Cabozantinib in Patients With Advanced Penile Squamous Cell Carcinoma (PSCC) (CaboPen)

Summary

Cabozantinib in patients with advanced penile squamous cell carcinoma (PSCC): an open-label, single-center, phase 2, single-arm trial (CaboPen)

Timeline

Start

2019-08-01

Primary completion

2022-06-01

Completion

2022-09-01

Publications

• Background Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29. doi: 10.3322/caac.20138. Epub 2012 Jan 4.
• Background Barnholtz-Sloan JS, Maldonado JL, Pow-sang J, Giuliano AR. Incidence trends in primary malignant penile cancer. Urol Oncol. 2007 Sep-Oct;25(5):361-7. doi: 10.1016/j.urolonc.2006.08.029.
• Background Ornellas AA. Management of penile cancer. J Surg Oncol. 2008 Mar 1;97(3):199-200. doi: 10.1002/jso.20893. No abstract available.
• Background Misra S, Chaturvedi A, Misra NC. Penile carcinoma: a challenge for the developing world. Lancet Oncol. 2004 Apr;5(4):240-7. doi: 10.1016/S1470-2045(04)01427-5.
• Background Heideman DA, Waterboer T, Pawlita M, Delis-van Diemen P, Nindl I, Leijte JA, Bonfrer JM, Horenblas S, Meijer CJ, Snijders PJ. Human papillomavirus-16 is the predominant type etiologically involved in penile squamous cell carcinoma. J Clin Oncol. 2007 Oct 10;25(29):4550-6. doi: 10.1200/JCO.2007.12.3182.
• Background Li D, Han Z, Liu J, Zhang X, Ren J, Yan L, Liu H, Xu Z. Upregulation of nucleus HDGF predicts poor prognostic outcome in patients with penile squamous cell carcinoma bypass VEGF-A and Ki-67. Med Oncol. 2013 Dec;30(4):702. doi: 10.1007/s12032-013-0702-9. Epub 2013 Sep 3.
• Background Zhu Y, Li H, Yao XD, Zhang SL, Zhang HL, Shi GH, Yang LF, Yang ZY, Wang CF, Ye DW. Feasibility and activity of sorafenib and sunitinib in advanced penile cancer: a preliminary report. Urol Int. 2010;85(3):334-40. doi: 10.1159/000315432. Epub 2010 Oct 27.
• Background Bleeker MC, Heideman DA, Snijders PJ, Horenblas S, Dillner J, Meijer CJ. Penile cancer: epidemiology, pathogenesis and prevention. World J Urol. 2009 Apr;27(2):141-50. doi: 10.1007/s00345-008-0302-z. Epub 2008 Jul 8.
• Background Bezerra AL, Lopes A, Santiago GH, Ribeiro KC, Latorre MR, Villa LL. Human papillomavirus as a prognostic factor in carcinoma of the penis: analysis of 82 patients treated with amputation and bilateral lymphadenectomy. Cancer. 2001 Jun 15;91(12):2315-21.
• Background Backes DM, Kurman RJ, Pimenta JM, Smith JS. Systematic review of human papillomavirus prevalence in invasive penile cancer. Cancer Causes Control. 2009 May;20(4):449-57. doi: 10.1007/s10552-008-9276-9. Epub 2008 Dec 11.
• Background Gregoire L, Cubilla AL, Reuter VE, Haas GP, Lancaster WD. Preferential association of human papillomavirus with high-grade histologic variants of penile-invasive squamous cell carcinoma. J Natl Cancer Inst. 1995 Nov 15;87(22):1705-9. doi: 10.1093/jnci/87.22.1705.
• Background Miralles-Guri C, Bruni L, Cubilla AL, Castellsague X, Bosch FX, de Sanjose S. Human papillomavirus prevalence and type distribution in penile carcinoma. J Clin Pathol. 2009 Oct;62(10):870-8. doi: 10.1136/jcp.2008.063149. Epub 2009 Aug 25.
• Background Rubin MA, Kleter B, Zhou M, Ayala G, Cubilla AL, Quint WG, Pirog EC. Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol. 2001 Oct;159(4):1211-8. doi: 10.1016/S0002-9440(10)62506-0.
• Background Mannweiler S, Sygulla S, Beham-Schmid C, Razmara Y, Pummer K, Regauer S. Penile carcinogenesis in a low-incidence area: a clinicopathologic and molecular analysis of 115 invasive carcinomas with special emphasis on chronic inflammatory skin diseases. Am J Surg Pathol. 2011 Jul;35(7):998-1006. doi: 10.1097/PAS.0b013e3182147e59.
• Background Castellsague X, Bosch FX, Munoz N, Meijer CJ, Shah KV, de Sanjose S, Eluf-Neto J, Ngelangel CA, Chichareon S, Smith JS, Herrero R, Moreno V, Franceschi S; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med. 2002 Apr 11;346(15):1105-12. doi: 10.1056/NEJMoa011688.
• Background Backes DM, Bleeker MC, Meijer CJ, Hudgens MG, Agot K, Bailey RC, Ndinya-Achola JO, Hayombe J, Hogewoning CJ, Moses S, Snijders PJ, Smith JS. Male circumcision is associated with a lower prevalence of human papillomavirus-associated penile lesions among Kenyan men. Int J Cancer. 2012 Apr 15;130(8):1888-97. doi: 10.1002/ijc.26196. Epub 2011 Aug 2.
