Irinotecan, Cetuximab and Everolimus to Patients With Metastatic Colorectal Cancer

NCT ID: NCT01387880

Last Updated: 2012-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2012-03-31

Brief 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.

Detailed 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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuximab, everolimus, irinotecan

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

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

Intervention Type: DRUG

1.66 mg per day up to 7½ mg per day

Cetuximab, everolimus and Irinotecan.

Patients with metastatic colorectal cancer with KRAS mutant tumours are treated with cetuximab, everolimus and irinotecan.

Patients with KRAS wildtype colorectal cancer that have progressed on therapy with cetuximab and irinotecan are treated with cetuximab, irinotecan and everolimus.

Group Type: ACTIVE_COMPARATOR

Everolimus

Intervention Type: DRUG

1.66 mg per day up to 7½ mg per day

Interventions

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.

Intervention Type: DRUG

Everolimus

1.66 mg per day up to 7½ mg per day

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Odense University Hospital

OTHER

Sponsor Role: collaborator

Aalborg University Hospital

OTHER

Sponsor Role: collaborator

Herlev Hospital

OTHER

Sponsor Role: lead

Responsible Party

Benny Vittrup Jensen

onsultant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Benny V Jensen, MD

Role: PRINCIPAL_INVESTIGATOR

University of Copenhagen

Locations

Herlev University Hospital

Herlev, Copenhagen, Denmark

Countries

Denmark

References

Spindler KG, Demuth C, Sorensen BS, Johansen JS, Nielsen D, Pallisgaard N, Hoegdall E, Pfeiffer P, Vittrup Jensen B. Total cell-free DNA, carcinoembryonic antigen, and C-reactive protein for assessment of prognosis in patients with metastatic colorectal cancer. Tumour Biol. 2018 Nov;40(11):1010428318811207. doi: 10.1177/1010428318811207.

Reference Type: DERIVED

PMID: 30486767 (View on PubMed)

Other Identifiers

GI 0923 ICE

Identifier Type: -

Identifier Source: org_study_id