Methods: In this open-label, multicenter (n = 13), parallel-arm, phase II study (ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd–IFNα/Syn3 (randomly assigned 1:1 to 1 × 1011 viral particles (vp)/mL or 3 × 1011 vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses.
Results: Forty patients received rAd–IFNα/Syn3 (1 × 1011 vp/mL, n = 21; 3 × 1011 vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd–IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%).
Conclusion: Ad—IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy.
Clinical Trial Information: NCT01687244
Neal D. Shore, Stephen A. Boorjian, Daniel J. Canter, Kenneth Ogan, Lawrence I. Karsh, Tracy M. Downs, Leonard G. Gomella, Ashish M. Kamat, Yair Lotan, Robert S. Svatek, Trinity J. Bivalacqua, Robert L. Grubb, III, Tracey L. Krupski, Seth P. Lerner, Michael E. Woods, Brant A. Inman, Matthew I. Milowsky, Alan Boyd, F. Peter Treasure, Gillian Gregory, David G. Sawutz, Seppo Yla-Herttuala, Nigel R. Parker, and Colin P.N. Dinneycorresponding author
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Neal D. Shore, Carolina Urologic Research Center, Myrtle Beach, SC; Stephen A. Boorjian, Mayo Clinic, Rochester, MN; Daniel J. Canter, Ochsner Health System, New Orleans, LA; Kenneth Ogan, Emory University, Atlanta, GA; Lawrence I. Karsh, The Urology Center of Colorado, Denver, CO; Tracy M. Downs, University of Wisconsin, Madison, WI; Leonard G. Gomella, Thomas Jefferson University, Philadelphia, PA; Ashish M. Kamat and Colin P.N. Dinney, University of Texas MD Anderson Cancer Center; Seth P. Lerner, Baylor College of Medicine, Houston; Yair Lotan, University of Texas Southwestern Medical Center, Dallas; Robert S. Svatek, University of Texas Health Science Center at San Antonio, San Antonio, TX; Trinity J. Bivalacqua, Johns Hopkins School of Medicine, Baltimore, MD; Robert L. Grubb III, Washington University, St Louis, MO; Tracey L. Krupski, University of Virginia, Charlottesville, VA; Michael E. Woods and Matthew I. Milowsky, University of North Carolina, Chapel Hill; Brant A. Inman, Duke University, Durham, NC; Alan Boyd, Alan Boyd Consultants, Cottenham; F. Peter Treasure, Peter Treasure Statistical Services, King's Lynn, United Kingdom; Gillian Gregory, David G. Sawutz, and Nigel R. Parker, FKD Therapies Oy; and Seppo Yla-Herttuala, A.I. Virtanen Institute University of Eastern Finland and Science Service Center and Gene Therapy Unit, Kuopio, Finland.
J Clin Oncol. 2017 Oct 20; 35(30): 3410–3416. Published online 2017 Aug 23. doi: 10.1200/JCO.2017.72.3064