Bladder cancer
Conditions
Interventions
1. Drug Atezolizumab 1200 mg/body Administered intravenously every 3 weeks for up to 1 year 2. Radiotherapy cavity of lesser pelvis (41.4 Gy/23 Fr) Next, whole bladder (16.2 Gy/9 Fr) Atezolizum
Sponsors
Nishiyama Hiroyuki
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed UC of the bladder by TURBT within 90 days prior to study registration. Patients who received 2nd-TURBT, the date of surgery within 90 days prior to study registration (Histologically confirmed by TURBT diagnosis of UC of the bladder within 150 days prior to study registration). 2. Histologically confirmed cT1-3N0M0 (UICC/AJCC 8th edition) invasive bladder cancer 1) Tumor stage cT1N0M0 Patients must satisfy one of more of the following: a. Multiple T1 carcinoma (2 and more) b. Residual T1 lesion by 2nd-TUR c. T1 carcinoma with CIS d. BCG-resistant T1 carcinoma e. BCG-intolerant recurrent T1 carcinoma 2) Tumor stage cT2-3N0M0 Maximum lesion diameter 5 cm and more 3. Life expectancy 3 years and more 4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 5. The following laboratory results obtained within 14 days prior to the first dose of Atezolizumab. a. WBC counts 2500/microliter and more b. ANC 1500 cells/microliter and more c. Lymphocyte count 300/microliter and more d. Platelet count 100,000/microliter and more e. Hemoglobin 9.0 gram/deciliter and more f. AST, ALT and alkaline phosphatase 2.5-fold or less the upper limit of normal (ULN) g. Total bilirubin 1.0-fold or less ULN h. Serum creatinine 2.5-fold or less ULN or Calculated creatinine clearance 30 milliliter/min and more (Cockcroft-Gault formula) i. PTT/PT 1.5-fold or less ULN or PT-INR 1.7-fold or less ULN 6. Women of childbearing potential must agree to remain abstinent or use contraceptive methods that result in a failure rate of less than 1% per year during the treatment period and for at least 5 months after the last dose of investigational agent. 7. Men has a partner as woman of childbearing potential must agree to use contraception as 6 above during the treatment period and for at least 33 weeks after the last dose of investigational agent.
Exclusion criteria
Exclusion criteria: 1. Patients with cT4 of bladder cancer, UTUC or urethra cancer 2. Hydronephrosis. Patients with hydronephrosis derived from TURBT are eligible for this study. 3. Breastfeeding and pregnancy 4. Malignancies within 5 years prior to enrollment other than as follow: 1) Bladder cancer and UTUC as tumor stage of below pTa/pTis 2) Localized malignancy treated with expected curative intent 5. Active or history of autoimmune disease include suspected 6. Patients have a disease that needs treatment with systemic corticosteroids or other systemic immunosuppressive medications within 14 days prior to the first dose of investigational agent 7. Prior treatment with an anti-PD1, anti-PDL1, anti-PDL2 or anti-CTLA4 therapeutic antibodies (including other therapeutic antibodies or drug specifically targeting T cell costimulation or immune checkpoint pathways) 8. Previous pelvic radiation therapy 9. Prior chemotherapy, radiation therapy, biological drug (including BCG intravesical instillation) or treatment with investigational agent. Intravesical chemotherapy (single time) is eligible for this study. 10. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 11. Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the Atezolizumab formulation 12. Serum albumin <2.5 g/dL 13. Positive test for HIV 14. Patients with active hepatitis B virus or hepatitis C 15. Active tuberculosis 16. Active or history of interstitial lung disease or pulmonary fibrosis diagnosed by imaging and clinical finding 17. Sever infections within 4 weeks prior to the first dose of investigational agent 18. Signs or symptoms of infection within 2 weeks prior to the first dose of investigational agent 19. Receipt of therapeutic oral or IV antibiotics within 2 weeks prior to the first dose of investigational agent 20. Significant cardiovascular disease 21. Intractable infection, inflammation disease in irradiation region on study registration Or patients who have an inflammation disease needs systemic treatment 22. Uncontrolled diabetes mellitus 23. Major surgical procedure other than for diagnosis within 4 weeks prior the first dose of investigational agent or anticipation of need for a major surgical procedure during the course of the study 24. Prior allogeneic stem cell or solid organ transplant 25. Administration of a live, attenuated vaccine within 4 weeks before the first dose of investigational agent or anticipation that such a live ,attenuated vaccine will be required during the study 26. Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of the drug, whichever is shorter, prior to the first dose of investigational agent 27. Patients who are judged not eligible for this study by investigators
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome Name: Progression-Free Survival Metric/method of measurement: A period from the registration to any one of the PD event occurrence that is defined by the following: 1.Patient with T2 or greater bladder cancer after the point of time at 24 weeks 2. Patient with Recurrence by histological assessment in the urinary tract not including bladder after the registration 3. Patient with new lesion by imaging assessments based on RECIST guideline ver.1.1 (not including bladder) after the registration 4.Death from any cause after the registration Timepoint: At occurrence of PD event | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Outcome Name: Histologically complete response rate on 24 weeks following the first dose of investigational agent Metric/method of measurement: pCR is met the following (1) and (2): (1) Patient without bladder cancer according to histological assessment by central pathologist (2) Patient without new lesion according to imaging assessments by investigator based on RECIST guideline ver.1.1 (not including bladder) Timepoint: At 24 weeks following the first dose of investigational agent 2.Outcome Name: Recurrence-Free-Survival Metric/method of measurement: A period from the registration to any one of the recurrence event occurrence that is defined by the following: (1) Patient with recurrence in urinary tract after the registration (2) Patient with new lesion according to imaging assessments by investigator based on RECIST guideline ver.1.1 (not including bladder) (3) Death from any cause after the registration Timepoint: At occurrence of recurrence event 3. Outcome Name: Overall-Survival Metric/method of measurement: Death from any cause after the registration Timepoint: At death 4.Outcome Name: Bladder-Preservation Rate Metric/method of measurement: Bladder preservation is met all of the following:(1) Patient without having a radical cystectomy (2) Patient without recurrence of T2 or greater in bladder (3) Patient without urinary diversion (ileal conduit, ureterocutaneous fistula) Timepoint: At 2 and 3 years following the first dose of investigational agent 5. Outcome Name: Duration of CR Metric/method of measurement: A period from the date of confirmed pCR to a recurrence event occurrence that target is the patient who was confirmed pCR aton 24 weeks following the first dose of investigational product agent Timepoint: At occurrence of recurrence event | — |
Contacts
Public ContactKoichi Hashimoto
University of Tsukuba
Outcome results
None listed