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Phase II Study of Afinitor vs. Sutent in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma

Information source: Duke University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Advanced Non-clear Cell Renal Cell Carcinoma

Intervention: Everolimus (Drug); Sunitinib (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Duke University

Official(s) and/or principal investigator(s):
Andrew Armstrong, MD, ScM, Principal Investigator, Affiliation: Duke University


To compare the anti-tumor activity of everolimus and sunitinib in subjects with metastatic renal cell carcinoma (mRCC) with non-clear cell pathology.

Clinical Details

Official title: A Randomized Phase II Study of Afinitor (RAD001) vs. Sutent (Sunitinib) in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma (ASPEN)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Anti-tumor activity

Secondary outcome:

Change in progression free survival

PFS expressed in months

Overall response rate

Change in Stable Disease (SD) and Clinical Benefit Rate

Change in overall survival rates

Best tumor shrinkage as a percentile in each arm

Clinical measures of response and PFS with baseline and time-dependent levels of biomarkers

Changes in copy number, RNA expression, and immunohistochemical profiles

median duration of response (CR, PR, and SD)

median OS

time-to-new metastatic disease in each treatment arm

change in quality-of-life

Adverse Events

Detailed description: 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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria: 1. Histologically confirmed advanced Renal Cell Carcinoma (RCC), with non-clear cell pathology. 2. RCC tumor tissue available for correlative sciences, from either primary or metastatic site or both. 3. At the time of screening, at least 4 weeks since prior palliative radiation therapy and/or major surgery, and resolution of all toxic effects of prior therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 4. 0) Grade 1. 4. Subject must have radiographic evidence of metastatic disease with at least 1 measurable per RECIST 1. 1 criteria (Attachment 1)]. 5. Age > 18 years. 6. Adequate laboratory values 7. Karnofsky Performance Status ≥ 60 (Attachment 2). 8. Life expectancy of at least 3 months. 9. Written, signed, dated, and witnessed Institutional Review Board (IRB) or Institutional Ethics Committee (IEC) approved informed consent form (ICF) before any screening procedures are performed. Exclusion Criteria: 1. Subjects with a history of or active central nervous system (CNS) metastases. 2. Prior systemic therapy for RCC, including mTOR and anti-angiogenic therapy, chemotherapy, biologic or experimental therapy. 3. Subjects with collecting duct, medullary, small cell, oncocytoma, or lymphoma-type pathology. 4. Subjects receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers. 5. Major surgery, open biopsy, traumatic injury, or radiotherapy within 4 weeks of the screening visit. 6. Subjects who have not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy. 7. Presence of a non-healing wound or ulcer. 8. Grade 3 hemorrhage within the past month. 9. Hypertension with systolic blood pressure of >180 mm Hg and/or diastolic pressure >100 mm Hg. 10. Subjects with American Heart Association (AHA) Class 2-4 heart disease or any history of congestive heart failure with an ejection fraction <50%, or history of unstable angina, myocardial infarction, coronary artery bypass graft, cerebrovascular accident, transient ischemic attack, or pulmonary embolism within 6 months of entry. 11. Diabetes mellitus with glycosylated hemoglobin A1c (HbgA1c) > 10% despite therapy. 12. A history of interstitial pneumonitis. 13. Subjects with active autoimmune disorder(s) being treated with immunosuppressive agents within 4 weeks prior to the screening visit. 14. Subjects receiving immunosuppressive agents and those with chronic viral/bacterial/fungal illnesses such as human immunodeficiency virus (HIV). 15. Patients who have receive immunization with attenuated live vaccines within one week of study entry or during study period. 16. Patients with active infection(s), active antimicrobial therapy or serious intercurrent illness. 17. History of other prior malignancy in past 5 years. 18. Pregnant or nursing women. 19. Major medical/psychiatric illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study, including inability to absorb oral medications and history of noncompliance to medical regimens. 20. Known hypersensitivity to any of the components in everolimus or sunitinib product 21. Subjects taking agents that significantly prolong the QTc interval are not eligible. 22. Proteinuria with a spot urine protein/creatinine ratio >2 or 24 hour urine protein >2 grams per 24 hours. 23. Severely impaired lung function as defined as spirometry and Carbon Monoxide Diffusing Capacity (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air. 24. Advanced liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).

Locations and Contacts

BC Cancer Agency, Vancouver, British Columbia V5Z 4E6, Canada

Cambridge Cancer Trials Centre, Cambridge, England CB2 0QQ, United Kingdom

The Royal Marsden NHS, London, England 8W3 6JJ, United Kingdom

The Christie Hospital NHS, Manchester, England M20 4BX, United Kingdom

Weston Park Hospital, Sheffield, England S10 2SJ, United Kingdom

University of Chicago, Chicago, Illinois 60637, United States

Indiana University Melvin and Bran Simon Cancer Center, Indianapolis, Indiana 46202, United States

CancerCare Manitoba, Med Onc, Dept Hem and Onc, Winnipeg, Manitoba R3E 0V9, Canada

Karmanos Cancer Institute/Wayne State University, Detroit, Michigan 48201, United States

Washington Univ in St. Louis-School of Medicine, St. Louis, Missouri 63110, United States

Duke Univeristy Medical Center, Durham, North Carolina 27708, United States

Cleveland Clinic, Cleveland, Ohio 44195, United States

London Health Sciences Center, London, Ontario N6A-4L6, Canada

Oregon Health & Science University, Portland, Oregon 97239, United States

Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom

Beatson West Scotland Cancer Centre, Glasgow, Scottland G12 0YN, United Kingdom

SCRI, Nashville, Tennessee 37203, United States

The Vanderbilt Clinic, Henry-Joyce Cancer Center, Nashville, Tennessee 37212, United States

Additional Information

Starting date: September 2010
Last updated: August 3, 2015

Page last updated: August 23, 2015

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