Immunotherapy Clinical Trial
Official title:
A Phase I/II Single Arm Study of Intravesical Administration With Camrelizumab for High-risk Non-muscle Invasive Bladder Cancer(NMIBC) Failing in BCG Treatment
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.
Status | Recruiting |
Enrollment | 25 |
Est. completion date | December 2024 |
Est. primary completion date | February 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Age = 18 years. 2. 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%). 3. Fully resected disease at study entry (residual CIS acceptable). 4. 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). 5. Ineligible for radical cystectomy or refusal of radical cystectomy. 6. Consent to tissue specimen retrieval and testing. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8. Adequate normal organ and marrow function as defined below: 1. Haemoglobin (HB) = 90 g/L 2. Absolute neutrophil count (ANC) =1.5×10^9/L(no granulocyte colony-stimulating factor support for 2 weeks before day 1 of cycle 1) 3. Lymphocyte count=0.500×10^9/L 4. Platelet count =100×10^9/L(No blood transfusions within 2 weeks before day 1 of cycle 1) 5. 4.0×10^9/L=White Blood Cell Count (WBC)=15×10^9/L 6. AST (SGOT)/ALT (SGPT)/Alkaline phosphatase = 2.5 x institutional upper limit of normal(ULN) (excluded Gilbert's disease patients, whose serum bilirubin level = 3x ULN) 7. INR/aPTT=1.5×ULN(Which only applies to patients not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be given a stable dose) 8. Serum creatinine (Cr) = 1.5 times the upper institutional limit of normal (ULN) or Serum creatinine Cl>60 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) 9. 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. 10. Men should consent to patients who must use contraception during the study and for 6 months after the end of the study period. 11. The subject is personally willing and able to provide written informed consent to be able to comply with the protocol. Exclusion Criteria: 1. Muscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma. 2. Concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis)urothelial cell carcinoma. 3. Have participated in a clinical trial of an investigational drug or device within 4 weeks prior to receiving the first treatment in this project. 4. Received chemotherapy, targeted small molecule therapy, immunotherapy or radiation therapy following a recent cystoscopy or transurethral resection of a bladder tumour. 5. History of other malignancies within the last 5 years. 6. Active autoimmune disease that has required systemic treatment in the past 2 years. 7. History of idiopathic pulmonary fibrosis (including pneumonia), drug-induced pneumonia, histoplasmosis (i.e. occlusive bronchiolitis, cryptogenic histoplasmosis), or evidence of active pneumonia on chest CT scan (history of fibrosis in radiation pneumonia), patients with active tuberculosis. 8. Active infection requiring systemic therapy,therapeutic oral or intravenous (IV) antibiotics within 14 days prior to enrolment (patients receiving prophylactic antibiotics (e.g. for the prevention of urinary tract infections or chronic obstructive pulmonary disease) can be enrolled). 9. Patients who are pregnant or breastfeeding, or expecting to conceive . 10. Previous treatment with anti-PD-1 monoclonal antibody, PD-L1 monoclonal antibody, CTLA-4 monoclonal antibody, or other drugs that act on T-cell co-stimulation or any other antibody of the checkpoint pathway. 11. Patients with known positive test for human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS). 12. Patients with known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (Hepatitis B reference: HBsAg positive and HBV DNA = 500 IU/ml; Hepatitis C reference: HCV antibody positive and HCV viral copy number > upper limit of normal value). 13. Received a live virus vaccine within 30 days of planned start of study treatment. 14. Has had an allogeneic tissue/solid organ transplant. 15. Long-term oral steroids, more than 10 mg/day of methandrostenolone or similar, must be stopped for 28 days before entry into the group. 16. Evidence of apparently uncontrolled concomitant disease that may affect compliance with the protocol or interpretation of the results, including significant liver disease (e.g. cirrhosis, uncontrolled major seizures or superior vena cava syndrome). 17. Significant cardiovascular disease, such as New York Heart Association heart attack (class II or higher), myocardial infarction, unstable arrhythmia or unstable angina within 3 months prior to study entry. 18. Patients who have had major surgery within 4 weeks prior to study entry, or who are expected to require major surgery during the course of the study, except diagnostic procedures such as TURBT or biopsy. 19. History of autoimmune diseases, including but not limited to severe muscle weakness, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, angio-thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, dry syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. 20. History of severe allergy, sensitisation or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins. 21. Patients who, in the opinion of the investigator, are otherwise unable to participate in this trial. |
Country | Name | City | State |
---|---|---|---|
China | Fudan University Shanghai Cancer Center | Shanghai | Shanghai |
China | Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine | Shanghai | Shanghai |
China | Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine | Shanghai | Shanghai |
China | Shanghai Tenth People's Hospital,Shanghai Tong Ji University School of Medicine | Shanghai | Shanghai |
Lead Sponsor | Collaborator |
---|---|
Fudan University | Shanghai Shen Kang Hospital Development Center |
China,
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 — View Citation
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. — View Citation
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/Amer — View Citation
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. — View Citation
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 — View Citation
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. — View Citation
Inamura K. Bladder Cancer: New Insights into Its Molecular Pathology. Cancers (Basel). 2018 Apr 1;10(4):100. doi: 10.3390/cancers10040100. — View Citation
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 — View Citation
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. — View Citation
Mitropoulos DN. Novel insights into the mechanism of action of intravesical immunomodulators. In Vivo. 2005 May-Jun;19(3):611-21. — View Citation
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 s — View Citation
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 Can — View Citation
Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015 Apr 3;348(6230):69-74. doi: 10.1126/science.aaa4971. — View Citation
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 — View Citation
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 — View Citation
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 baci — View Citation
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 — View Citation
* Note: There are 17 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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) | |
Primary | 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) | |
Secondary | Incidence of adverse events | Incidence of adverse events and treatment-related adverse events | Until progressive disease or death | |
Secondary | Assessment of HGRF | High grade cancer recurrence free rate (HGFR) at 6 months and 1 year of treatment. | 6 months and 1 year after patient enrollment | |
Secondary | Assessment of RFS | Recurrence free survival (RFS) at 6 months and 1 year of treatment. | 6 months and 1 year after patient enrollment | |
Secondary | Assessment of PFS | Progression free survival (PFS) at 6 months and 1 year of treatment. | 6 months and 1 year after patient enrollment | |
Secondary | 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 |
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