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

Primary Purpose

Metastatic Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Everolimus
Everolimus
Sponsored by
Herlev Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Metastatic colorectal cancer, Third line therapy, Fourth line therapy, KRAS mutation status, Cetuximab, Everolimus, Irinotecan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Herlev University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cetuximab, everolimus, irinotecan

Cetuximab, everolimus and Irinotecan.

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
June 27, 2011
Last Updated
March 18, 2012
Sponsor
Herlev Hospital
Collaborators
Odense University Hospital, Aalborg University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01387880
Brief Title
Irinotecan, Cetuximab and Everolimus to Patients With Metastatic Colorectal Cancer
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Herlev Hospital
Collaborators
Odense University Hospital, Aalborg University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Metastatic colorectal cancer, Third line therapy, Fourth line therapy, KRAS mutation status, Cetuximab, Everolimus, Irinotecan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cetuximab, everolimus, irinotecan
Arm Type
Experimental
Arm Title
Cetuximab, everolimus and Irinotecan.
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Intervention Description
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
Intervention Name(s)
Everolimus
Intervention Description
1.66 mg per day up to 7½ mg per day
Primary Outcome Measure Information:
Title
Clinical benefit (SD+PR+CR)
Description
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
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benny V Jensen, MD
Organizational Affiliation
University of Copenhagen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Herlev University Hospital
City
Herlev
State/Province
Copenhagen
ZIP/Postal Code
2730
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
30486767
Citation
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.
Results Reference
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Irinotecan, Cetuximab and Everolimus to Patients With Metastatic Colorectal Cancer

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