Renal Cell CarcinomaPhase 2NCT00353301
Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma
A Phase 2 study testing Erlotinib hydrochloride and Sirolimus in people with Renal Cell Carcinoma, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The purpose of this study is to test the safety and efficacy of the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™) in the treatment of patients with metastatic kidney cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Erlotinib hydrochloride and Sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2006to Mar 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Who may be able to join
- Signed informed consent to participate in this study.
- Histological diagnosis of renal cell carcinoma.
- Age greater or equal 18 years.
- Eastern Cooperative Oncology Group (ECOG) Performance status of 2 or better.
- Life expectancy of at least 3 months.
- Failure or intolerance to previous treatment with Sutent® and/or Nexavar®.
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- Most recent systemic treatment at least 1 month from the beginning of treatment.
- Most recent local treatment (surgery or irradiation) > 2 weeks from the beginning of treatment.
- At least one site of measurable disease by CT scan or MRI (RECIST criteria).
- Baseline hemoglobin >9 g/dl, platelets > 100,000/mm3, absolute neutrophil count (ANC >1500/mm3.
Who cannot join
- Previous treatment with Tarceva™, Iressa™, Rapamune™, temsirolimus or everolimus.
- Untreated metastasis to the central nervous system.
- Previous solid organ, bone marrow or stem-cell transplant.
- Known AIDS or HIV infection.
- Symptomatic or poorly controlled chronic heart failure.
- Chronic renal failure requiring dialysis on a regular basis.
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- Chronic liver failure.
- Serum aspartate aminotransferase (AST), Alanine Aminotransferase (ALT), alkaline phosphatase or bilirubin >1.5 x the upper limit of normal for the local laboratory.
- Pregnant or breast-feeding women.
- Other invasive malignant diseases within 5 years (other than squamous or basal cell carcinoma of the skin).
- Inability to provide informed consent
- Any other serious and/or unstable medical, psychiatric, or other condition considered by the P.I. to preclude safe or reasonably compliant participation in the protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Hospital
Aurora, Colorado, 80010
About this study
Official title: A Phase II Single Arm Clinical Trial to Evaluate the Efficacy and Safety of the Combination of Tarceva™ (Erlotinib Hydrochloride) and Rapamune™ (Sirolimus) in the Treatment of Metastatic Renal Cell Carcinoma.
The purpose of this study is to test the safety and efficacy of the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™) in the treatment of patients with metastatic kidney cancer.
Read the detailed description
Despite recent advances metastatic renal cell carcinoma remains an incurable condition. Currently available treatment with high-dose interleukin-2 can lead to complete responses in a small minority of selected patients but is markedly toxic and not broadly available. FDA-approved multikinase inhibitors (sorafenib and sunitinib malate) often cause partial and transient tumor regression. There is no standard treatment metastatic renal cell carcinoma for patients whose disease progressed on multikinase inhibitors. The kinase mammalian target of rapamycin (mTOR) is overstimulated in a subset of renal cell carcinomas and other malignancies and can be blocked by sirolimus leading to growth arrest. Erlotinib hydrochloride is a drug that blocks the function of the epidermal growth factor receptor (EGFR), often over expressed in kidney cancer. Sirolimus and EGFR inhibitors and been safely used in combination. In vitro experiments show that erlotinib enhances the sirolimus induced growth impairment in a panel of renal cell carcinoma cells. In the present study patients with metastatic renal cell carcinoma whose disease progressed on multikinase inhibitors will be treated with the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™). This is a single arm trial with no placebo or drug-based control arm
- Conditions
- Renal Cell Carcinoma
- Being tested
- Erlotinib hydrochloride, Sirolimus
- Keywords
- Carcinoma, Renal Cell, Receptor, Epidermal Growth Factor, mTOR protein, Sirolimus, Erlotinib
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Erlotinib hydrochlorideDrug
Also called Tarceva
Patients will receive single-agent Tarceva, 150 mg/day
SirolimusDrug
Also called Rapamune
Patients will receive a loading dose of 6 mg of Rapamune seven days after beginning treatment with Tarceva™ followed by a dose of 2mg/day.
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib and Sirolimus | Experimental | Erlotinib hydrochloride (Tarceva) will be self-administered in an open-label unblinded manner to all patients enrolled in the study. During the treatment period, patients will receive single-agent Tarceva, 150 mg/day.
Sirolimus (Rapamune) will be self-administered in an open-label unblinded manner to all patients enrolled in the study. Patients will receive a loading dose of 6 mg of Rapamune seven days after beginning treatment with Tarceva™ followed by a dose of 2mg/day. Receives: Drug: Erlotinib hydrochloride; Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Time to progression was defined as the time from beginning of therapy until disease progression or death. For subjects who had not progressed at the time of statistical analysis, progression-free survival was censored at the date of their last tumor assessment. Kaplan-Meier method was used to estimate median progression-free survival. Progression was defined as radiographic progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (year 2000 version), non-compliance in obtaining scans, unequivocal clinical progression or the initiation of another medication for the treatment of renal cell carcinoma.
Measured: Physical exam assessments were performed every 4 weeks during the treatment phase. Survival follow-up information was collected every 4 months following the termination visit until death, loss to follow-up, or study termination up to 275 weeks.
Secondary outcomes (1)
Overall Survival
For all subjects who had not died at the time of statistical analysis, duration of survival will was censored at the date of last contact. Kaplan-Meier methodology was used to estimate the magnitude of the treatment effect as described for progression-free survival.
