Prior Axitinib as a Determinant of Outcome of Renal Surgery

Summary

This is a single arm phase II study of axitinib in patients with clear cell renal cell carcinoma (RCC) with strong indications for partial nephrectomy (PN) for whom PN is not currently possible due to anatomic considerations and residual renal function concerns. Evaluation of tumor downsizing will be performed including changes of tumor complexity by nephrometry score. A total of 50 participants will be enrolled. It is hypothesized that pretreatment with axitinib will be safe and improve the feasibility of complex nephron sparing surgery in select patients with localized clear cell RCC and imperative indications for partial nephrectomy.

Timeline

Start

2018-03-05

Primary completion

2026-03-04

Completion

2026-03-04

Publications

• Background Rini BI, Campbell SC, Escudier B. Renal cell carcinoma. Lancet. 2009 Mar 28;373(9669):1119-32. doi: 10.1016/S0140-6736(09)60229-4. Epub 2009 Mar 5.
• Background Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29. doi: 10.3322/caac.21208. Epub 2014 Jan 7.
• Background Russo P. End stage and chronic kidney disease: associations with renal cancer. Front Oncol. 2012 Apr 2;2:28. doi: 10.3389/fonc.2012.00028. eCollection 2012.
• Background Kane CJ, Mallin K, Ritchey J, Cooperberg MR, Carroll PR. Renal cell cancer stage migration: analysis of the National Cancer Data Base. Cancer. 2008 Jul 1;113(1):78-83. doi: 10.1002/cncr.23518.
• Background Lee HJ, Liss MA, Derweesh IH. Outcomes of partial nephrectomy for clinical T1b and T2 renal tumors. Curr Opin Urol. 2014 Sep;24(5):448-52. doi: 10.1097/MOU.0000000000000081.
• Background Brandao LF, Zargar H, Autorino R, Akca O, Laydner H, Samarasekera D, Krishnan J, Haber GP, Stein RJ, Kaouk JH. Robot-assisted partial nephrectomy for >/= 7 cm renal masses: a comparative outcome analysis. Urology. 2014 Sep;84(3):602-8. doi: 10.1016/j.urology.2014.04.015. Epub 2014 Jun 12.
• Background Karellas ME, O'Brien MF, Jang TL, Bernstein M, Russo P. Partial nephrectomy for selected renal cortical tumours of >/= 7 cm. BJU Int. 2010 Nov;106(10):1484-7. doi: 10.1111/j.1464-410X.2010.09405.x.
• Background Breau RH, Crispen PL, Jimenez RE, Lohse CM, Blute ML, Leibovich BC. Outcome of stage T2 or greater renal cell cancer treated with partial nephrectomy. J Urol. 2010 Mar;183(3):903-8. doi: 10.1016/j.juro.2009.11.037. Epub 2010 Jan 18.
• Background Long CJ, Canter DJ, Kutikov A, Li T, Simhan J, Smaldone M, Teper E, Viterbo R, Boorjian SA, Chen DY, Greenberg RE, Uzzo RG. Partial nephrectomy for renal masses >/= 7 cm: technical, oncological and functional outcomes. BJU Int. 2012 May;109(10):1450-6. doi: 10.1111/j.1464-410X.2011.10608.x. Epub 2012 Jan 5.
• Background Kopp RP, Mehrazin R, Palazzi KL, Liss MA, Jabaji R, Mirheydar HS, Lee HJ, Patel N, Elkhoury F, Patterson AL, Derweesh IH. Survival outcomes after radical and partial nephrectomy for clinical T2 renal tumours categorised by R.E.N.A.L. nephrometry score. BJU Int. 2014 Nov;114(5):708-18. doi: 10.1111/bju.12580. Epub 2014 Oct 3.
• Background Alanee S, Nutt M, Moore A, Holland B, Dynda D, Wilber A, El-Zawahry A. Partial nephrectomy for T2 renal masses: contemporary trends and oncologic efficacy. Int Urol Nephrol. 2015 Jun;47(6):945-50. doi: 10.1007/s11255-015-0975-3. Epub 2015 Apr 12.
• Background Kopp RP, Liss MA, Mehrazin R, Wang S, Lee HJ, Jabaji R, Mirheydar HS, Gillis K, Patel N, Palazzi KL, Wan JY, Patterson AL, Derweesh IH. Analysis of Renal Functional Outcomes After Radical or Partial Nephrectomy for Renal Masses >/=7 cm Using the RENAL Score. Urology. 2015 Aug;86(2):312-9. doi: 10.1016/j.urology.2015.02.067. Epub 2015 Jul 16.
