The Quarterback Trial: Reduced Dose Radiotherapy for HPV+ Oropharynx Cancer

Summary

This trial aims to directly compare a reduced radiation dose to the standard of care in HPVOPC for non-inferiority, thus allowing for direct comparison of outcomes between the two groups. The study hypothesis is that LRC and PFS at 3 years for reduced dose CRT are non-inferior to standard dose CRT.

Timeline

Start

2012-09-01

Primary completion

2020-04-01

Completion

2035-05-01

Publications

• Background Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011 Nov 10;29(32):4294-301. doi: 10.1200/JCO.2011.36.4596. Epub 2011 Oct 3.
• Background Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol. 2008 Feb 1;26(4):612-9. doi: 10.1200/JCO.2007.14.1713.
• Background Nasman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G, Ahrlund-Richter S, Marklund L, Romanitan M, Lindquist D, Ramqvist T, Lindholm J, Sparen P, Ye W, Dahlstrand H, Munck-Wikland E, Dalianis T. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer. 2009 Jul 15;125(2):362-6. doi: 10.1002/ijc.24339.
• Background Andl T, Kahn T, Pfuhl A, Nicola T, Erber R, Conradt C, Klein W, Helbig M, Dietz A, Weidauer H, Bosch FX. Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control. Cancer Res. 1998 Jan 1;58(1):5-13.
• Background Munger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M, Grace M, Huh K. Mechanisms of human papillomavirus-induced oncogenesis. J Virol. 2004 Nov;78(21):11451-60. doi: 10.1128/JVI.78.21.11451-11460.2004. No abstract available.
• Background Psyrri A, DeFilippis RA, Edwards AP, Yates KE, Manuelidis L, DiMaio D. Role of the retinoblastoma pathway in senescence triggered by repression of the human papillomavirus E7 protein in cervical carcinoma cells. Cancer Res. 2004 May 1;64(9):3079-86. doi: 10.1158/0008-5472.can-03-3739.
• Background Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J, Sasaki C, Joe J, Camp RL, Rimm DL, Psyrri A. Molecular classification identifies a subset of human papillomavirus--associated oropharyngeal cancers with favorable prognosis. J Clin Oncol. 2006 Feb 10;24(5):736-47. doi: 10.1200/JCO.2004.00.3335. Epub 2006 Jan 9.
• Background Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.
• Background Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000 May 3;92(9):709-20. doi: 10.1093/jnci/92.9.709.
• Background Gillison ML. Human papillomavirus and prognosis of oropharyngeal squamous cell carcinoma: implications for clinical research in head and neck cancers. J Clin Oncol. 2006 Dec 20;24(36):5623-5. doi: 10.1200/JCO.2006.07.1829. No abstract available.
• Background Ringstrom E, Peters E, Hasegawa M, Posner M, Liu M, Kelsey KT. Human papillomavirus type 16 and squamous cell carcinoma of the head and neck. Clin Cancer Res. 2002 Oct;8(10):3187-92.
• Background Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 2009 Apr 20;27(12):1992-8. doi: 10.1200/JCO.2008.20.2853. Epub 2009 Mar 16.
• Background Licitra L, Perrone F, Bossi P, Suardi S, Mariani L, Artusi R, Oggionni M, Rossini C, Cantu G, Squadrelli M, Quattrone P, Locati LD, Bergamini C, Olmi P, Pierotti MA, Pilotti S. High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol. 2006 Dec 20;24(36):5630-6. doi: 10.1200/JCO.2005.04.6136.
