Intravesical GEM/DOCE for HR BCG-Unresponsive NMIBC

Summary

The goal of this clinical trial is to learn whether a combination of two chemotherapy drugs, Gemcitabine and Docetaxel, can treat high-grade non-muscle-invasive bladder cancer (HG-NMIBC) in adults whose cancer failed conventional BCG therapy. The drugs are given directly into the bladder (intravesically), one immediately after the other. The study will also assess the safety of this treatment. The main questions it aims to answer are: Can this drug combination effectively treat HG-NMIBC that did not respond to BCG and help prevent the cancer from coming back, offering long-term protection? What side effects or medical issues do participants experience during treatment? Researchers will evaluate this non-surgical approach as a potential alternative to bladder removal surgery (radical cystectomy), with the goal of validating it as a bladder-sparing option in this setting. Participants will: * Go through a screening process, including tumor removal and imaging tests * Receive weekly bladder treatments with Gemcitabine followed by Docetaxel for 6 weeks * If the cancer responds, continue with similar once monthly treatments (maintenance therapy) for up to 2 years * Attend regular check-ups, including bladder exams, urine tests, biopsies, and optional quality-of-life surveys * Possibly receive a second 6-week treatment cycle if the cancer returns early * Be followed for up to 5 years to monitor long-term outcomes

