Irinotecan, Cetuximab and Everolimus to Patients With Metastatic Colorectal Cancer (ICE)

March 18, 2012 updated by: Benny Vittrup Jensen, Herlev Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Copenhagen
      • Herlev, Copenhagen, Denmark, 2730
        • Herlev University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cetuximab, everolimus, irinotecan
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.

Drug: Everolimus
1.66 mg per day up to 7½ mg per day
Active Comparator: 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.
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.

Drug: Everolimus
1.66 mg per day up to 7½ mg per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical benefit (SD+PR+CR)
Time Frame: 1 year
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Herlev Hospital

Collaborators

Odense University Hospital
Aalborg University Hospital

Investigators

  • Principal Investigator: Benny V Jensen, MD, University of Copenhagen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

June 27, 2011

First Submitted That Met QC Criteria

July 5, 2011

First Posted (Estimate)

July 6, 2011

Study Record Updates

Last Update Posted (Estimate)

March 20, 2012

Last Update Submitted That Met QC Criteria

March 18, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GI 0923 ICE

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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