Protocol Title: Randomised Phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic CRC with either KRAS WT or G13D mutation. ICECREAM: The Irinotecan Cetuximab Evaluation and the Cetuximab Response Evaluation Among Patients with G13D Mutation
Study Chairs: A/Professor Eva Segelov (St Vincent’s Hospital, Sydney NSW); and A/Professor Jeremy Shapiro (Cabrini Haematology & Oncology Centre, Malvern VIC)
Associate Oncology Program Manager: Cheryl Friend
Trial Coordinator: Anna Walsh
Contact Email: ICECREAM@ctc.usyd.edu.au
Detailed information available on the Australian and New Zealand Clinical Trials Registry – ICECREAM
Aim: This study aims to provide important data on the optimal use of currently available therapeutics in patients with metastatic CRC who have progressed on standard chemotherapy options. The trial is designed to study two questions in parallel.
This first is to determine whether cetuximab is optimally used as monotherapy or in combination with an irinotecan-based regimen in KRAS WT patients and the second is to determine whether the efficacy of either cetuximab alone or in combination with an irinotecan-based regimen is similar in patients harbouring a KRAS G13D mutation, as has been suggested by retrospective analysis of several clinical trials.
The results will impact the standard treatment for both groups of patients and may influence the policy on cetuximab administration, including allowing KRAS G13D mutated colorectal cancer patients to have access to treatment that is currently unavailable in Australia.
Background: Patients with metastatic colorectal cancer who have progressed on oxaliplatin and irinotecan containing regimens may benefit from the use of EGFR-inhibiting monoclonal antibodies such as cetuximab, if they contain no mutations in their KRAS gene (ie are wild type (WT)). However, it is unknown whether in this setting these antibodies, such as cetuximab being used in this study, are more efficacious used as monotherapy or in combination with irinotecan, as suggested by the BOND study which did not select for KRAS status.
This study will also provide prospective data on the activity of the EGFR monoclonal antibodies in the subgroup of patients with a specific KRAS mutation in codon G13D. Patients with this specific mutation appear in retrospective analyses to derive similar benefit as WT patients, but currently have no access to the therapy. Therefore this study aims to provide important data on the optimal use of currently available therapeutics in patients with metastatic CRC who have progressed on standard chemotherapy options.
Study Design: This is a phase II, open label, randomised multi-centre trial. Patients will be randomised to receive either cetuximab monotherapy or the combination of cetuximab and irinotecan chemotherapy and will be stratified according to KRAS mutational status (WT vs G13D).
Patients will continue their assigned treatment until disease progression, unless there is unacceptable toxicity or either the patient or physician requests cessation of treatment. 100 patients will be randomised to the study, 50 KRAS WT patients (25 receiving cetuximab monotherapy and 25 receiving cetuximab and irinotecan chemotherapy) and 50 KRAS G13D patients (25 receiving cetuximab monotherapy and 25 receiving cetuximab and irinotecan chemotherapy).
How to perform prestudy gene testing
1. Patients with a known KRAS G13D mutation:
- No need to perform additional mutational testing.
- Can proceed with ICECREAM screening or refer patient to activated site.
2. Patients who have never had a KRAS, BRAF, NRAS and PIK3CA test either:
a) Proceed with KRAS testing at a laboratory of your choice and request testing for BRAF, NRAS and PIC3CA through The University of Melbourne laboratory using this form.
b) Request KRAS, BRAF, NRAS and PIK3CA test through The University of Melbourne laboratory using this form.
3. Patients who are known to be KRAS WT from a test previously performed but have not had BRAF, NRAS and PIC3CA mutation testing please request BRAF, NRAS and PIC3CA mutation testing from The University of Melbourne laboratory using this form.
The panel of mutation testing can be performed at any time, as per clinician preference, but should be done at the latest preferably during the last line of treatment prior to considering ICECREAM, and before progression. Due to time lines, we are suggesting that patients do not begin the 14 day screening procedures until after this result known. Testing for KRAS, BRAF, NRAS and PIK3CA is provided free of cost at the University of Melbourne laboratory.
To view the study schema click here.