients.
Interventions
Single arm study to explore the efficacy of cetuximab in combination with Irinotecan based treatment in advanced stage RAS/BRAF wild type right sided colorectal cancer with high AREG/EREG expression.
Dosing regimens include either of the following standard of care regimens for the administration of cetuximab in combination with Irinotecan. They will be chosen at physician discretion;
1) Cetuximab 500mg/m2 Intravenous infusion Day 1 of a 14 day cycle in combination with Irinotecan Intravenous in
Single arm study to explore the efficacy of cetuximab in combination with Irinotecan based treatment in advanced stage RAS/BRAF wild type right sided colorectal cancer with high AREG/EREG expression. Dosing regimens include either of the following standard of care regimens for the administration of cetuximab in combination with Irinotecan. They will be chosen at physician discretion; 1) Cetuximab 500mg/m2 Intravenous infusion Day 1 of a 14 day cycle in combination with Irinotecan Intravenous infusion 180mg/m2 Day 1 of a 14 day cycle until disease progression, unacceptable toxicity or withdrawal of consent. 2)Cetuximab 500mg/m2 Intravenous infusion Day 1 of a 14 day cycle in combination with Irinotecan Intravenous infusion 180mg/m2 Day 1 of a 14 day cycle AND Calcium folinate 50mg Intravenous bolus Day 1, Fluorouracil 400mg/m2 Intravenous infusion on Day 1 followed by continuous intravenous infusion Fluorouracil 2400mg/m2 pump over 46 hours until disease progression, unacceptable toxicity or withdrawal of patient consent. Archival tumour tissue from advanced colorectal cancer patients will be tested using an immunohistochemistry assay for Amphiregulin/epiregulin (AREG/EREG)to determine a population of patients who may benefit from this combination of therapy. Participants will be asked to consent to pre- screening of their archival samples for the purpose of AREG/EREG testing. Once consented, testing of archival tissue may take place at any point during the participants first line treatment. There is no time limit for testing results and being considered eligible for the main study. Once AREG/EREG testing results have been received by the site Investigator ,if clinically appropriate the main study participant information and consent form (PICF) will be offered to the participant.
Sponsors
Australasian Gastrointestinal Trials Group
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1.Patients aged greater than 18 years of age 2. ECOG performance status 0-1 3. Patients with advanced colorectal cancer 4. Primary tumour arising from right side of colon (proximal to the splenic flexure) 5. RAS/BRAF wild type 6. Tumours with high AREG/EREG expression as determined by central laboratory testing. 7. At least one measurable lesion as per RECIST 1.1 criteria 8. Receipt of fluoropyrimidine and oxaliplatin containing therapy (FOLFOX,CAPOX or FOLFOXIRI) +/- bevacizumab as part of the initial treatment of advanced disease, or progression within 6 months of completing oxaliplatin based adjuvant therapy for early stage disease 9. Fit for treatment with cetuximab and irinotecan based treatment 10. Life expectancy greater than 3 months
Exclusion criteria
1. Previous exposure to an EGFR inhibitor 2. Grade 2 or greater diarrhoea at time of enrolment 3. Any contraindication to combination treatment with cetuximab + irinotecan based treatment 4. History of another primary cancer within the last 3 years that was either not treated with curative intent or has persisted or relapsed. 5. Patients with multiple primary colorectal cancers 6. Inadequate paraffin tumour sample available for AREG/EREG expression confirmation. 7. Tumours with low AREG/EREG expression levels ( less than 50% tumour cell positivity for either ligand) as determined by central laboratory testing of archival tumour tissue. 8. Inadequate organ function: a. Moderate/severe renal impairment (GFR less than 45 ml/min), as calculated by the Cockcroft-Gault equation b. Absolute neutrophil count less than 1.0x109/L c. Platelet count less than 75x109/L d. Haemoglobin less than 80 g/L (transfusion permitted) e. Aspartate aminotransferase or Alanine aminotransferase greater than 2.5x upper limit of normal, or greater than 5x upper limit of normal if liver metastases are present 9. Medical or psychiatric condition or occupational responsibilities that may preclude compliance with the protocol 10. Participants of child bearing potential unwilling to comply with effective contraceptive use for the duration of the study, including period of screening and 90 days following administration of last dose anti-cancer therapy. 11. Use of any concurrent chemotherapy (excluding irinotecan +/- a fluoropyrimidine), investigational product, biologic or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (e.g. Hormone replacement) is acceptable. Palliative radiotherapy for symptom control is allowed for sites of metastatic disease, which are non-target lesions and not included in RECIST response assessment.
Outcome results
None listed