Measured: Survival follow-up information was collected every 4 months following the termination visit until death, loss to follow-up, or study termination up to 275 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2006 (estimated)
- Study startJul 2006
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Thomas W Flaig, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00353301
- Sponsor's protocol ID
- 05-1135.cc
- Status last verified
- Mar 2014
- First submitted
- 14 Jul 2006
- Last updated
- 14 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Gemmill RM, Zhou M, Costa L, Korch C, Bukowski RM, Drabkin HA. Synergistic growth inhibition by Iressa and Rapamycin is modulated by VHL mutations in renal cell carcinoma. Br J Cancer. 2005 Jun 20;92(12):2266-77. doi: 10.1038/sj.bjc.6602646.
PubMed 15956968
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Single Arm Clinical Trial to Evaluate the Efficacy and Safety of the Combination of Tarceva™ (Erlotinib Hydrochloride) and Rapamune™ (Sirolimus) in the Treatment of Metastatic Renal Cell Carcinoma.
- ClinicalTrials.gov ID
- NCT00353301
- Acronym / sponsor ID
- 05-1135.cc
- Conditions
- Renal Cell Carcinoma
- Keywords
- Carcinoma, Renal Cell, Receptor, Epidermal Growth Factor, mTOR protein, Sirolimus, Erlotinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Jul 2006
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 18 Jul 2006 (estimated)
- Results
- Posted 17 Feb 2014
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 test the safety and efficacy of the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™) in the treatment of patients with metastatic kidney cancer.
Detailed description
Despite recent advances metastatic renal cell carcinoma remains an incurable condition. Currently available treatment with high-dose interleukin-2 can lead to complete responses in a small minority of selected patients but is markedly toxic and not broadly available. FDA-approved multikinase inhibitors (sorafenib and sunitinib malate) often cause partial and transient tumor regression. There is no standard treatment metastatic renal cell carcinoma for patients whose disease progressed on multikinase inhibitors. The kinase mammalian target of rapamycin (mTOR) is overstimulated in a subset of renal cell carcinomas and other malignancies and can be blocked by sirolimus leading to growth arrest. Erlotinib hydrochloride is a drug that blocks the function of the epidermal growth factor receptor (EGFR), often over expressed in kidney cancer. Sirolimus and EGFR inhibitors and been safely used in combination. In vitro experiments show that erlotinib enhances the sirolimus induced growth impairment in a panel of renal cell carcinoma cells. In the present study patients with metastatic renal cell carcinoma whose disease progressed on multikinase inhibitors will be treated with the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™). This is a single arm trial with no placebo or drug-based control arm
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erlotinib and Sirolimus | Experimental | Drug: Erlotinib hydrochloride, Drug: SirolimusErlotinib hydrochloride (Tarceva) will be self-administered in an open-label unblinded manner to all patients enrolled in the study. During the treatment period, patients will receive single-agent Tarceva, 150 mg/day. Sirolimus (Rapamune) will be self-administered in an open-label unblinded manner to all patients enrolled in the study. Patients will receive a loading dose of 6 mg of Rapamune seven days after beginning treatment with Tarceva™ followed by a dose of 2mg/day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Signed informed consent to participate in this study.
- Histological diagnosis of renal cell carcinoma.
- Age greater or equal 18 years.
- Eastern Cooperative Oncology Group (ECOG) Performance status of 2 or better.
- Life expectancy of at least 3 months.
Key exclusion criteria (12 listed)
- Previous treatment with Tarceva™, Iressa™, Rapamune™, temsirolimus or everolimus.
- Untreated metastasis to the central nervous system.
- Previous solid organ, bone marrow or stem-cell transplant.
- Known AIDS or HIV infection.
- Symptomatic or poorly controlled chronic heart failure.
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 |
|---|---|---|
| Erlotinib hydrochlorideAlso: TarcevaPatients will receive single-agent Tarceva, 150 mg/day | Drug | Erlotinib and Sirolimus |
| SirolimusAlso: RapamunePatients will receive a loading dose of 6 mg of Rapamune seven days after beginning treatment with Tarceva™ followed by a dose of 2mg/day. | Drug | Erlotinib and Sirolimus |
Primary outcome
Progression-free Survival
Time frame: Physical exam assessments were performed every 4 weeks during the treatment phase. Survival follow-up information was collected every 4 months following the termination visit until death, loss to follow-up, or study termination up to 275 weeks.
Time to progression was defined as the time from beginning of therapy until disease progression or death. For subjects who had not progressed at the time of statistical analysis, progression-free survival was censored at the date of their last tumor assessment. Kaplan-Meier method was used to estimate median progression-free survival. Progression was defined as radiographic progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (year 2000 version), non-compliance in obtaining scans, unequivocal clinical progression or the initiation of another medication for the treatment of renal cell carcinoma.
1 secondary outcome
Overall Survival
Time frame: Survival follow-up information was collected every 4 months following the termination visit until death, loss to follow-up, or study termination up to 275 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15956968Gemmill RM, Zhou M, Costa L, Korch C, Bukowski RM, Drabkin HA. Synergistic growth inhibition by Iressa and Rapamycin is modulated by VHL mutations in renal cell carcinoma. Br J Cancer. 2005 Jun 20;92(12):2266-77. doi: 10.1038/sj.bjc.6602646.
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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.
Thomas W Flaig, MD principal investigator
University of Colorado, Denver
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 Erlotinib hydrochloride and Sirolimus in people with Renal Cell Carcinoma, run by University of Colorado, Denver at 1 site in United States.
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 10 inclusion and 12 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 14 Apr 2014. 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 United States. 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?
Yes. Results are posted in the registry (first posted 17 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression-free Survival (time frame: Physical exam assessments were performed every 4 weeks during the treatment phase. Survival follow-up information was collected every 4 months following the termination visit until death, loss to follow-up, or study termination up to 275 weeks.). 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 NCT00353301, 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 14 Apr 2014.