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| Name | Class |
|---|---|
| Shanghai Shen Kang Hospital Development Center | OTHER |
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This study will evaluate the safety and efficacy of bladder intravesical Camrelizumab in patients with high-risk non-muscle-invasive bladder cancer who failed BCG therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intravesical therapy group | Experimental | Camrelizumab(SHR-1210) is administered on the first day of each treatment cycle (D1) at a dose up to 200 mg. The recommended phase II dose(RP2D) to be decided after safety run-in. The cycle is divided into an induction course and a maintenance course. The induction course is initiated 2 weeks after TURBT and repeat once a week for 6 weeks . After that, the maintenance course starts every 3 weeks. The maximum duration of dosing is 2 years. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Camrelizumab | Drug | Solution for Infusion (Intravesical) |
|
| Measure | Description | Time Frame |
|---|---|---|
| The maximum dose of Camrelizumab for intravesical treatment | The maximum tolerated dose (MTD) of Camrelizumab that will be given intravesically to patients with BCG-refractory NMIBC(de-escalated doses of 200/150/100mg) and recommended for phase II studies (RP2D). | 3 months after trial initiation(Phase I) |
| Event-Free Survival (EFS) | Recurrence of high-grade cancer (TaHG, T1HG, CIS), or disease progression to stage T2 or beyond or lymph node metastasis or distant metastasis, or the need for other treatment (including systemic chemotherapy, radical cystectomy, radiation therapy), and death from any cause. | 3 months after patient treatment (Phase II) |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events | Incidence of adverse events and treatment-related adverse events | Until progressive disease or death |
| Assessment of HGRF | High grade cancer recurrence free rate (HGFR) at 6 months and 1 year of treatment. |
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Inclusion Criteria:
Age ≥ 18 years.
Histologically-confirmed diagnosis of high risk non-muscle-invasive urothelial cell carcinoma of the bladder (mixed histology tumors allowed if urothelial carcinoma histology is >50%).
Fully resected disease at study entry (residual CIS acceptable).
BCG-unresponsive high risk non-muscle-invasive bladder cancer after treatment with adequate BCG therapy(at least five times a week during the induction phase and at least two times a week during the maintenance phase).
Ineligible for radical cystectomy or refusal of radical cystectomy.
Consent to tissue specimen retrieval and testing.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Adequate normal organ and marrow function as defined below:
Women of childbearing potential who have a negative serum pregnancy test within 72 hours prior to the first dose should consent to and must use effective contraception during and for 6 months after the end of the study.
Men should consent to patients who must use contraception during the study and for 6 months after the end of the study period.
The subject is personally willing and able to provide written informed consent to be able to comply with the protocol.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Xiang Wang, MD | Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine | Study Director |
| Yushan Liu, MD | Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine | Study Director |
| Xudong Yao, MD | Shanghai Tenth People's Hospital,Shanghai Tong Ji University School of Medicine | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine | Shanghai | Shanghai Municipality | 200011 | China | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15126782 | Result | Sylvester RJ, Oosterlinck W, van der Meijden AP. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomized clinical trials. J Urol. 2004 Jun;171(6 Pt 1):2186-90, quiz 2435. doi: 10.1097/01.ju.0000125486.92260.b2. | |
| 9933432 |
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| ID | Term |
|---|---|
| D001749 | Urinary Bladder Neoplasms |
| ID | Term |
|---|---|
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000631724 | camrelizumab |
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| 6 months and 1 year after patient enrollment |
| Assessment of RFS | Recurrence free survival (RFS) at 6 months and 1 year of treatment. | 6 months and 1 year after patient enrollment |
| Assessment of PFS | Progression free survival (PFS) at 6 months and 1 year of treatment. | 6 months and 1 year after patient enrollment |
| the predictive value of PD-1 expresssion | the predictive value of PD-L1 expression assessed in tumor tissue and urine sample obtained before and after Camrelizumab instillation. | 1 year after patient enrollment |
| Fudan University Shanghai Cancer Center |
| Shanghai |