• Background Barroso LF 2nd, Wilkin T. Human papillomavirus vaccination in males: the state of the science. Curr Infect Dis Rep. 2011 Apr;13(2):175-81. doi: 10.1007/s11908-010-0163-7.
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• Background Daling JR, Madeleine MM, Johnson LG, Schwartz SM, Shera KA, Wurscher MA, Carter JJ, Porter PL, Galloway DA, McDougall JK, Krieger JN. Penile cancer: importance of circumcision, human papillomavirus and smoking in in situ and invasive disease. Int J Cancer. 2005 Sep 10;116(4):606-16. doi: 10.1002/ijc.21009.
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• Background Marconnet L, Rigaud J, Bouchot O. Long-term followup of penile carcinoma with high risk for lymph node invasion treated with inguinal lymphadenectomy. J Urol. 2010 Jun;183(6):2227-32. doi: 10.1016/j.juro.2010.02.025.
• Background Protzel C, Alcaraz A, Horenblas S, Pizzocaro G, Zlotta A, Hakenberg OW. Lymphadenectomy in the surgical management of penile cancer. Eur Urol. 2009 May;55(5):1075-88. doi: 10.1016/j.eururo.2009.02.021. Epub 2009 Feb 23.
• Background Heyns CF, Fleshner N, Sangar V, Schlenker B, Yuvaraja TB, van Poppel H. Management of the lymph nodes in penile cancer. Urology. 2010 Aug;76(2 Suppl 1):S43-57. doi: 10.1016/j.urology.2010.03.001.
• Background Pompeo AC. Extended lymphadenectomy in penile cancer. Can J Urol. 2005 Feb;12 Suppl 1:30-6; discussion 97-8.
• Background Kroon BK, Horenblas S, Lont AP, Tanis PJ, Gallee MP, Nieweg OE. Patients with penile carcinoma benefit from immediate resection of clinically occult lymph node metastases. J Urol. 2005 Mar;173(3):816-9. doi: 10.1097/01.ju.0000154565.37397.4d.
• Background Lont AP, Kroon BK, Gallee MP, van Tinteren H, Moonen LM, Horenblas S. Pelvic lymph node dissection for penile carcinoma: extent of inguinal lymph node involvement as an indicator for pelvic lymph node involvement and survival. J Urol. 2007 Mar;177(3):947-52; discussion 952. doi: 10.1016/j.juro.2006.10.060.
• Background Ornellas AA, Kinchin EW, Nobrega BL, Wisnescky A, Koifman N, Quirino R. Surgical treatment of invasive squamous cell carcinoma of the penis: Brazilian National Cancer Institute long-term experience. J Surg Oncol. 2008 May 1;97(6):487-95. doi: 10.1002/jso.20980.
• Background Spiess PE, Izawa JI, Bassett R, Kedar D, Busby JE, Wong F, Eddings T, Tamboli P, Pettaway CA. Preoperative lymphoscintigraphy and dynamic sentinel node biopsy for staging penile cancer: results with pathological correlation. J Urol. 2007 Jun;177(6):2157-61. doi: 10.1016/j.juro.2007.01.125.
• Background Izawa J, Kedar D, Wong F, Pettaway CA. Sentinel lymph node biopsy in penile cancer: evolution and insights. Can J Urol. 2005 Feb;12 Suppl 1:24-9.
• Background Hungerhuber E, Schlenker B, Frimberger D, Linke R, Karl A, Stief CG, Schneede P. Lymphoscintigraphy in penile cancer: limited value of sentinel node biopsy in patients with clinically suspicious lymph nodes. World J Urol. 2006 Aug;24(3):319-24. doi: 10.1007/s00345-006-0073-3. Epub 2006 Apr 11.
• Background Neto AS, Tobias-Machado M, Ficarra V, Wroclawski ML, Amarante RD, Pompeo AC, Del Giglio A. Dynamic sentinel node biopsy for inguinal lymph node staging in patients with penile cancer: a systematic review and cumulative analysis of the literature. Ann Surg Oncol. 2011 Jul;18(7):2026-34. doi: 10.1245/s10434-010-1546-6. Epub 2011 Feb 10.
• Background Graafland NM, Valdes Olmos RA, Meinhardt W, Bex A, van der Poel HG, van Boven HH, Nieweg OE, Horenblas S. Nodal staging in penile carcinoma by dynamic sentinel node biopsy after previous therapeutic primary tumour resection. Eur Urol. 2010 Nov;58(5):748-51. doi: 10.1016/j.eururo.2010.06.036. Epub 2010 Jul 12.
• Background Pettaway CA, Pisters LL, Dinney CP, Jularbal F, Swanson DA, von Eschenbach AC, Ayala A. Sentinel lymph node dissection for penile carcinoma: the M. D. Anderson Cancer Center experience. J Urol. 1995 Dec;154(6):1999-2003.
