Metastatic Colorectal CancerPhase 2TIRASMUSNCT00827684
Temsirolimus and Irinotecan for Treatment Resistant Patients With Metastatic Colorectal Cancer and KRAS Mutations
A Phase 2 study testing Irinotecan and Temsirolimus in people with Metastatic Colorectal Cancer, run by Vejle Hospital at 2 sites in Denmark.
Trial summary
The purpose of this study is to investigate the safety and efficacy of temsirolimus as a single drug, and of temsirolimus in combination with irinotecan in chemotherapy resistant patients with KRAS mutated colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Irinotecan and Temsirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesDenmark
- Study dates
- Mar 2009to Jun 2011
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically verified colorectal adenocarcinomas
- Age > 18 years and < 70
- Metastatic colorectal cancer refractory 5-FU, oxaliplatin and irinotecan containing treatment regimes
- KRAS mutation detected by DxS kit in primary tumor or metastatic lesion.
- Measurable disease according to RECIST
- ECOG performance status 0, 1 or 2
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- Adequate renal, hepatic and haematological function
- Normal serum cholesterol and triglycerides
- Blood samples and available paraffin embedded tumor material for translational research studies
- Fertile males and females (< 2 years after last period for women) must use effective birth control
- Signed Informed consent
Who cannot join
- Clinically significant heart disease, active severe infections or other concurrent disease
- Other malignant diseases within 5 years of inclusion in the study, except basal cell squamous cell carcinoma of the skin and cervical carcinoma-in-situ
- Prior radiotherapy within 30 days of treatment start
- Other experimental therapy within 30 days of treatment initiation
- Patients who are breast feeding, childbearing or of childbearing potential without using dual effective contraception
- Clinical or radiological evidence of CNS metastasis
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- Completed any major surgery, excision biopsy or significant traumatic lesion ≥ 4 weeks from start of treatment and completed any minor surgery ≥ 1 week prior to start of treatment
- Insertion of a vascular access device is not considered major or minor surgery from the viewpoint of protocol eligibility
- Patients must have fully recovered from the procedure and have a fully healed incision
- Planned radiation therapy against target-lesions
- Patients with significant non-healing wounds or ulcers
- History or evidence of thrombotic or hemorrhagic disorders
- Significant haemorrhage (> 30 ml/bleeding episode in previous 3 months)
- Haemoptysis (> 5 ml fresh blood in previous 4 weeks)
- Patients on full-dose anticoagulation (e.g., warfarin) are eligible provided that both of the following criteria are met:
- The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or is on a stable dose of low molecular weight heparin
- The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
- Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub-Arachnoid Hemorrhage (SAH) within 12 months prior to randomization
- No known or history of HIV seropositivity
- The use of ACE inhibitors is not permitted during the study
- Known allergy to temsirolimus, sirolimus, polysorbate 80 or included agents.
- Agents with strong CYP3A4-inhibitory potential
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites
Rigshospitalet, Department of Oncology
Copenhagen, DK-2100
Vejle Hospital, Dept. of Oncology
Vejle
About this study
Official title: Phase II Study of Temsirolimus and Irinotecan in Chemotherapy Refractory Patients With KRAS Mutated Metastatic Colorectal Cancer
The purpose of this study is to investigate the safety and efficacy of temsirolimus as a single drug, and of temsirolimus in combination with irinotecan in chemotherapy resistant patients with KRAS mutated colorectal cancer.
Read the detailed description
Chemotherapy resistance is a major challenge in metastatic colorectal cancer (mCRC), and EGFR inhibitors have been introduced as 3rd line treatment to chemotherapy refractory patients. However, it has recently been established that response to treatment with irinotecan and cetuximab is confined to patients with wtKRAS tumors. Therefore, downstream targets are being proposed as potential inhibitors of the EGFR signalling in tumours with KRAS mutations. mTOR is a central intracellular signalling molecule and a rational approach for potential reversion of chemotherapy resistance in these patients.
Preclinical data suggest that different solid tumors could respond to mTOR inhibitors and report on enhanced antitumor activity in combination with different traditional cytostatic drugs. Furthermore recent preclinical data suggest that mTOR inhibition may induce tumor reduction in colon cancer xenographs. Temsirolimus (CCI-779) has been widely investigated in different clinical settings and is presently registered for treatment of renal cell carcinomas. Furthermore, is has recently shown response in metastatic breast cancer patients, but at present there are no clinical data on efficacy or safety in metastatic colorectal cancer patients.
