Study of Pomalidomide in Anal Cancer Precursors

Summary

This is a single centre open label phase II trial to determine the antitumor efficacy of the oral immunomodulatory agent pomalidomide in persistent human papillomavirus (HPV) -associated high grade squamous intra-epithelial lesions (HSIL) in patients with and without human immunodeficiency virus (HIV) infection.

Timeline

Start

2017-06-14

Primary completion

2019-03-31

Completion

2022-12-31

Publications

• Background Munoz N, Castellsague X, Berrington de Gonzalez A, Gissmann L. Chapter 1: HPV in the etiology of human cancer. Vaccine. 2006 Aug 31;24 Suppl 3:S3/1-10. doi: 10.1016/j.vaccine.2006.05.115. Epub 2006 Jun 23.
• Background Parkin DM, Bray F. Chapter 2: The burden of HPV-related cancers. Vaccine. 2006 Aug 31;24 Suppl 3:S3/11-25. doi: 10.1016/j.vaccine.2006.05.111.
• Background World Health Organization International Agency for Reseach on Cancer. IARC Monograph on the Evaluation of Carcinogenic Risks to Humans: Volume 90, Human Papillomavirus. World Health Organization, Geneva 2007.
• Background Machalek DA, Poynten M, Jin F, Fairley CK, Farnsworth A, Garland SM, Hillman RJ, Petoumenos K, Roberts J, Tabrizi SN, Templeton DJ, Grulich AE. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012 May;13(5):487-500. doi: 10.1016/S1470-2045(12)70080-3. Epub 2012 Mar 23.
• Background Palefsky JM. Anal cancer prevention in HIV-positive men and women. Curr Opin Oncol. 2009 Sep;21(5):433-8. doi: 10.1097/CCO.0b013e32832f511a.
• Background Grulich AE, Poynten IM, Machalek DA, Jin F, Templeton DJ, Hillman RJ. The epidemiology of anal cancer. Sex Health. 2012 Dec;9(6):504-8. doi: 10.1071/SH12070.
• Background Petoumenos K, van Leuwen MT, Vajdic CM, Woolley I, Chuah J, Templeton DJ, Grulich AE, Law MG; Australian HIV Observational Database. Cancer, immunodeficiency and antiretroviral treatment: results from the Australian HIV Observational Database (AHOD). HIV Med. 2013 Feb;14(2):77-84. doi: 10.1111/j.1468-1293.2012.01038.x. Epub 2012 Aug 30.
• Background Yarchoan R, Tosato G, Little RF. Therapy insight: AIDS-related malignancies--the influence of antiviral therapy on pathogenesis and management. Nat Clin Pract Oncol. 2005 Aug;2(8):406-15; quiz 423. doi: 10.1038/ncponc0253.
• Background Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, Willett C. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008 Apr 23;299(16):1914-21. doi: 10.1001/jama.299.16.1914.
• Background Moscicki AB, Schiffman M, Kjaer S, Villa LL. Chapter 5: Updating the natural history of HPV and anogenital cancer. Vaccine. 2006 Aug 31;24 Suppl 3:S3/42-51. doi: 10.1016/j.vaccine.2006.06.018. Epub 2006 Jun 23.
• Background Tong WW, Shepherd K, Garland S, Meagher A, Templeton DJ, Fairley CK, Jin F, Poynten IM, Zaunders J, Hillman RJ, Grulich AE, Kelleher AD, Carr A; Study of the Prevention of Anal Cancer (SPANC) team. Human papillomavirus 16-specific T-cell responses and spontaneous regression of anal high-grade squamous intraepithelial lesions. J Infect Dis. 2015 Feb 1;211(3):405-15. doi: 10.1093/infdis/jiu461. Epub 2014 Aug 19.
• Background Quach H, Ritchie D, Stewart AK, Neeson P, Harrison S, Smyth MJ, Prince HM. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia. 2010 Jan;24(1):22-32. doi: 10.1038/leu.2009.236. Epub 2009 Nov 12.
• Background Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, Yamaguchi Y, Handa H. Identification of a primary target of thalidomide teratogenicity. Science. 2010 Mar 12;327(5971):1345-50. doi: 10.1126/science.1177319.
• Background Gorgun G, Calabrese E, Soydan E, Hideshima T, Perrone G, Bandi M, Cirstea D, Santo L, Hu Y, Tai YT, Nahar S, Mimura N, Fabre C, Raje N, Munshi N, Richardson P, Anderson KC. Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood. 2010 Oct 28;116(17):3227-37. doi: 10.1182/blood-2010-04-279893. Epub 2010 Jul 22.
