PD-1 Blockade Combined With Chemotherapy Followed by Concurrent Immunoradiotherapy for Locally Advanced SCCA Patients

Summary

Locally Advanced Anal Canal Squamous Carcinoma Patients will be enrolled and given four cycles of neoadjuvant PD-1 antibody toripalimab combined with docetaxol and cisplatin, followed by radiotherapy and two cycles of concurrent toripalimab. Treatment outcomes and toxicities will be evaluated.

Timeline

Start

2021-10-27

Primary completion

2024-06-21

Completion

2024-11-27

Publications

• Results Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.
• Results Amirian ES, Fickey PA Jr, Scheurer ME, Chiao EY. Anal cancer incidence and survival: comparing the greater San-Francisco bay area to other SEER cancer registries. PLoS One. 2013;8(3):e58919. doi: 10.1371/journal.pone.0058919. Epub 2013 Mar 6.
• Results Nigro ND, Vaitkevicius VK, Considine B Jr. Combined therapy for cancer of the anal canal: a preliminary report. 1974. Dis Colon Rectum. 1993 Jul;36(7):709-11. doi: 10.1007/BF02238600. No abstract available.
• Results Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet. 1996 Oct 19;348(9034):1049-54.
• Results Northover J, Glynne-Jones R, Sebag-Montefiore D, James R, Meadows H, Wan S, Jitlal M, Ledermann J. Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer. 2010 Mar 30;102(7):1123-8. doi: 10.1038/sj.bjc.6605605. Epub 2010 Mar 16.
• Results Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, Peiffert D, van Glabbeke M, Pierart M. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol. 1997 May;15(5):2040-9. doi: 10.1200/JCO.1997.15.5.2040.
• Results 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.
• Results Sana S, Khan AU. Clinical trials in the management of anal cancer. Clin Colon Rectal Surg. 2009 May;22(2):115-9. doi: 10.1055/s-0029-1223843.
• Results Chakravarthy AB, Catalano PJ, Martenson JA, Mondschein JK, Wagner H, Mansour EG, Talamonti MS, Benson AB. Long-term follow-up of a Phase II trial of high-dose radiation with concurrent 5-fluorouracil and cisplatin in patients with anal cancer (ECOG E4292). Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e607-13. doi: 10.1016/j.ijrobp.2011.02.042. Epub 2011 Apr 20.
• Results James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, Maughan T, McDonald A, Essapen S, Leslie M, Falk S, Wilson C, Gollins S, Begum R, Ledermann J, Kadalayil L, Sebag-Montefiore D. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 x 2 factorial trial. Lancet Oncol. 2013 May;14(6):516-24. doi: 10.1016/S1470-2045(13)70086-X. Epub 2013 Apr 9.
• Results Olsen JR, Moughan J, Myerson R, Abitbol A, Doncals DE, Johnson D, Schefter TE, Chen Y, Fisher B, Michalski J, Narayan S, Chang A, Crane CH, Kachnic L. Predictors of Radiation Therapy-Related Gastrointestinal Toxicity From Anal Cancer Dose-Painted Intensity Modulated Radiation Therapy: Secondary Analysis of NRG Oncology RTOG 0529. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):400-408. doi: 10.1016/j.ijrobp.2017.02.005. Epub 2017 Feb 13.
• Results Pan YB, Maeda Y, Wilson A, Glynne-Jones R, Vaizey CJ. Late gastrointestinal toxicity after radiotherapy for anal cancer: a systematic literature review. Acta Oncol. 2018 Nov;57(11):1427-1437. doi: 10.1080/0284186X.2018.1503713. Epub 2018 Sep 28.
• Results Hosni A, Han K, Le LW, Ringash J, Brierley J, Wong R, Dinniwell R, Brade A, Dawson LA, Cummings BJ, Krzyzanowska MK, Chen EX, Hedley D, Knox J, Easson AM, Lindsay P, Craig T, Kim J. The ongoing challenge of large anal cancers: prospective long term outcomes of intensity-modulated radiation therapy with concurrent chemotherapy. Oncotarget. 2018 Apr 17;9(29):20439-20450. doi: 10.18632/oncotarget.24926. eCollection 2018 Apr 17.
