BCG treatment failure or intolerance, high-risk non-muscle invasive bladder cancer
Conditions
Interventions
5.0×10^7 PFU group:Herpes Virus T3011 Injection
5.0×10^8 PFU group:Herpes Virus T3011 Injection
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Willingness to provide written informed consent Form (ICF) and ability to comply with ICF. 2.Age >= 18 years. 3.Histopathologically confirmed urothelial carcinoma of the bladder. 4.High-risk NMIBC patients who were diagnosed by clinical cystoscopy, urine cytology and histopathology within 8 weeks before the first administration, and who failed or were intolerant to BCG treatment after TURBT, and were not suitable for or unwilling to receive radical cystectomy. 5.BCG treatment failure: including BCG refractory tumors, recurrent tumors after BCG treatment, BCG non-responsive tumors, BCG intolerance, as detailed below: (1) BCG refractory tumors: a. T1G3/HG uroepithelial carcinoma occurred within 3 months of BCG treatment; b. The development of TaG3/HG urothelial carcinoma after 3-6 months of BCG treatment, i.e. after secondary induction or maintenance therapy; c. Cancer in situ (without papillary tumor) occurs after 3 months of BCG treatment, and complete remission can be achieved in more than 50% of cases with 1 additional cycle of BCG induction therapy. If the carcinoma in situ persists after 6 months of reinduction or the first maintenance treatment, it is a BCG-refractory tumor. d. High-grade NMIBC occurred during BCG maintenance therapy. (2) Recurrent tumors after BCG treatment: Initially BCG treatment responded, but there was a recurrence of G3/HG tumors in the bladder after BCG maintenance treatment was completed. (3) BCG-unresponsive tumors: including BCG-refractory tumors; Recurrence of T1Ta/HG tumors within 9 months after completion of adequate BCG treatment; Carcinoma in situ developed within 9 months after completion of adequate BCG treatment. Adequate BCG treatment was defined as completion of at least five of the initial six induction treatments, and completion of at least two of the second cycle of induction or maintenance therapy. (4) BCG intolerance: cessation of BCG use due to severe adverse reactions prior to completion of BCG treatment. 6.All tumors showed no visible tumor after transurethral resection of bladder tumors (TURBT). If it meets the requirements of secondary electrical cutting, it is necessary to perform secondary electrical cutting. Secondary resection was recommended for patients with insufficient initial TURBT, no muscular tissue in the initial resection specimen (except for low-grade [TaGl] tumors and simple in-situ carcinoma), stage T1 tumors, and high-grade [G3] tumors (except simple in-situ carcinoma); Secondary electrocution is recommended 2 to 6 weeks after primary electrocution. Patients undergoing secondary resection should be satisfied with no visible tumor after surgery. 7.Eastern Cooperative Oncology Group (ECOG) performance status is 0 or 1. 8.Expected survival time is more than 3 months. 9.Adequate hematologic and end-organ function within 4 weeks prior to the first study treatment as follows: Adequate bone marrow reserve and organ function: • Hematology (no treatment such as transfusion or colony-stimulating factor within 14 days): ANC >= 1.5 x 10^9/L, PLT >= 75 x 10^9/L, Hb >= 90 g/L. • Liver function: TBIL = 30 ml/min (calculated according to the Cockcroft-Gault formula). • Coagulation function: activated partial thromboplastin time (APTT) <= 1.5 × ULN, prothrombin time (PT) <= 1.5 × ULN, and international normalized ratio (INR) <= 1.5 × ULN. 10.Fertile women should agree that they must take
Exclusion criteria
Exclusion criteria: 1.Diagnosed as muscular invasive bladder cancer (T2-T4). 2.Patients with upper and lower urethral urothelial carcinoma or lymph node or distant metastasis. 3.Pregnant and lactating female patients. 4.Major surgical procedure within 4 weeks prior to first use of study drug or anticipated need for major surgical procedure other than diagnostic during the course of the study. 5.With the exception of immediate postoperative TURBT perfusion therapy, treatment with antitumor drugs such as chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy, etc. (except nitrosoureas, mitomycin C, oral fluorouracil analogs, small molecule targeted drugs, and traditional Chinese medicines with antitumor indications) within 4 weeks prior to the first use of the study drug, nitrosoureas, or mitomycin C within 6 weeks prior to the first use of the study drug, oral fluorouracil analogs and small molecule targeted drugs within 2 weeks prior to the first use of the study drug or within 5 half-lives of the drug (whichever is longer), and traditional Chinese medicines with antitumor indications within 2 weeks prior to the first use of the study drug. 6.Patients who have received systemic corticosteroids (prednisone > 10 mg/day or equivalent dose of similar drug) or other immunosuppressive therapy within 14 days prior to first use of study drug, except for the following: treatment with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids, and short-term prophylactic use of corticosteroids (e.g., to prevent allergy to contrast media). 7.Administration of a live attenuated vaccine within 4 weeks prior to the first administration of study drug or anticipation of the need for such a live attenuated vaccine during the study. 8.Prior treatment with oncolytic viruses (e.g., T-vec, T3011, etc.), gene therapy, cell therapy, or tumor vaccines. 9.History of splenectomy or history of organ transplantation. 10.Patients with malignant tumors other than those treated in this study, except for the following: • Malignancies that have been treated with the goal of cure and = 5 years from the first administration of trial drug, have no known active disease, and have a low risk of potential recurrence. • Adequately treated non-melanoma skin cancer or malignant freckle-like nevus without evidence of disease. • Adequately treated carcinoma in situ without evidence of disease. 11.Complications due to prior antineoplastic therapy that have recovered to grade =1 according to CTCAE 5.0 (except alopecia areata) including, but not limited to, urinary tract infections, signs of urinary tract irritation, and hematuria of the naked eye. 12.Retained ureteral stent or had a history of vesicoureteral reflux. 13.Significant cardiovascular disease such as New York Heart Association heart disease (Class II or higher), myocardial infarction within 3 months prior to enrollment, unstable arrhythmia or unstable angina. 14.History of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndromes, Wegener's granulomatosis, desiccation syndrome, Greene-Barry syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Exceptions are patients with hypothyroidism or diabetes mellitus who are well controlled on replacement therapy. 15.Persistent or active infec
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first study dose;Complete Response or Recurrence-Free Survival at 3, 6, 9, 12, 15, 18, 21 and 24 Months After First Study Drug Use;SAE;Abnormal clinically significant vital signs, physical examination and laboratory findings, etc.;AE;PFS;DLT;RFS;One-year survival rate;Incidence of radical cystectomy; | — |
Countries
China
Contacts
Public ContactYe Dingwei
Fudan University Shanghai Cancer Center
Outcome results
None listed