• Background Pizzocaro G, Algaba F, Horenblas S, Solsona E, Tana S, Van Der Poel H, Watkin NA; European Association of Urology (EAU) Guidelines Group on Penile Cancer. EAU penile cancer guidelines 2009. Eur Urol. 2010 Jun;57(6):1002-12. doi: 10.1016/j.eururo.2010.01.039. Epub 2010 Feb 4.
• Background Gagliano RG, Blumenstein BA, Crawford ED, Stephens RL, Coltman CA Jr, Costanzi JJ. cis-Diamminedichloroplatinum in the treatment of advanced epidermoid carcinoma of the penis: a Southwest Oncology Group Study. J Urol. 1989 Jan;141(1):66-7. doi: 10.1016/s0022-5347(17)40590-8.
• Background Leijte JA, Kirrander P, Antonini N, Windahl T, Horenblas S. Recurrence patterns of squamous cell carcinoma of the penis: recommendations for follow-up based on a two-centre analysis of 700 patients. Eur Urol. 2008 Jul;54(1):161-8. doi: 10.1016/j.eururo.2008.04.016. Epub 2008 Apr 15.
• Background Culkin DJ, Beer TM. Advanced penile carcinoma. J Urol. 2003 Aug;170(2 Pt 1):359-65. doi: 10.1097/01.ju.0000062829.43654.5e.
• Background Pizzocaro G, Piva L. Adjuvant and neoadjuvant vincristine, bleomycin, and methotrexate for inguinal metastases from squamous cell carcinoma of the penis. Acta Oncol. 1988;27(6b):823-4. doi: 10.3109/02841868809094366.
• Background Leijte JA, Kerst JM, Bais E, Antonini N, Horenblas S. Neoadjuvant chemotherapy in advanced penile carcinoma. Eur Urol. 2007 Aug;52(2):488-94. doi: 10.1016/j.eururo.2007.02.006. Epub 2007 Feb 14.
• Background Hakenberg OW, Nippgen JB, Froehner M, Zastrow S, Wirth MP. Cisplatin, methotrexate and bleomycin for treating advanced penile carcinoma. BJU Int. 2006 Dec;98(6):1225-7. doi: 10.1111/j.1464-410X.2006.06496.x.
• Background Bermejo C, Busby JE, Spiess PE, Heller L, Pagliaro LC, Pettaway CA. Neoadjuvant chemotherapy followed by aggressive surgical consolidation for metastatic penile squamous cell carcinoma. J Urol. 2007 Apr;177(4):1335-8. doi: 10.1016/j.juro.2006.11.038.
• Background Pagliaro LC, Williams DL, Daliani D, Williams MB, Osai W, Kincaid M, Wen S, Thall PF, Pettaway CA. Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study. J Clin Oncol. 2010 Aug 20;28(24):3851-7. doi: 10.1200/JCO.2010.29.5477. Epub 2010 Jul 12.
• Background Graafland NM, Valdes Olmos RA, Teertstra HJ, Kerst JM, Bergman AM, Horenblas S. 18F-FDG PET/CT for monitoring induction chemotherapy in patients with primary inoperable penile carcinoma: first clinical results. Eur J Nucl Med Mol Imaging. 2010 Aug;37(8):1474-80. doi: 10.1007/s00259-010-1434-0. Epub 2010 Mar 27.
• Background Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1695-704. doi: 10.1056/NEJMoa071028.
• Background Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1705-15. doi: 10.1056/NEJMoa070956.
• Background Hitt R, Lopez-Pousa A, Martinez-Trufero J, Escrig V, Carles J, Rizo A, Isla D, Vega ME, Marti JL, Lobo F, Pastor P, Valenti V, Belon J, Sanchez MA, Chaib C, Pallares C, Anton A, Cervantes A, Paz-Ares L, Cortes-Funes H. Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer. J Clin Oncol. 2005 Dec 1;23(34):8636-45. doi: 10.1200/JCO.2004.00.1990. Epub 2005 Nov 7.
• Background Maiche AG. Adjuvant treatment using bleomycin in squamous cell carcinoma of penis: study of 19 cases. Br J Urol. 1983 Oct;55(5):542-4. doi: 10.1111/j.1464-410x.1983.tb03366.x.
• Background Protzel C, Ruppin S, Milerski S, Klebingat KJ, Hakenberg OW. [The current state of the art of chemotherapy of penile cancer: results of a nationwide survey of German clinics]. Urologe A. 2009 Dec;48(12):1495-8. doi: 10.1007/s00120-009-2108-z. German.
• Background Corral DA, Sella A, Pettaway CA, Amato RJ, Jones DM, Ellerhorst J. Combination chemotherapy for metastatic or locally advanced genitourinary squamous cell carcinoma: a phase II study of methotrexate, cisplatin and bleomycin. J Urol. 1998 Nov;160(5):1770-4.
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• Background Pettaway CA, Pagliaro L, Theodore C, Haas G. Treatment of visceral, unresectable, or bulky/unresectable regional metastases of penile cancer. Urology. 2010 Aug;76(2 Suppl 1):S58-65. doi: 10.1016/j.urology.2010.03.082.
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Drugs

Indications