Phase II Examination of Irinotecan, Cetuximab and Everolimus to Chemotherapy Resistent Patients With Metastatic Colorectal Cancer and KRAS Mutations or After Progression With KRAS Wildtype on Irinotecan and Cetuximab - Effect and Biological Markers
- Number of patients with progressive disease that obtain disease control defined as the
sum of patients that obtain a Complete Remission (CR), Partial Remission(PR, or stable
- Time to progression after first therapy.
- Length of disease control (CR, PR and SD)
- Survival from date of start of therapy.
- Safety and toxicity of the therapy graded according to Common Toxicity Criteria version
- Influence of smoking on disease control, response, survival and time to progression and
other effect parameters in the investigation.
- Significance of metabolic response evaluated by a Photon Emissions Tomography
- Blood: Examine the influence of potential predictive and prognostic tumour biomarkers
in blood as lactate dehydrogenase (LDH), Carcinoembryonic antigen (CEA), Vascular
endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), Human
Epidermal growth factor Receptor 2 (HER-2), YKL-40, Interleukin-6 (IL-6)
,metallopeptidase inhibitor 1 (TIMP-1), procollagen type I N-terminal propeptide
(PINP), Procollagen type 3 N-terminal propeptide (P3NP), gen-, micro-ribonucleinate
(microRNA)- and protein array profiles, metabolomics and C-reactive protein (CRP) 2
weeks after start of therapy and thereafter every 8.weeks on disease control, response,
survival and time to progression and other parameters investigated.
- Tissue: Examine possible predictive and prognostic biomarkers in tissue from primary
tumour or metastases for micro-RNAarray profiles, mutations in K-RAS, murine sarcoma
viral oncogene homolog (BRAF), Phosphoinositide 3-kinase (PIK3CA), EGFR, tumor protein
53 (p53), and protein expression and polymorphisms of th phosphatase and tensin
homolog (PTEN), epiregulin (EREG), amphiregulin (AREG), Insulin-like growth factor 1
(IGF-1), IGF-1 Receptor (IGF-1R), VEGF, p53, topoisomerase 1 (Topo1), YKL-40, and
- Correlation between possible predictive and prognostic biomarkers in blood and tissue.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Clinical benefit (SD+PR+CR)
Clinical benefit is defined as the number of patients with stable disease lasting 2 months and partial response and CR as defined in RECIST 1.1
Benny V Jensen, MD
University of Copenhagen
Denmark: Centre for Public Health
GI 0923 ICE