• Results Russo S, Anker CJ, Abdel-Wahab M, Azad N, Bianchi N, Das P, Dragovic J, Goodman KA, Jones W 3rd, Kennedy T, Kumar R, Lee P, Sharma N, Small W, Suh WW, Jabbour SK. Executive Summary of the American Radium Society Appropriate Use Criteria for Treatment of Anal Cancer. Int J Radiat Oncol Biol Phys. 2019 Nov 1;105(3):591-605. doi: 10.1016/j.ijrobp.2019.06.2544. Epub 2019 Jul 6. No abstract available.
• Results Stewart DB, Gaertner WB, Glasgow SC, Herzig DO, Feingold D, Steele SR; Prepared on Behalf of the Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for Anal Squamous Cell Cancers (Revised 2018). Dis Colon Rectum. 2018 Jul;61(7):755-774. doi: 10.1097/DCR.0000000000001114. No abstract available.
• Results Mullen JT, Rodriguez-Bigas MA, Chang GJ, Barcenas CH, Crane CH, Skibber JM, Feig BW. Results of surgical salvage after failed chemoradiation therapy for epidermoid carcinoma of the anal canal. Ann Surg Oncol. 2007 Feb;14(2):478-83. doi: 10.1245/s10434-006-9221-7. Epub 2006 Nov 14.
• Results Lefevre JH, Parc Y, Kerneis S, Shields C, Touboul E, Chaouat M, Tiret E. Abdomino-perineal resection for anal cancer: impact of a vertical rectus abdominis myocutaneus flap on survival, recurrence, morbidity, and wound healing. Ann Surg. 2009 Nov;250(5):707-11. doi: 10.1097/SLA.0b013e3181bce334.
• Results Ben-Josef E, Moughan J, Ajani JA, Flam M, Gunderson L, Pollock J, Myerson R, Anne R, Rosenthal SA, Willett C. Impact of overall treatment time on survival and local control in patients with anal cancer: a pooled data analysis of Radiation Therapy Oncology Group trials 87-04 and 98-11. J Clin Oncol. 2010 Dec 1;28(34):5061-6. doi: 10.1200/JCO.2010.29.1351. Epub 2010 Oct 18.
• Results Nilsson PJ, Svensson C, Goldman S, Ljungqvist O, Glimelius B. Epidermoid anal cancer: a review of a population-based series of 308 consecutive patients treated according to prospective protocols. Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):92-102. doi: 10.1016/j.ijrobp.2004.03.034.
• Results Moureau-Zabotto L, Viret F, Giovaninni M, Lelong B, Bories E, Delpero JR, Pesenti C, Caillol F, de Chaisemartin C, Minsat M, Monges G, Sarran A, Resbeut M. Is neoadjuvant chemotherapy prior to radio-chemotherapy beneficial in T4 anal carcinoma? J Surg Oncol. 2011 Jul 1;104(1):66-71. doi: 10.1002/jso.21866. Epub 2011 Jan 15.
• Results Ott PA, Piha-Paul SA, Munster P, Pishvaian MJ, van Brummelen EMJ, Cohen RB, Gomez-Roca C, Ejadi S, Stein M, Chan E, Simonelli M, Morosky A, Saraf S, Emancipator K, Koshiji M, Bennouna J. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol. 2017 May 1;28(5):1036-1041. doi: 10.1093/annonc/mdx029.
• Results Shahjehan F, Kamatham S, Ritter A, Kasi PM. Dramatic response to modified docetaxel, cisplatin, and fluorouracil chemotherapy after immunotherapy in a patient with refractory metastatic anal cancer. Clin Case Rep. 2019 Aug 6;7(9):1729-1734. doi: 10.1002/ccr3.2333. eCollection 2019 Sep.
• Results Morris VK, Salem ME, Nimeiri H, Iqbal S, Singh P, Ciombor K, Polite B, Deming D, Chan E, Wade JL, Xiao L, Bekaii-Saab T, Vence L, Blando J, Mahvash A, Foo WC, Ohaji C, Pasia M, Bland G, Ohinata A, Rogers J, Mehdizadeh A, Banks K, Lanman R, Wolff RA, Streicher H, Allison J, Sharma P, Eng C. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017 Apr;18(4):446-453. doi: 10.1016/S1470-2045(17)30104-3. Epub 2017 Feb 18.
• Results Rao S, Sclafani F, Eng C, Adams RA, Guren MG, Sebag-Montefiore D, Benson A, Bryant A, Peckitt C, Segelov E, Roy A, Seymour MT, Welch J, Saunders MP, Muirhead R, O'Dwyer P, Bridgewater J, Bhide S, Glynne-Jones R, Arnold D, Cunningham D. International Rare Cancers Initiative Multicenter Randomized Phase II Trial of Cisplatin and Fluorouracil Versus Carboplatin and Paclitaxel in Advanced Anal Cancer: InterAAct. J Clin Oncol. 2020 Aug 1;38(22):2510-2518. doi: 10.1200/JCO.19.03266. Epub 2020 Jun 12.

Drugs

Indications