Timeline

Start

2026-04-10

Primary completion

2033-01-01

Completion

2033-01-01

Publications

• Background Ben-David R, Tillu N, Alerasool P, Bieber C, Ranti D, Tolani S, Eisenhauer J, Chung R, Lavallee E, Waingankar N, Attalla K, Wiklund P, Mehrazin R, Anderson CB, Sfakianos JP. Induction and maintenance of sequential intravesical gemcitabine/docetaxel for intermediate and high-risk non-muscle invasive bladder cancer with different dosage protocols. World J Urol. 2024 May 11;42(1):315. doi: 10.1007/s00345-024-04992-5.
• Background Daniels MJ, Barry E, Milbar N, Schoenberg M, Bivalacqua TJ, Sankin A, Kates M. An evaluation of monthly maintenance therapy among patients receiving intravesical combination gemcitabine/docetaxel for nonmuscle-invasive bladder cancer. Urol Oncol. 2020 Feb;38(2):40.e17-40.e24. doi: 10.1016/j.urolonc.2019.07.022. Epub 2019 Aug 28.
• Background McElree IM, Mott SL, O'Donnell MA, Packiam VT. Alternative instillation techniques of sequential intravesical gemcitabine and docetaxel for non-muscle-invasive bladder cancer. BJU Int. 2024 Jun;133(6):671-673. doi: 10.1111/bju.16208. Epub 2023 Oct 26. No abstract available.
• Background Alghafees M, Chakra MA, Alkhayal A, Moussa M, Alkhamees M, Alsaikhan B, Alasker A, Alsayyari A, Alsaghyir A, Alkahtani A, O'Donnell MA. Saudi urologists' treatment pattern for high-risk Bacillus Calmette-Guerin naive and Bacillus Calmette-Guerin unresponsive nonmuscle invasive bladder cancer. Urol Ann. 2025 Jan-Mar;17(1):58-63. doi: 10.4103/ua.ua_43_24. Epub 2025 Jan 18.
• Background Abou Chakra M, Shore ND, Dillon R, O'Donnell MA. US Clinical Practice Patterns of Intravesical Chemotherapy for Bacillus Calmette-Guerin-Unresponsive and Bacillus Calmette-Guerin-Exposed Nonmuscle-Invasive Bladder Cancer. Urol Pract. 2024 Jan;11(1):97-107. doi: 10.1097/UPJ.0000000000000481. Epub 2023 Oct 30.
• Background Abou Chakra M, Packiam VT, Duquesne I, Peyromaure M, McElree IM, O'Donnell MA. Combination intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) as first-line or rescue therapy: where do we stand now? Expert Opin Pharmacother. 2024 Feb;25(2):203-214. doi: 10.1080/14656566.2024.2310073. Epub 2024 Jan 30.
• Background McElree IM, Steinberg RL, Mott SL, O'Donnell MA, Packiam VT. Comparison of Sequential Intravesical Gemcitabine and Docetaxel vs Bacillus Calmette-Guerin for the Treatment of Patients With High-Risk Non-Muscle-Invasive Bladder Cancer. JAMA Netw Open. 2023 Feb 1;6(2):e230849. doi: 10.1001/jamanetworkopen.2023.0849.
• Background Yim K, Melnick K, Mott SL, Carvalho FLF, Zafar A, Clinton TN, Mossanen M, Steele GS, Hirsch M, Rizzo N, Wu CL, Mouw KW, Wszolek M, Salari K, Feldman A, Kibel AS, O'Donnell MA, Preston MA. Sequential intravesical gemcitabine/docetaxel provides a durable remission in recurrent high-risk NMIBC following BCG therapy. Urol Oncol. 2023 Nov;41(11):458.e1-458.e7. doi: 10.1016/j.urolonc.2023.06.018. Epub 2023 Sep 9.
• Background Chevuru PT, McElree IM, Mott SL, Steinberg RL, O'Donnell MA, Packiam VT. Long-term follow-up of sequential intravesical gemcitabine and docetaxel salvage therapy for non-muscle invasive bladder cancer. Urol Oncol. 2023 Mar;41(3):148.e1-148.e7. doi: 10.1016/j.urolonc.2022.10.030. Epub 2022 Nov 28.
• Background Steinberg RL, Thomas LJ, Brooks N, Mott SL, Vitale A, Crump T, Rao MY, Daniels MJ, Wang J, Nagaraju S, DeWolf WC, Lamm DL, Kates M, Hyndman ME, Kamat AM, Bivalacqua TJ, Nepple KG, O'Donnell MA. Multi-Institution Evaluation of Sequential Gemcitabine and Docetaxel as Rescue Therapy for Nonmuscle Invasive Bladder Cancer. J Urol. 2020 May;203(5):902-909. doi: 10.1097/JU.0000000000000688. Epub 2019 Dec 10.
• Background Balar AV, Kamat AM, Kulkarni GS, Uchio EM, Boormans JL, Roumiguie M, Krieger LEM, Singer EA, Bajorin DF, Grivas P, Seo HK, Nishiyama H, Konety BR, Li H, Nam K, Kapadia E, Frenkl T, de Wit R. Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol. 2021 Jul;22(7):919-930. doi: 10.1016/S1470-2045(21)00147-9. Epub 2021 May 26.
• Background Brahmer JR, Long GV, Hamid O, Garon EB, Herbst RS, Andre T, Armand P, Bajorin D, Bellmunt J, Burtness B, Choueiri TK, Cohen EEW, Diaz LA Jr, Shitara K, Kulkarni G, McDermott D, Shah M, Tabernero J, Vogel A, Zinzani PL, Jafari N, Bird S, Snyder E, Gause C, Bracco OL, Pietanza MC, Gruber T, Ribas A. Safety profile of pembrolizumab monotherapy based on an aggregate safety evaluation of 8937 patients. Eur J Cancer. 2024 Mar;199:113530. doi: 10.1016/j.ejca.2024.113530. Epub 2024 Jan 11.