• Background Randall JM, Millard F, Kurzrock R. Molecular aberrations, targeted therapy, and renal cell carcinoma: current state-of-the-art. Cancer Metastasis Rev. 2014 Dec;33(4):1109-24. doi: 10.1007/s10555-014-9533-1.
• Background Thomas AA, Rini BI, Lane BR, Garcia J, Dreicer R, Klein EA, Novick AC, Campbell SC. Response of the primary tumor to neoadjuvant sunitinib in patients with advanced renal cell carcinoma. J Urol. 2009 Feb;181(2):518-23; discussion 523. doi: 10.1016/j.juro.2008.10.001. Epub 2008 Dec 18.
• Background Cowey CL, Amin C, Pruthi RS, Wallen EM, Nielsen ME, Grigson G, Watkins C, Nance KV, Crane J, Jalkut M, Moore DT, Kim WY, Godley PA, Whang YE, Fielding JR, Rathmell WK. Neoadjuvant clinical trial with sorafenib for patients with stage II or higher renal cell carcinoma. J Clin Oncol. 2010 Mar 20;28(9):1502-7. doi: 10.1200/JCO.2009.24.7759. Epub 2010 Feb 16.
• Background Silberstein JL, Millard F, Mehrazin R, Kopp R, Bazzi W, DiBlasio CJ, Patterson AL, Downs TM, Yunus F, Kane CJ, Derweesh IH. Feasibility and efficacy of neoadjuvant sunitinib before nephron-sparing surgery. BJU Int. 2010 Nov;106(9):1270-6. doi: 10.1111/j.1464-410X.2010.09357.x.
• Background Rini BI, Plimack ER, Takagi T, Elson P, Wood LS, Dreicer R, Gilligan T, Garcia J, Zhang Z, Kaouk J, Krishnamurthi V, Stephenson AJ, Fergany A, Klein EA, Uzzo RG, Chen DY, Campbell SC. A Phase II Study of Pazopanib in Patients with Localized Renal Cell Carcinoma to Optimize Preservation of Renal Parenchyma. J Urol. 2015 Aug;194(2):297-303. doi: 10.1016/j.juro.2015.03.096. Epub 2015 Mar 23.
• Background Karam JA, Devine CE, Urbauer DL, Lozano M, Maity T, Ahrar K, Tamboli P, Tannir NM, Wood CG. Phase 2 trial of neoadjuvant axitinib in patients with locally advanced nonmetastatic clear cell renal cell carcinoma. Eur Urol. 2014 Nov;66(5):874-80. doi: 10.1016/j.eururo.2014.01.035. Epub 2014 Feb 7.
• Background Lane BR, Derweesh IH, Kim HL, O'Malley R, Klink J, Ercole CE, Palazzi KL, Thomas AA, Rini BI, Campbell SC. Presurgical sunitinib reduces tumor size and may facilitate partial nephrectomy in patients with renal cell carcinoma. Urol Oncol. 2015 Mar;33(3):112.e15-21. doi: 10.1016/j.urolonc.2014.11.009. Epub 2014 Dec 19.
• Background Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. doi: 10.1016/S0140-6736(11)61613-9. Epub 2011 Nov 4.
• Background Tzogani K, Skibeli V, Westgaard I, Dalhus M, Thoresen H, Slot KB, Damkier P, Hofland K, Borregaard J, Ersboll J, Salmonson T, Pieters R, Sylvester R, Mickisch G, Bergh J, Pignatti F. The European Medicines Agency approval of axitinib (Inlyta) for the treatment of advanced renal cell carcinoma after failure of prior treatment with sunitinib or a cytokine: summary of the scientific assessment of the committee for medicinal products for human use. Oncologist. 2015 Feb;20(2):196-201. doi: 10.1634/theoncologist.2014-0177. Epub 2015 Jan 23.
• Background Lane BR, Demirjian S, Derweesh IH, Takagi T, Zhang Z, Velet L, Ercole CE, Fergany AF, Campbell SC. Survival and Functional Stability in Chronic Kidney Disease Due to Surgical Removal of Nephrons: Importance of the New Baseline Glomerular Filtration Rate. Eur Urol. 2015 Dec;68(6):996-1003. doi: 10.1016/j.eururo.2015.04.043. Epub 2015 May 23.
• Background Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
• Background van der Veldt AA, Meijerink MR, van den Eertwegh AJ, Bex A, de Gast G, Haanen JB, Boven E. Sunitinib for treatment of advanced renal cell cancer: primary tumor response. Clin Cancer Res. 2008 Apr 15;14(8):2431-6. doi: 10.1158/1078-0432.CCR-07-4089.

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Indications