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. 2023 May 4;2023(5):CD013798. doi: 10.1002/14651858.CD013798.pub2

NCT01108445.

Study characteristics
Methods Study name: ASPEN
Study design: a two‐arm RCT, phase II
Blinding: none, open‐label
Study dates: Between Sept 23, 2010, and Oct 28, 2013 (date of randomisation)
Date of data cut‐off: December, 2014 (database lock)
Location: 3 countries (Canada, UK, USA), types of centres: medical centres/agencies, clinics, hospitals, (18 study locations)
Cross‐over study or cross over permitted: not a cross‐over study per design, but cross over was permitted upon progression (from sunitinib to everolimus)
Participants Inclusion criteria:

  • histologically confirmed advanced RCC, with non‐clear cell pathology

  • 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 NCI Common Terminology Criteria for Adverse Events Grade 1

  • participant must have radiographic evidence of metastatic disease with at least 1 measurable per RECIST 1.1 criteria

  • age > 18 years

  • KPS ≥ 60

  • life expectancy of at least 3 months


Exclusion criteria:

  • participants with a history of or active CNS metastases

  • prior systemic therapy for RCC, including mTOR and anti‐angiogenic therapy, chemotherapy, biologic or experimental therapy

  • participants receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers

  • participants receiving immunosuppressive agents and those with chronic viral/bacterial/fungal illnesses such as HIV

  • history of other prior malignancy in past 5 years

  • known hypersensitivity to any of the components in everolimus or sunitinib product


Sample size: 131 participants signed consent. 22 were screen failures. 1 withdrew consent prior to being randomised. 108 participants were randomised.
Age (years, median with range): experimental arm: 64 (29‐90), control arm: 59 (24‐100)
Sex (m/f): experimental arm: 44/13, control arm: 37/14
Prognostic factors:

  • MSKCC risk group (0, 1‐2, ≥3) (%)

    • experimental arm:

      • 0 14 (25),

      • 1‐2 32 (56),

      • ≥3 11 (19)

    • control arm:

      • 0 15 (29),

      • 1‐2 32 (63),

      • ≥3 4 (8)

  • Prior nephrectomy (n, %)

    • Yes

      • experimental arm: 45 (79), control arm: 41 (80)
Interventions Experimental arm (n= 57): everolimus (10 mg, oral, once/day)
Control arm (n= 51): sunitinib (50 mg, oral, once/day)
Treatment was four weeks on treatment, two weeks off treatment (one cycle = six weeks).
Outcomes Primary outcome(s)

  • Anti‐tumor activity as measured by median PFS time

    • Time frame: 24 months


Secondary outcome(s)

  • PFS rates

    • Time frame: 6, 12, and 24 months

  • PFS expressed in months

    • Time frame: 24 Months

  • OSR

    • Time frame: 6, 12, 24, 36 months

  • Median OS

    • Time frame: up to 40 months

  • Percentage of participants with AEs

    • Time frame: 24 months

  • QoL

    • Time frame: baseline up to 40 months

  • Number of participants who discontinued treatment due to an AE


Relevant to this review but not reported: TFST
Other outcomes (not relevant to this review): Time‐to‐new metastatic disease, DoR, tumour shrinkage, clinical benefit rate, SD, ORR
Notes Funding: Novartis and Pfizer
Declaration of Interest: Quote: "AJA and DJG reports grants from Novartis and Pfizer during the conduct of the study; grants and personal fees from Dendreon, Sanofi ‐Aventis, Bayer, Medivation/Astellas, and Janssen, outside the submitted work. DJG also reports grants from Innocrin and Exelixis and personal fees from BMS and Janssen. TE is an employee of AstraZeneca and reports grants from AstraZeneca, personal fees from Novartis, Roche, BMS, and AVEO, grants from Bayer, grants and personal fees from Pfizer, GSK, personal fees and grant to institution from Astellas, outside the submitted work. JAG reports grants and personal fees from Pfizer and Novartis, during the conduct of the study; grants and personal fees from Bayer and Medivation/Astellas, and personal fees from Sanofi‐Aventis, outside the submitted work. TFL reports grants from Novartis and Pfizer, during the conduct of the study; grants from Abbott, Abraxis, Acceleron, Amgen, AstraZeneca, Biovex, and Cerulean, Eisai, Eli Lilly grants and personal fees from Argos and Aveo, Bristol‐Myers Squibb, Celgene, GlaxoSmithKline, Hoffman‐La Roche, Immatics, Merck, Roche, Synta, Threshold, Tracon, EMD Serono, Millennium, and Schering‐Plough, personal fees from Genentech, and grants and personal fees from Novartis, Pfizer, Prometheus, and Wyeth, outside the submitted work. CKK reports personal fees from Pfizer, Novartis, BMS, and Sanofi‐Aventis, outside the submitted work. UNV reports grants and personal fees from Novartis and Pfizer, outside the submitted work. CWR reports personal fees from Pfizer and Genentech, research grant to institution from Onyx, outside the submitted work. RJJ reports grants from Pfizer and Novartis, during the conduct of the study; grants and personal fees from Pfizer, and grants, personal fees, and non‐financial support from Novartis and GSK, outside the submitted work. WMS reports grants and personal fees from Pfizer, outside the submitted work. LMP reports personal fees from Pfizer and Novartis. SH, SB, JP, REH, JDH, IP, AP, CML, and SO declare no competing interests."
Clinical study report available: no
Study protocol available: no
Statistical analysis plan available: no