Clinical trial NCT04570410: Primary Excision Combined With Preoperative Neoadjuvant and Adjuvant Therapy for Oligometastasis of Urothelial Carcinoma
Official title: Trials of Primary Excision Combined With Preoperative Neoadjuvant Therapy and Adjuvant Therapy Was Used as a First-line Comprehensive Therapy for Oligometastasis of Urothelial Carcinoma（UC）.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Urothelial Carcinoma
Keywords: Oligometastasis
PD-1
Gemcitabine plus cisplatin
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2020-09-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: treatment of primary focal resection plus lymph node dissection combined with chemotherapy and anti-programmed cell death 1(PD-1) for Oligometastasis of urothelial carcinoma.

Detailed description: The study is designed to demonstrate that Whether the perioperative comprehensive treatment of primary focal resection plus lymph node dissection combined with chemotherapy and anti-PD-1 can prolong the overall survival of patients, narrow the range of metastatic lesions and improve the quality of life of patients.

Compared with patients with extensive metastasis, 2-year tumor-specific survival and overall survival of patients with oligometastatic bladder cancer were significantly increased (53.3% vs 16.1%)；(51.9% vs. 15.4%).Gemcitabine plus cisplatin (GC) regimen has been shown to bring clinical benefits in neoadjuvant therapy of metastatic UC（urothelial carcinoma）.

PD-1 inhibitors have been widely used in urothelial carcinoma in recent years, and positive data have been obtained in both advanced patients and neoadjuvant patients.

If successful in this trial, it will serve to provide a therapeutic alternative for this patient who have oligometastasis of urothelial carcinoma.

Eligibility criteria: Inclusion Criteria:

* Patients with oligometastatic urothelial carcinoma, including :patients with T2-T4 with any metastasis(T4NxM1) urothelial carcinoma diagnosed by pathology and evaluated by imaging;
* Patients with measurable oligometastasis or with local lymph node metastasis. Measurable oligometastasis includes: A. a solitary metastatic organ, B. number of metastatic lesions of ≤3, C. the largest diameter of metastatic foci of ≤5cm, D. absence of liver metastasis. Local lymph node metastasis includes: A. for tumors of the bladder and lower ureter, the short diameter of pelvic lymph nodes was ≥8 mm B. for tumors of the renal pelvis and upper ureter, the short diameter of renal hilar lymph nodes was ≥8 mm. The researchers assessed the benefits of excision of the primary lesion.
* Older than 18 years old.
* Volunteer to participate in the trial, be able to provide a written informed consent, and understand and agree to comply with the study requirements and evaluation schedule.
* Eastern Cooperative Oncology Group (ECOG) performance status \<2
* International standardized ratio or activated partial thrombin time ≤1.5 upper limit of normal value (ULN);The calculated creatinine clearance rate was ≥60ml/min;Serum total bilirubin ≤1.5×ULN;aspartate transaminase(AST), Alanine transaminase(ALT) and alkaline phosphatase ≤2.5×ULN;
* Non-pregnant or fertile men or women must be willing to take effective contraceptive measures during the study period and ≥120 days after the last administration of tislelizumab, and the women should be negative on urine or serum pregnancy test results less than or equal to 7 days before enrollment.

Exclusion Criteria:

* Previous therapy targeted at PD-1, PD-L1, PD-L2, Cytotoxic T-Lymphocyte Associated Protein 4(CTLA-4)or other antibodies or drugs specifically targeting T cell synergistic stimulation or checkpoint channels.
* Other approved systemic anti-cancer therapies or systemic immune modulators (including but not limited to interferon, interleukin-2, and tumor necrosis factor) were received within 28 days prior to enrollment.
* Severe chronic or active infections requiring systemic antimicrobial, antifungal, or antiviral therapy within 14 days prior to enrollment.
* Major surgery or major trauma occurred within 28 days prior to enrollment.
* Live vaccine was administered within 28 days before enrollment.
* Received any herbal or proprietary Chinese medicine used to control cancer in the 14 days prior to enrollment.
* Active autoimmune disease requiring long-term use of large amounts of hormones and other immunosuppressive agents.
* The researchers identified abnormalities in potassium, sodium, calcium, or hypoalbuminemia, interstitial lung disease, non-infectious pneumonia, or other uncontrolled whole-body diseases, including diabetes, hypertension, and cardiovascular disease, that may affect treatment.
* A history of HIV, hepatitis B virus(HBV)and hepatitis C virus(HCV) infection is known.
* A history of known allergic reactions to any of the drugs studied.
* Is participating in additional clinical studies.
* The researcher believes that the patient is not suitable to participate in this study (such as the treatment that does not meet the patient's greatest benefit, patient compliance, etc.)

