Irinotecan, Cetuximab and Everolimus to Patients With Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

— ICE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01387880
• Other study ID #: GI 0923 ICE
• Status: Completed
• Phase: Phase 2
• First received: June 27, 2011
• Last updated: March 18, 2012
• Start date: January 2010
• Est. completion date: March 2012

Study information

• Verified date: March 2012
• Source: Herlev Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Centre for Public HealthDenmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This is an open, multicenter phase II trial of therapy with a combination of cetuximab, and irinotecan every second week combined with a daily dose of everolimus to patients with metastatic colorectal cancer with Kirsten rat sarcoma viral oncogene (KRAS) mutation or to patients resistent to cetuximab and irinotecan therapy for metastatic colorectal cancer.

Description:

Main objective:

• 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 disease (SD))

Secondary objectives:

• 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 3.0

• 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 (PET)/Computer Tomography(CT)scan.

• 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 TIMP-1

• Correlation between possible predictive and prognostic biomarkers in blood and tissue.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: March 2012
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Criteria for inclusion:

• Patients with a histological or cytological verified adenocarcinoma of the colon or rectum with non-resectable or metastatic cancer.

• Patients with measurable disease without previous radiotherapy

• Patients with metastatic colorectal cancer with progression after previous therapy with 5-fluoropyrimidines, oxaliplatin or irinotecan. Patients should have been treated with oxaliplatin, but if oxaliplatin has be contraindicated or not tolerated the patient can participate in the trial.

• Patients with KRAS-mutation in their primary tumour or metastasis.

• Patients with progression after therapy with irinotecan or cetuximab independent of KRAS mutation status.

• Previous radiotherapy is allowed to less than 25 % of the bone marrow.

• Age more or equal to 18 years.

• Performance status less than 3.

• An expected survival time of at least 3 months.

• Signed informed consent according to specifications from the ethical comites.

Criteria for exclusion:

• Former or other concurrent malignant disease except treated basal cell carcinoma or in situ cervical cancer.

• No cytotoxic therapy or other experimental treatment within 28 days before inclusion.

• No former therapy with everolimus or other rapamycin as sirolimus or temsirolimus.

• No known hypersensitivity for one or more components in the therapy.

• No uncontrolled diabetes

• No serious non-healing wounds, gastric ulcers, bone fractures, greater surgical procedures, major traumatic injuries within 28 days before inclusion.

• No ongoing bleeding or pathological condition associated with a risk of bleeding.

• No liver disease as cirrhose, chronical active hepatitis or chronic persistent hepatitis.

• No gastrointestinal disturbances in function that might cause a major change in the absorption of everolimus as ulcerative disease, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome.

• No planned immunisation with attenuated virus in the study period.

• Patients that is unable to follow treatment or evaluation plan.

• Every condition or therapy that after the judgement of investigator might infer the patient a risk or influence the trials objective.

• Pregnant or breastfeeding women.

• At fertile women this is insured by a negative test of pregnancy or use of a safe anticonception during the trial period and at least 3 months after end of treatment.

• Patients with active infections or other serious medical co-morbidity, that might prevent the patient from being treated with the protocoled therapy.

• Incapacitated

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Everolimus
Patients with KRAS mutant tumours are treated with cetuximab, everolimus and irinotecan as third line. Patients with KRAS wildtype tumours that have progressed on therapy with cetuximab and irinotecan are treated with cetuximab, everolimus and Irinotecan.
• Everolimus
1.66 mg per day up to 7½ mg per day

Locations

Country	Name	City	State
Denmark	Herlev University Hospital	Herlev	Copenhagen

Sponsors (3)

Lead Sponsor	Collaborator
Herlev Hospital	Aalborg Universitetshospital, Odense University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	1 year	No