Clinical trial NCT01108445: Phase II Study of Afinitor vs. Sutent in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Non-clear Cell Renal Cell Carcinoma
Keywords: cancer
kidney cancer
sutent
everolimus
renal cancer
papillary renal cell
chromophobe renal cell
papillary
chromophobe
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Novartis
name: Pfizer
First posted: 2010-04-22
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Anti-tumor Activity as Measured by Median Progression Free Survival Time
timeFrame: 24 Months
Secondary outcomes:
measure: Progression Free Survival Rates
timeFrame: 6, 12 and 24 months
measure: PFS Expressed in Months
timeFrame: 24 months
measure: Overall Response Rate
timeFrame: 24 months
measure: Percentage of Participants With Stable Disease (SD)
timeFrame: Baseline to 36 months
measure: 12 Week Clinical Benefit Rate as Percentage
timeFrame: Baseline to 36 months
measure: Overall Survival Rates
timeFrame: 6, 12, 24, 36 months
measure: Best Tumor Shrinkage as a Percentile in Each Arm
timeFrame: 24 months
measure: Median Duration of Response (CR, PR, and SD)
timeFrame: 24 months
measure: Median OS
timeFrame: Up to 40 months
measure: Time-to-new Metastatic Disease in Each Treatment Arm
timeFrame: 36 months
measure: Percentage of Participants With Adverse Events
timeFrame: 24 months
measure: Change in Quality-of-life
timeFrame: baseline, cycle 3 day 1
measure: Change in Quality-of-life
timeFrame: baseline, cycle 6 day 1
measure: Change in Quality-of-life
timeFrame: baseline, up to 40 months
Other outcomes:
measure: Clinical Measures of Response and PFS With Baseline and Time-dependent Levels of Biomarkers
timeFrame: 36 months
measure: Changes in Copy Number, RNA Expression, and Immunohistochemical Profiles
timeFrame: 36 months
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bran Simon Cancer Center
state: Indiana
city: Detroit
country: United States
facility: Karmanos Cancer Institute/Wayne State University
state: Michigan
city: Saint Louis
country: United States
facility: Washington Univ in St. Louis-School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke Univeristy Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: SCRI
state: Tennessee
city: Nashville
country: United States
facility: The Vanderbilt Clinic, Henry-Joyce Cancer Center
state: Tennessee
city: Vancouver
country: Canada
facility: BC Cancer Agency
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba, Med Onc, Dept Hem and Onc
state: Manitoba
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Cambridge
country: United Kingdom
facility: Cambridge Cancer Trials Centre
state: England
city: London
country: United Kingdom
facility: The Royal Marsden NHS
state: England
city: Manchester
country: United Kingdom
facility: The Christie Hospital NHS
state: England
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
state: England
city: Headington
country: United Kingdom
facility: Churchill Hospital
state: Oxford
city: Glasgow
country: United Kingdom
facility: Beatson West Scotland Cancer Centre
state: Scottland
Study officials:
affiliation: Duke University
name: Andrew Armstrong, MD, ScM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, Garcia JA, Vaishampayan UN, Picus J, Hawkins RE, Hainsworth JD, Kollmannsberger CK, Logan TF, Puzanov I, Pickering LM, Ryan CW, Protheroe A, Lusk CM, Oberg S, George DJ. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol. 2016 Mar;17(3):378-388. doi: 10.1016/S1470-2045(15)00515-X. Epub 2016 Jan 13.
citation: Winquist E, Rodrigues G. Open clinical uro-oncology trials in Canada. Can J Urol. 2012 Dec;19(6):6587-91. No abstract available.