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):
Duke University Identifier:
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.

Condition Intervention Phase
Advanced Non-clear Cell Renal Cell Carcinoma
Drug: Everolimus
Drug: Sunitinib
Phase 2

Study Type: Interventional
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:

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

Enrollment: 15
Study Start Date: September 2010
Study Completion Date: February 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Everolimus
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.
Drug: Sunitinib
50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Other Name: Sutent

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.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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).
  Contacts and Locations
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Please refer to this study by its 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 Clinic
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
Canada, Manitoba
CancerCare Manitoba, Med Onc, Dept Hem and Onc
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Ontario
London Health Sciences Center
London, Ontario, Canada, N6A-4L6
United Kingdom
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
Churchill Hospital
Headington, Oxford, United Kingdom, OX3 7LJ
Beatson West Scotland Cancer Centre
Glasgow, Scottland, United Kingdom, G12 0YN
Sponsors and Collaborators
Duke University
Principal Investigator: Andrew Armstrong, MD, ScM Duke University
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Duke University Identifier: NCT01108445     History of Changes
Other Study ID Numbers: Pro00020714  CRAD001L2402T 
Study First Received: April 20, 2010
Last Updated: December 10, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
kidney cancer
renal cancer
papillary renal cell
chromophobe renal cell

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Diseases
Kidney Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Physiological Effects of Drugs processed this record on May 25, 2016