• Background Cookson MS, Chang SS, Lihou C, Li T, Harper SQ, Lang Z, Tutrone RF. Use of intravesical valrubicin in clinical practice for treatment of nonmuscle-invasive bladder cancer, including carcinoma in situ of the bladder. Ther Adv Urol. 2014 Oct;6(5):181-91. doi: 10.1177/1756287214541798.
• Background Narayan VM, Boorjian SA, Alemozaffar M, Konety BR, Shore ND, Gomella LG, Kamat AM, Bivalacqua TJ, Montgomery JS, Lerner SP, Busby JE, Poch M, Crispen PL, Steinberg GD, Schuckman AK, Downs TM, Mashni J Jr, Lane BR, Guzzo TJ, Bratslavsky G, Karsh LI, Woods ME, Brown G, Canter D, Luchey A, Lotan Y, Inman BA, Williams MB, Cookson MS, Chang SS, Sankin AI, O'Donnell MA, Sawutz D, Philipson R, Parker NR, Yla-Herttuala S, Rehm D, Jakobsen JS, Juul K, Dinney CPN. Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guerin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial. J Urol. 2024 Jul;212(1):74-86. doi: 10.1097/JU.0000000000004020. Epub 2024 May 5.
• Background Necchi A, Roumiguie M, Kamat AM, Shore ND, Boormans JL, Esen AA, Lebret T, Kandori S, Bajorin DF, Krieger LEM, Niglio SA, Uchio EM, Seo HK, de Wit R, Singer EA, Grivas P, Nishiyama H, Li H, Baranwal P, Van den Sigtenhorst-Fijlstra M, Kapadia E, Kulkarni GS. Pembrolizumab monotherapy for high-risk non-muscle-invasive bladder cancer without carcinoma in situ and unresponsive to BCG (KEYNOTE-057): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2024 Jun;25(6):720-730. doi: 10.1016/S1470-2045(24)00178-5. Epub 2024 May 10.
• Background Steinberg G, Bahnson R, Brosman S, Middleton R, Wajsman Z, Wehle M. Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group. J Urol. 2000 Mar;163(3):761-7.
• Background Al Hussein Al Awamlh B, Chang SS. Novel Therapies for High-Risk Non-Muscle Invasive Bladder Cancer. Curr Oncol Rep. 2023 Feb;25(2):83-91. doi: 10.1007/s11912-022-01350-9. Epub 2022 Dec 26.
• Background Shabsigh A, Korets R, Vora KC, Brooks CM, Cronin AM, Savage C, Raj G, Bochner BH, Dalbagni G, Herr HW, Donat SM. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol. 2009 Jan;55(1):164-74. doi: 10.1016/j.eururo.2008.07.031. Epub 2008 Jul 18.
• Background Novara G, Catto JW, Wilson T, Annerstedt M, Chan K, Murphy DG, Motttrie A, Peabody JO, Skinner EC, Wiklund PN, Guru KA, Yuh B. Systematic review and cumulative analysis of perioperative outcomes and complications after robot-assisted radical cystectomy. Eur Urol. 2015 Mar;67(3):376-401. doi: 10.1016/j.eururo.2014.12.007. Epub 2015 Jan 2.
• Background Chang SS, Boorjian SA, Chou R, Clark PE, Daneshmand S, Konety BR, Pruthi R, Quale DZ, Ritch CR, Seigne JD, Skinner EC, Smith ND, McKiernan JM. Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline. J Urol. 2016 Oct;196(4):1021-9. doi: 10.1016/j.juro.2016.06.049. Epub 2016 Jun 16.
• Background Holzbeierlein JM, Bixler BR, Buckley DI, Chang SS, Holmes R, James AC, Kirkby E, McKiernan JM, Schuckman AK. Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment. J Urol. 2024 Apr;211(4):533-538. doi: 10.1097/JU.0000000000003846. Epub 2024 Jan 24.
• Background Broughton EI, Chun DS, Gooden KM, Mycock KL, Rajkovic I, Taylor-Stokes G. Treatment and disease management patterns for bacillus Calmette-Guerin unresponsive nonmuscle invasive bladder cancer in North America, Europe and Asia: A real-world data analysis. Curr Urol. 2022 Sep;16(3):147-153. doi: 10.1097/CU9.0000000000000072. Epub 2022 Aug 2.
• Background Broughton EI, Gooden KM, Mycock KL, Rajkovic I, Taylor-Stokes G. Multi-country clinical practice patterns, including use of biomarkers, among physicians' treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). BMC Urol. 2022 Feb 26;22(1):27. doi: 10.1186/s12894-022-00959-z.
• Background Collacott H, Krucien N, Heidenreich S, Catto JWF, Ghatnekar O. Patient Preferences for Treatment of Bacillus Calmette-Guerin-unresponsive Non-muscle-invasive Bladder Cancer: A Cross-country Choice Experiment. Eur Urol Open Sci. 2023 Jan 31;49:92-99. doi: 10.1016/j.euros.2022.12.016. eCollection 2023 Mar.
• Background Moussa M, Abou Chakra M, Shore ND, Papatsoris A, Farahat Y, O'Donnell MA. Patterns of treatment of high-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) patients among Arab urologists. Arch Ital Urol Androl. 2024 Mar 19;96(1):12244. doi: 10.4081/aiua.2024.12244.
• Background Joudi FN, Smith BJ, O'Donnell MA, Konety BR. Contemporary management of superficial bladder cancer in the United States: a pattern of care analysis. Urology. 2003 Dec;62(6):1083-8. doi: 10.1016/s0090-4295(03)00765-9.

Drugs

Indications