| Shanghai Municipality |
| 200032 |
| China |
| Shanghai Tenth People's Hospital,Shanghai Tong Ji University School of Medicine | Shanghai | Shanghai Municipality | 200072 | China |
| Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine | Shanghai | Shanghai Municipality | 200080 | China |
| Taniguchi K, Koga S, Nishikido M, Yamashita S, Sakuragi T, Kanetake H, Saito Y. Systemic immune response after intravesical instillation of bacille Calmette-Guerin (BCG) for superficial bladder cancer. Clin Exp Immunol. 1999 Jan;115(1):131-5. doi: 10.1046/j.1365-2249.1999.00756.x. |
| 15875784 | Result | Mitropoulos DN. Novel insights into the mechanism of action of intravesical immunomodulators. In Vivo. 2005 May-Jun;19(3):611-21. |
| 25800393 | Result | Kamat AM, Flaig TW, Grossman HB, Konety B, Lamm D, O'Donnell MA, Uchio E, Efstathiou JA, Taylor JA 3rd. Expert consensus document: Consensus statement on best practice management regarding the use of intravesical immunotherapy with BCG for bladder cancer. Nat Rev Urol. 2015 Apr;12(4):225-35. doi: 10.1038/nrurol.2015.58. Epub 2015 Mar 24. |
| 23452187 | Result | Witjes JA, Palou J, Soloway M, Lamm D, Kamat AM, Brausi M, Persad R, Buckley R, Colombel M, Bohle A. Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette-Guerin (BCG): results of an international individual patient data survey (IPDS). BJU Int. 2013 Oct;112(6):742-50. doi: 10.1111/bju.12012. Epub 2013 Mar 1. |
| 24948466 | Result | Oddens JR, Sylvester RJ, Brausi MA, Kirkels WJ, van de Beek C, van Andel G, de Reijke TM, Prescott S, Witjes JA, Oosterlinck W. The effect of age on the efficacy of maintenance bacillus Calmette-Guerin relative to maintenance epirubicin in patients with stage Ta T1 urothelial bladder cancer: results from EORTC genito-urinary group study 30911. Eur Urol. 2014 Oct;66(4):694-701. doi: 10.1016/j.eururo.2014.05.033. Epub 2014 Jun 16. |
| 28796558 | Result | Chang SS, Bochner BH, Chou R, Dreicer R, Kamat AM, Lerner SP, Lotan Y, Meeks JJ, Michalski JM, Morgan TM, Quale DZ, Rosenberg JE, Zietman AL, Holzbeierlein JM. Treatment of Nonmetastatic Muscle-Invasive Bladder Cancer: American Urological Association/American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Urologic Oncology Clinical Practice Guideline Summary. J Oncol Pract. 2017 Sep;13(9):621-625. doi: 10.1200/JOP.2017.024919. Epub 2017 Aug 10. No abstract available. |
| 27324428 | Result | Babjuk M, Bohle A, Burger M, Capoun O, Cohen D, Comperat EM, Hernandez V, Kaasinen E, Palou J, Roupret M, van Rhijn BWG, Shariat SF, Soukup V, Sylvester RJ, Zigeuner R. EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol. 2017 Mar;71(3):447-461. doi: 10.1016/j.eururo.2016.05.041. Epub 2016 Jun 17. |
| 22575238 | Result | Dinney CP, Greenberg RE, Steinberg GD. Intravesical valrubicin in patients with bladder carcinoma in situ and contraindication to or failure after bacillus Calmette-Guerin. Urol Oncol. 2013 Nov;31(8):1635-42. doi: 10.1016/j.urolonc.2012.04.010. Epub 2012 May 9. |
| 24357284 | Result | Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science. 2013 Dec 20;342(6165):1432-3. doi: 10.1126/science.342.6165.1432. No abstract available. |
| 29614760 | Result | Inamura K. Bladder Cancer: New Insights into Its Molecular Pathology. Cancers (Basel). 2018 Apr 1;10(4):100. doi: 10.3390/cancers10040100. |
| 3806806 | Result | Catalona WJ, Hudson MA, Gillen DP, Andriole GL, Ratliff TL. Risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer. J Urol. 1987 Feb;137(2):220-4. doi: 10.1016/s0022-5347(17)43959-0. |
| 28583311 | Result | Pietzak EJ, Bagrodia A, Cha EK, Drill EN, Iyer G, Isharwal S, Ostrovnaya I, Baez P, Li Q, Berger MF, Zehir A, Schultz N, Rosenberg JE, Bajorin DF, Dalbagni G, Al-Ahmadie H, Solit DB, Bochner BH. Next-generation Sequencing of Nonmuscle Invasive Bladder Cancer Reveals Potential Biomarkers and Rational Therapeutic Targets. Eur Urol. 2017 Dec;72(6):952-959. doi: 10.1016/j.eururo.2017.05.032. Epub 2017 Jun 3. |
| 25838375 | Result | Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015 Apr 3;348(6230):69-74. doi: 10.1126/science.aaa4971. |
| 29368638 | Result | Zhu J, Armstrong AJ, Friedlander TW, Kim W, Pal SK, George DJ, Zhang T. Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond. J Immunother Cancer. 2018 Jan 25;6(1):4. doi: 10.1186/s40425-018-0314-1. |
| 17340590 | Result | Inman BA, Sebo TJ, Frigola X, Dong H, Bergstralh EJ, Frank I, Fradet Y, Lacombe L, Kwon ED. PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer. 2007 Apr 15;109(8):1499-505. doi: 10.1002/cncr.22588. |
| 30293387 | Result | He YT, Li DJ, Liang D, Zheng RS, Zhang SW, Zeng HM, Chen WQ, He J. [Incidence and mortality of bladder cancer in China, 2014]. Zhonghua Zhong Liu Za Zhi. 2018 Sep 23;40(9):647-652. doi: 10.3760/cma.j.issn.0253-3766.2018.09.002. Chinese. |
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |