Phase II Study of Afinitor vs. Sutent in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma (ASPEN)
This study has been completed.
Information provided by (Responsible Party):
First received: April 20, 2010
Last updated: December 10, 2015
Last verified: August 2015
To compare the anti-tumor activity of everolimus and sunitinib in subjects with metastatic renal cell carcinoma (mRCC) with non-clear cell pathology.
Advanced Non-clear Cell Renal Cell Carcinoma
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Phase II Study of Afinitor (RAD001) vs. Sutent (Sunitinib) in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma (ASPEN)|
Resource links provided by NLM:
U.S. FDA Resources
Further study details as provided by Duke University:
Primary Outcome Measures:
- Anti-tumor activity [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]The primary objective will be to compare the anti-tumor activity of everolimus and sunitinib in subjects with mRCC with non-clear cell pathology, as measured by progression-free survival (PFS) following treatment initiation according to RECIST criteria.
Secondary Outcome Measures:
- Change in progression free survival [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]6-, 12-, and 24-month rates of PFS in each arm will be compared for each treatment arm.
- PFS expressed in months [ Time Frame: 24 months ] [ Designated as safety issue: No ]Progression-free survival (PFS) expressed in months as compared to an historic control (interferon-treated clear cell RCC control arm from the sunitinib phase III study)
- Overall response rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]Defined as complete response [CR] and partial response [PR] by RECIST criteria in each treatment arm
- Change in Stable Disease (SD) and Clinical Benefit Rate [ Time Frame: 6, 12, 24, 36 months ] [ Designated as safety issue: No ]To compare the Stable Disease and Clinical Benefit Rate (CR+PR+SD >12 months) at 6, 12, 24, and 36 months in each treatment arm.
- Change in overall survival rates [ Time Frame: 6, 12, 24, 36 months, and until death ] [ Designated as safety issue: No ]To compare overall survival (OS) rates at 6, 12, 24, and 36 months and over time in each treatment arm.
- Best tumor shrinkage as a percentile in each arm [ Time Frame: 24 months ] [ Designated as safety issue: No ]To compare the best tumor shrinkage as a percentile in each treatment arm.
- Clinical measures of response and PFS with baseline and time-dependent levels of biomarkers [ Time Frame: 36 months ] [ Designated as safety issue: No ]To correlate clinical measures of response and PFS with baseline and time-dependent levels of biomarkers. These biomarkers include plasma angiokine levels, tissue immunohistochemical and genomic profiles, copy number as assessed by array-based comparative genomic hybridization (CGH), and known mutations in non-clear cell RCC
- Changes in copy number, RNA expression, and immunohistochemical profiles [ Time Frame: 36 months ] [ Designated as safety issue: No ]To evaluate in an exploratory fashion changes in copy number, RNA expression, and immunohistochemical profiles by microarray between primary non-clear cell RCC tumors and metastatic samples
- median duration of response (CR, PR, and SD) [ Time Frame: 24 months ] [ Designated as safety issue: No ]To compare the median duration of response (CR, PR, and SD) in each treatment arm.
- median OS [ Time Frame: 36 months ] [ Designated as safety issue: No ]To compare the median OS in each treatment arm.
- time-to-new metastatic disease in each treatment arm [ Time Frame: 24 months ] [ Designated as safety issue: No ]To compare the time-to-new metastatic disease in each treatment arm, defined from the date of first study agent administration to the onset of a new evaluable site of disease, excluding the primary site and all sites documented at baseline
- change in quality-of-life [ Time Frame: baseline, cycle 2, cycle 4, cycle 6, cycle 8, cycle 10 ] [ Designated as safety issue: No ]To compare change in quality-of-life, as measured by the FACT-KSI scale at baseline and every 2 cycles for up to 10 cycles per subject in each treatment arm
- Adverse Events [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]To assess toxicities associated with everolimus or sunitinib using NCI CTC version 4.0 criteria
|Study Start Date:||September 2010|
|Study Completion Date:||February 2015|
|Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
Active Comparator: RAD001
Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.
Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.
Other Name: Afinitor, everolimus, RAD001
Active Comparator: Sunitinib
Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Other Name: Sutent
This will be an international (USA, Canada, and UK) open-label, outpatient, multicenter, randomized study of treatment with RAD001 (everolimus (Afinitor®) or sunitinib (Sutent®) in subjects with mRCC and non-clear cell histology. Special emphasis is placed on papillary and chromophobe histologies while sarcomatoid clear cell variants, medullary, and collecting duct carcinomas will be excluded (see eligibility). Subjects may continue receiving study drugs until disease progression, unacceptable toxicities, or withdrawal of consent, for a maximum of 24 months. Continuation of study assigned treatment will be allowed beyond 24 months at the discretion of the sponsor. Stratification variables will include histology (papillary vs. chromophobe) and Motzer risk criteria (0, 1-2, and 3). Tumor progression will be assessed locally and by independent review, in strict accordance with Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria measured every 12 weeks. At the time of progression, subjects will be taken off study other than simple administrative mortality follow-up. Primary pathologic samples and plasma/urine angiokine levels at baseline and over time will be collected and stored centrally for biomarker analysis.
Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01108445
Please refer to this study by its ClinicalTrials.gov identifier: NCT01108445
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Indiana|
|Indiana University Melvin and Bran Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|United States, Michigan|
|Karmanos Cancer Institute/Wayne State University|
|Detroit, Michigan, United States, 48201|
|United States, Missouri|
|Washington Univ in St. Louis-School of Medicine|
|St. Louis, Missouri, United States, 63110|
|United States, North Carolina|
|Duke Univeristy Medical Center|
|Durham, North Carolina, United States, 27708|
|United States, Ohio|
|Cleveland, Ohio, United States, 44195|
|United States, Oregon|
|Oregon Health & Science University|
|Portland, Oregon, United States, 97239|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|The Vanderbilt Clinic, Henry-Joyce Cancer Center|
|Nashville, Tennessee, United States, 37212|
|Canada, British Columbia|
|BC Cancer Agency|
|Vancouver, British Columbia, Canada, V5Z 4E6|
|CancerCare Manitoba, Med Onc, Dept Hem and Onc|
|Winnipeg, Manitoba, Canada, R3E 0V9|
|London Health Sciences Center|
|London, Ontario, Canada, N6A-4L6|
|Cambridge Cancer Trials Centre|
|Cambridge, England, United Kingdom, CB2 0QQ|
|The Royal Marsden NHS|
|London, England, United Kingdom, 8W3 6JJ|
|The Christie Hospital NHS|
|Manchester, England, United Kingdom, M20 4BX|
|Weston Park Hospital|
|Sheffield, England, United Kingdom, S10 2SJ|
|Headington, Oxford, United Kingdom, OX3 7LJ|
|Beatson West Scotland Cancer Centre|
|Glasgow, Scottland, United Kingdom, G12 0YN|
Sponsors and Collaborators
|Principal Investigator:||Andrew Armstrong, MD, ScM||Duke University|