Primary outcomes:
measure: 1 year overall survival(OS) rate
timeFrame: 1 year
Secondary outcomes:
measure: progression-free survival(PFS)
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The first affiliated hospital of Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Qiang Lv
role: PRINCIPAL_INVESTIGATOR
References:
citation: Erratum: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2020 Jul;70(4):313. doi: 10.3322/caac.21609. Epub 2020 Apr 6. No abstract available.
citation: Rosenberg JE, Carroll PR, Small EJ. Update on chemotherapy for advanced bladder cancer. J Urol. 2005 Jul;174(1):14-20. doi: 10.1097/01.ju.0000162039.38023.5f.
citation: Bajorin DF, Dodd PM, Mazumdar M, Fazzari M, McCaffrey JA, Scher HI, Herr H, Higgins G, Boyle MG. Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol. 1999 Oct;17(10):3173-81. doi: 10.1200/JCO.1999.17.10.3173.
citation: Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995 Jan;13(1):8-10. doi: 10.1200/JCO.1995.13.1.8. No abstract available.
citation: Seisen T, Sun M, Leow JJ, Preston MA, Cole AP, Gelpi-Hammerschmidt F, Hanna N, Meyer CP, Kibel AS, Lipsitz SR, Nguyen PL, Bellmunt J, Choueiri TK, Trinh QD. Efficacy of High-Intensity Local Treatment for Metastatic Urothelial Carcinoma of the Bladder: A Propensity Score-Weighted Analysis From the National Cancer Data Base. J Clin Oncol. 2016 Oct 10;34(29):3529-3536. doi: 10.1200/JCO.2016.66.7352.
citation: Dong F, Shen Y, Gao F, Xu T, Wang X, Zhang X, Zhong S, Zhang M, Chen S, Shen Z. Prognostic value of site-specific metastases and therapeutic roles of surgery for patients with metastatic bladder cancer: a population-based study. Cancer Manag Res. 2017 Nov 14;9:611-626. doi: 10.2147/CMAR.S148856. eCollection 2017.
citation: Horwich A, Babjuk M, Bellmunt J, Bruins HM, De Reijke TM, De Santis M, Gillessen S, James N, Maclennan S, Palou J, Powles T, Ribal MJ, Shariat SF, Van Der Kwast T, Xylinas E, Agarwal N, Arends T, Bamias A, Birtle A, Black PC, Bochner BH, Bolla M, Boormans JL, Bossi A, Briganti A, Brummelhuis I, Burger M, Castellano D, Cathomas R, Chiti A, Choudhury A, Comperat E, Crabb S, Culine S, De Bari B, DeBlok W, De Visschere PJL, Decaestecker K, Dimitropoulos K, Dominguez-Escrig JL, Fanti S, Fonteyne V, Frydenberg M, Futterer JJ, Gakis G, Geavlete B, Gontero P, Grubmuller B, Hafeez S, Hansel DE, Hartmann A, Hayne D, Henry AM, Hernandez V, Herr H, Herrmann K, Hoskin P, Huguet J, Jereczek-Fossa BA, Jones R, Kamat AM, Khoo V, Kiltie AE, Krege S, Ladoire S, Lara PC, Leliveld A, Linares-Espinos E, Logager V, Lorch A, Loriot Y, Meijer R, Carmen Mir M, Moschini M, Mostafid H, Muller AC, Muller CR, N'Dow J, Necchi A, Neuzillet Y, Oddens JR, Oldenburg J, Osanto S, Oyen WJG, Pacheco-Figueiredo L, Pappot H, Patel MI, Pieters BR, Plass K, Remzi M, Retz M, Richenberg J, Rink M, Roghmann F, Rosenberg JE, Roupret M, Rouviere O, Salembier C, Salminen A, Sargos P, Sengupta S, Sherif A, Smeenk RJ, Smits A, Stenzl A, Thalmann GN, Tombal B, Turkbey B, Vahr Lauridsen S, Valdagni R, Van Der Heijden AG, Van Poppel H, Vartolomei MD, Veskimae E, Vilaseca A, Vives Rivera FA, Wiegel T, Wiklund P, Williams A, Zigeuner R, Witjes JA. EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committeesdagger. Ann Oncol. 2019 Nov 1;30(11):1697-1727. doi: 10.1093/annonc/mdz296.
citation: Ogihara K, Kikuchi E, Watanabe K, Kufukihara R, Yanai Y, Takamatsu K, Matsumoto K, Hara S, Oyama M, Monma T, Masuda T, Hasegawa S, Oya M. Can urologists introduce the concept of "oligometastasis" for metastatic bladder cancer after total cystectomy? Oncotarget. 2017 Dec 4;8(67):111819-111835. doi: 10.18632/oncotarget.22911. eCollection 2017 Dec 19.