• Background Cmelak AJ, Li S, Goldwasser MA, Murphy B, Cannon M, Pinto H, Rosenthal DI, Gillison M, Forastiere AA. Phase II trial of chemoradiation for organ preservation in resectable stage III or IV squamous cell carcinomas of the larynx or oropharynx: results of Eastern Cooperative Oncology Group Study E2399. J Clin Oncol. 2007 Sep 1;25(25):3971-7. doi: 10.1200/JCO.2007.10.8951.
• Background Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008 Feb 20;100(4):261-9. doi: 10.1093/jnci/djn011. Epub 2008 Feb 12.
• Background Worden FP, Kumar B, Lee JS, Wolf GT, Cordell KG, Taylor JM, Urba SG, Eisbruch A, Teknos TN, Chepeha DB, Prince ME, Tsien CI, D'Silva NJ, Yang K, Kurnit DM, Mason HL, Miller TH, Wallace NE, Bradford CR, Carey TE. Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number. J Clin Oncol. 2008 Jul 1;26(19):3138-46. doi: 10.1200/JCO.2007.12.7597. Epub 2008 May 12.
• Background Rischin D, Young RJ, Fisher R, Fox SB, Le QT, Peters LJ, Solomon B, Choi J, O'Sullivan B, Kenny LM, McArthur GA. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol. 2010 Sep 20;28(27):4142-8. doi: 10.1200/JCO.2010.29.2904. Epub 2010 Aug 9.
• Background Lorch JH, Goloubeva O, Haddad RI, Cullen K, Sarlis N, Tishler R, Tan M, Fasciano J, Sammartino DE, Posner MR; TAX 324 Study Group. Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX 324 randomised phase 3 trial. Lancet Oncol. 2011 Feb;12(2):153-9. doi: 10.1016/S1470-2045(10)70279-5. Epub 2011 Jan 11.
• Background Posner MR, Lorch JH, Goloubeva O, Tan M, Schumaker LM, Sarlis NJ, Haddad RI, Cullen KJ. Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial. Ann Oncol. 2011 May;22(5):1071-1077. doi: 10.1093/annonc/mdr006. Epub 2011 Feb 11.
• Background Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS, Forastiere A, Ang KK. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol. 2008 Jul 20;26(21):3582-9. doi: 10.1200/JCO.2007.14.8841. Epub 2008 Jun 16.
• Background Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 2003 Jan 1;21(1):92-8. doi: 10.1200/JCO.2003.01.008.
• Background Forastiere A, Maor M, Weber R, Pajak, T, Glisson B, Trotti A, Ridge J, et al. Long term results of Intergroup RTOG 91-11: A Phase III trial to preserve the larynx - Induction cisplatin/5-FU and radiation therapy versus concurrent cisplatin and radiation therapy versus radiation therapy. Proceedings of the American Society of Clinical Oncology. 2006:5517.
• Background Staar S, Rudat V, Stuetzer H, Dietz A, Volling P, Schroeder M, Flentje M, Eckel HE, Mueller RP. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2001 Aug 1;50(5):1161-71. doi: 10.1016/s0360-3016(01)01544-9.
• Background Taylor SG 4th, Murthy AK, Vannetzel JM, Colin P, Dray M, Caldarelli DD, Shott S, Vokes E, Showel JL, Hutchinson JC, et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol. 1994 Feb;12(2):385-95. doi: 10.1200/JCO.1994.12.2.385.
• Background Best SR, Ha PK, Blanco RG, Saunders JR Jr, Zinreich ES, Levine MA, Pai SI, Walker M, Trachta J, Ulmer K, Murakami P, Thompson R, Califano JA, Messing BP. Factors associated with pharyngoesophageal stricture in patients treated with concurrent chemotherapy and radiation therapy for oropharyngeal squamous cell carcinoma. Head Neck. 2011 Dec;33(12):1727-34. doi: 10.1002/hed.21657. Epub 2011 Jan 18.
• Background Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan;11(1):21-8. doi: 10.1016/S1470-2045(09)70311-0. Epub 2009 Nov 10.