• Background Lentzsch S, LeBlanc R, Podar K, Davies F, Lin B, Hideshima T, Catley L, Stirling DI, Anderson KC. Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo. Leukemia. 2003 Jan;17(1):41-4. doi: 10.1038/sj.leu.2402745.
• Background Reddy N, Hernandez-Ilizaliturri FJ, Deeb G, Roth M, Vaughn M, Knight J, Wallace P, Czuczman MS. Immunomodulatory drugs stimulate natural killer-cell function, alter cytokine production by dendritic cells, and inhibit angiogenesis enhancing the anti-tumour activity of rituximab in vivo. Br J Haematol. 2008 Jan;140(1):36-45. doi: 10.1111/j.1365-2141.2007.06841.x. Epub 2007 Nov 9.
• Background Verhelle D, Corral LG, Wong K, Mueller JH, Moutouh-de Parseval L, Jensen-Pergakes K, Schafer PH, Chen R, Glezer E, Ferguson GD, Lopez-Girona A, Muller GW, Brady HA, Chan KW. Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res. 2007 Jan 15;67(2):746-55. doi: 10.1158/0008-5472.CAN-06-2317.
• Background Zhu D, Corral LG, Fleming YW, Stein B. Immunomodulatory drugs Revlimid (lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation. Cancer Immunol Immunother. 2008 Dec;57(12):1849-59. doi: 10.1007/s00262-008-0512-7. Epub 2008 Apr 8.
• Background Shalapour S, Zelmer A, Pfau M, Moderegger E, Costa-Blechschmidt C, van Landeghem FK, Taube T, Fichtner I, Buhrer C, Henze G, Seeger K, Wellmann S. The thalidomide analogue, CC-4047, induces apoptosis signaling and growth arrest in childhood acute lymphoblastic leukemia cells in vitro and in vivo. Clin Cancer Res. 2006 Sep 15;12(18):5526-32. doi: 10.1158/1078-0432.CCR-06-0719.
• Background Escoubet-Lozach L, Lin IL, Jensen-Pergakes K, Brady HA, Gandhi AK, Schafer PH, Muller GW, Worland PJ, Chan KW, Verhelle D. Pomalidomide and lenalidomide induce p21 WAF-1 expression in both lymphoma and multiple myeloma through a LSD1-mediated epigenetic mechanism. Cancer Res. 2009 Sep 15;69(18):7347-56. doi: 10.1158/0008-5472.CAN-08-4898. Epub 2009 Sep 8.
• Background Pal R, Monaghan SA, Hassett AC, Mapara MY, Schafer P, Roodman GD, Ragni MV, Moscinski L, List A, Lentzsch S. Immunomodulatory derivatives induce PU.1 down-regulation, myeloid maturation arrest, and neutropenia. Blood. 2010 Jan 21;115(3):605-14. doi: 10.1182/blood-2009-05-221077. Epub 2009 Nov 25.
• Background Polizzotto MN, Sereti I, Uldrick TS, et al. Pomalidomide induces expansion of activated and central memory CD4 and CD8 T-cells in vivo in patients with and without HIV infection. American Society of Hematology Annual Meeting, San Francisco 2014.
• Background Polizzotto MN, Uldrick TS, Wyvill KM, Aleman K, Peer CJ, Bevans M, Sereti I, Maldarelli F, Whitby D, Marshall V, Goncalves PH, Khetani V, Figg WD, Steinberg SM, Zeldis JB, Yarchoan R. Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study. J Clin Oncol. 2016 Dec;34(34):4125-4131. doi: 10.1200/JCO.2016.69.3812. Epub 2016 Oct 31.
• Background Machalek DA, Grulich AE, Hillman RJ, Jin F, Templeton DJ, Tabrizi SN, Garland SM, Prestage G, McCaffery K, Howard K, Tong W, Fairley CK, Roberts J, Farnsworth A, Poynten IM; SPANC Study Team. The Study of the Prevention of Anal Cancer (SPANC): design and methods of a three-year prospective cohort study. BMC Public Health. 2013 Oct 9;13:946. doi: 10.1186/1471-2458-13-946.
• Background Richel O, de Vries HJ, van Noesel CJ, Dijkgraaf MG, Prins JM. Comparison of imiquimod, topical fluorouracil, and electrocautery for the treatment of anal intraepithelial neoplasia in HIV-positive men who have sex with men: an open-label, randomised controlled trial. Lancet Oncol. 2013 Apr;14(4):346-53. doi: 10.1016/S1470-2045(13)70067-6. Epub 2013 Mar 15.
• Background POMALYST® (pomalidomide) capsules Product Information. Department of Health Therapeutic Goods Administration (TGA) April 2016. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf accessed 23 Nov 2016.

Drugs

Indications