Metastatic Colorectal CancerPhase 2ICENCT01387880
Irinotecan, Cetuximab and Everolimus to Patients With Metastatic Colorectal Cancer
A Phase 2 study testing Everolimus in people with Metastatic Colorectal Cancer, run by Herlev Hospital at 1 site in Denmark.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteDenmark
- Study dates
- Jan 2010to Mar 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- Everolimus
- Keywords
- Metastatic colorectal cancer, Third line therapy, Fourth line therapy, KRAS mutation status, Cetuximab, Everolimus, Irinotecan
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
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.
EverolimusDrug
1.66 mg per day up to 7½ mg per day
| Study group | Role | What they receive |
|---|---|---|
| Cetuximab, everolimus, irinotecan | Experimental | Not described Receives: Drug: Everolimus |
| Cetuximab, everolimus and Irinotecan. | Active comparator | 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. Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2011 (estimated)
- Study startJan 2010
- Primary completionNov 2011
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herlev Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Odense University Hospital, Aalborg University Hospital
- Responsible party
- Principal investigator, Benny Vittrup Jensen, Herlev Hospital
- Investigators
- Benny V Jensen, MD, Principal investigator, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01387880
- Sponsor's protocol ID
- GI 0923 ICE
- Acronym
- ICE
- Status last verified
- Mar 2012
- First submitted
- 27 Jun 2011
- Last updated
- 20 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 30486767
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01387880
- Acronym / sponsor ID
- ICE / GI 0923 ICE
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Metastatic colorectal cancer, Third line therapy, Fourth line therapy, KRAS mutation status, Cetuximab, Everolimus, Irinotecan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Herlev HospitalUniversity, hospital or other
- Collaborators
- Odense University Hospital, Aalborg University Hospital
- Study start
- Jan 2010
- Primary completion
- Nov 2011 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 6 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cetuximab, everolimus, irinotecan | Experimental | Drug: Everolimus |
| Cetuximab, everolimus and Irinotecan. | Active comparator | Drug: EverolimusPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusPatients 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 | Cetuximab, everolimus, irinotecan |
| Everolimus1.66 mg per day up to 7½ mg per day | Drug | Cetuximab, everolimus and Irinotecan., Cetuximab, everolimus, irinotecan |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2012.
- Derived from this study: PubMed 30486767Spindler 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benny V Jensen, MD principal investigator
University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus in people with Metastatic Colorectal Cancer, run by Herlev Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical benefit (SD+PR+CR) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01387880, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2012.