The present study aims at investigating the safety and efficacy of monotherapy temsirolimus and a combination of temsirolimus and irinotecan in chemotherapy resistant, KRAS mutated colorectal adenocarcinomas.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Irinotecan, Temsirolimus
- Keywords
- KRAS mutation
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IrinotecanDrug
TemsirolimusDrug
| Study group | Role | What they receive |
|---|---|---|
| Response or stable disease | Active comparator | will receive Temsirolimus Receives: Drug: Temsirolimus |
| Progression | Experimental | Will receive a combination of Temsirolimus and Irinotecan Receives: Drug: Irinotecan; Drug: Temsirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rates
Secondary outcomes (3)
Progression free survival
Overall survival
Translational Research
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2009 (estimated)
- Study startMar 2009
- Primary completionJan 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vejle Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Anders Jakobsen, MD, DMSc, Study chair, Vejle HospitalKaren-Lise G Spindler, MD, PhD, Principal investigator, Vejle Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00827684
- Sponsor's protocol ID
- 2008-007665-22
- Other IDs
- 2008
- Acronym
- TIRASMUS
- Status last verified
- Jun 2011
- First submitted
- 22 Jan 2009
- Last updated
- 8 Jun 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Temsirolimus and Irinotecan in Chemotherapy Refractory Patients With KRAS Mutated Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00827684
- Acronym / sponsor ID
- TIRASMUS / 2008-007665-22
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- KRAS mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Vejle HospitalUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 23 Jan 2009 (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.
The purpose of this study is to investigate the safety and efficacy of temsirolimus as a single drug, and of temsirolimus in combination with irinotecan in chemotherapy resistant patients with KRAS mutated colorectal cancer.
Detailed description
Chemotherapy resistance is a major challenge in metastatic colorectal cancer (mCRC), and EGFR inhibitors have been introduced as 3rd line treatment to chemotherapy refractory patients. However, it has recently been established that response to treatment with irinotecan and cetuximab is confined to patients with wtKRAS tumors. Therefore, downstream targets are being proposed as potential inhibitors of the EGFR signalling in tumours with KRAS mutations. mTOR is a central intracellular signalling molecule and a rational approach for potential reversion of chemotherapy resistance in these patients.
Preclinical data suggest that different solid tumors could respond to mTOR inhibitors and report on enhanced antitumor activity in combination with different traditional cytostatic drugs. Furthermore recent preclinical data suggest that mTOR inhibition may induce tumor reduction in colon cancer xenographs. Temsirolimus (CCI-779) has been widely investigated in different clinical settings and is presently registered for treatment of renal cell carcinomas. Furthermore, is has recently shown response in metastatic breast cancer patients, but at present there are no clinical data on efficacy or safety in metastatic colorectal cancer patients.
The present study aims at investigating the safety and efficacy of monotherapy temsirolimus and a combination of temsirolimus and irinotecan in chemotherapy resistant, KRAS mutated colorectal adenocarcinomas.
Study design
- Primary purpose
- Treatment
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Response or stable disease | Active comparator | Drug: Temsirolimuswill receive Temsirolimus |
| Progression | Experimental | Drug: Irinotecan, Drug: TemsirolimusWill receive a combination of Temsirolimus and Irinotecan |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically verified colorectal adenocarcinomas
- Age > 18 years and < 70
- Metastatic colorectal cancer refractory 5-FU, oxaliplatin and irinotecan containing treatment regimes
- KRAS mutation detected by DxS kit in primary tumor or metastatic lesion.
- Measurable disease according to RECIST
Key exclusion criteria (22 listed)
- Clinically significant heart disease, active severe infections or other concurrent disease
- Other malignant diseases within 5 years of inclusion in the study, except basal cell squamous cell carcinoma of the skin and cervical carcinoma-in-situ
- Prior radiotherapy within 30 days of treatment start
- Other experimental therapy within 30 days of treatment initiation
- Patients who are breast feeding, childbearing or of childbearing potential without using dual effective contraception
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 |
|---|---|---|
| Irinotecan | Drug | Progression |
| Temsirolimus | Drug | Progression, Response or stable disease |
Primary outcome
Objective response rates
3 secondary outcomes
Progression free survival
Overall survival
Translational Research
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 8 Jun 2011.
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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.
Anders Jakobsen, MD, DMSc study chair
Vejle Hospital
Karen-Lise G Spindler, MD, PhD principal investigator
Vejle Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Irinotecan and Temsirolimus in people with Metastatic Colorectal Cancer, run by Vejle Hospital at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 22 exclusion criteria. 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 8 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Objective response rates. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Jun 2011.