Back to resultsErlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma
Primary Purpose
Renal Cell Carcinoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Erlotinib hydrochloride
Sirolimus
Sponsored by
About this trial
This is an interventional treatment trial for Renal Cell Carcinoma focused on measuring Carcinoma, Renal Cell, Receptor, Epidermal Growth Factor, mTOR protein, Sirolimus, Erlotinib
Eligibility Criteria
Inclusion Criteria: 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®. 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. Exclusion Criteria: 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. 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.
Sites / Locations
- University of Colorado Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Erlotinib and Sirolimus
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT00353301
First Posted
July 14, 2006
Last Updated
March 17, 2014
Sponsor
University of Colorado, Denver
Collaborators
Genentech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00353301
Brief Title
Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma
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.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
July 2006 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
March 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
Genentech, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Cell Carcinoma
Keywords
Carcinoma, Renal Cell, Receptor, Epidermal Growth Factor, mTOR protein, Sirolimus, Erlotinib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Erlotinib and Sirolimus
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Erlotinib hydrochloride
Other Intervention Name(s)
Tarceva
Intervention Description
Patients will receive single-agent Tarceva, 150 mg/day
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
Rapamune
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
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.
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.
Secondary Outcome Measure Information:
Title
Overall Survival
Description
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.
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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®.
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.
Exclusion Criteria:
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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas W Flaig, MD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80010
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
15956968
Citation
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.
Results Reference
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Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma
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