• Background Agoston ES, Robinson SJ, Mehra KK, Birch C, Semmel D, Mirkovic J, Haddad RI, Posner MR, Kindelberger D, Krane JF, Brodsky J, Crum CP. Polymerase chain reaction detection of HPV in squamous carcinoma of the oropharynx. Am J Clin Pathol. 2010 Jul;134(1):36-41. doi: 10.1309/AJCP1AAWXE5JJCLZ.
• Background Harris SL, Thorne LB, Seaman WT, Hayes DN, Couch ME, Kimple RJ. Association of p16(INK4a) overexpression with improved outcomes in young patients with squamous cell cancers of the oral tongue. Head Neck. 2011 Nov;33(11):1622-7. doi: 10.1002/hed.21650. Epub 2010 Dec 28.
• Background Schache AG, Liloglou T, Risk JM, Filia A, Jones TM, Sheard J, Woolgar JA, Helliwell TR, Triantafyllou A, Robinson M, Sloan P, Harvey-Woodworth C, Sisson D, Shaw RJ. Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination. Clin Cancer Res. 2011 Oct 1;17(19):6262-71. doi: 10.1158/1078-0432.CCR-11-0388.
• Background Maxwell JH, Kumar B, Feng FY, Worden FP, Lee JS, Eisbruch A, Wolf GT, Prince ME, Moyer JS, Teknos TN, Chepeha DB, McHugh JB, Urba SG, Stoerker J, Walline HM, Kurnit DM, Cordell KG, Davis SJ, Ward PD, Bradford CR, Carey TE. Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence. Clin Cancer Res. 2010 Feb 15;16(4):1226-35. doi: 10.1158/1078-0432.CCR-09-2350. Epub 2010 Feb 9.
• Background Anderson KS, Wong J, D'Souza G, Riemer AB, Lorch J, Haddad R, Pai SI, Longtine J, McClean M, LaBaer J, Kelsey KT, Posner M. Serum antibodies to the HPV16 proteome as biomarkers for head and neck cancer. Br J Cancer. 2011 Jun 7;104(12):1896-905. doi: 10.1038/bjc.2011.171.
• Background Kumar B, Cordell KG, Lee JS, Worden FP, Prince ME, Tran HH, Wolf GT, Urba SG, Chepeha DB, Teknos TN, Eisbruch A, Tsien CI, Taylor JM, D'Silva NJ, Yang K, Kurnit DM, Bauer JA, Bradford CR, Carey TE. EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. J Clin Oncol. 2008 Jul 1;26(19):3128-37. doi: 10.1200/JCO.2007.12.7662. Epub 2008 May 12.
• Background Porceddu SV, Pryor DI, Burmeister E, Burmeister BH, Poulsen MG, Foote MC, Panizza B, Coman S, McFarlane D, Coman W. Results of a prospective study of positron emission tomography-directed management of residual nodal abnormalities in node-positive head and neck cancer after definitive radiotherapy with or without systemic therapy. Head Neck. 2011 Dec;33(12):1675-82. doi: 10.1002/hed.21655. Epub 2011 Jan 14.
• Background Riemer AB, Keskin DB, Zhang G, Handley M, Anderson KS, Brusic V, Reinhold B, Reinherz EL. A conserved E7-derived cytotoxic T lymphocyte epitope expressed on human papillomavirus 16-transformed HLA-A2+ epithelial cancers. J Biol Chem. 2010 Sep 17;285(38):29608-22. doi: 10.1074/jbc.M110.126722. Epub 2010 Jul 8.
• Takahashi M, Hwang M, Misiukiewicz K, Gupta V, Miles BA, Bakst R, Genden E, Selkridge I, Botzler J, Virani V, Moshier E, Bonomi MR, Posner MR. Quality of Life Analysis of HPV-Positive Oropharyngeal Cancer Patients in a Randomized Trial of Reduced-Dose Versus Standard Chemoradiotherapy: 5-Year Follow-Up. Front Oncol. 2022 Apr 8;12:859992. doi: 10.3389/fonc.2022.859992. eCollection 2022.
• Psyrri A, Rampias T, Vermorken JB. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2014 Nov;25(11):2101-2115. doi: 10.1093/annonc/mdu265. Epub 2014 Jul 23.

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