| Eligibility |
Inclusion Criteria:
1. Age = 18 years on the day of signing informed consent form.
2. Patients who have NMIBC which is confirmed by cystoscopy, urine cytology and
histopathology examination within 12 weeks prior to the first dose, and is classified
as high risk according to the Guideline of Non-muscle Invasive Bladder Cancer issued
by European Association of Urology (EAU) (version 2021)
3. CIS patients must have CIS on the tumor sample from the most recent cystoscopy/TURBT.
4. Patients who have papillary tumors (Ta and T1), a complete TURBT must have been
performed, as characterized by:
-Attainment of a visually complete resection of all papillary tumors (Ta and T1);
-Residual CIS, therefore not amenable to complete transurethral resection is
acceptable;
- The most recent cystoscopy/TURBT must have been performed within 12 weeks prior
to the first dose.
5. Patients who have received and failed BCG intravesical instillation therapy prior to
enrollment and are ineligible for radical cystectomy or elect not to undergo the
procedure.
Failure of BCG therapy including: BCG refractory tumor, BCG relapsing tumor, BCG
unresponsive tumor
6. Patients who have elected not to undergo the radical cystectomy or are ineligible for
the procedure on the investigator's judgment. The reasons for ineligible or refusal of
radical cystectomy should be discussed with the patient as part of the informed
consent and should be documented on the appropriate case report form. Ineligibility
factors for radical cystectomy include, but are not limited to:
-Patients have cardiovascular disease (e.g., recent acute coronary syndrome, cardiac
arrhythmias, heart failure);
-Patients have chronic obstructive pulmonary disease that would preclude a safe
surgical procedure, as determined by the treating surgeon;
-Patients have undergone major abdominal and pelvic surgery that would preclude a safe
surgical procedure, as determined by the treating surgeon.
7. Patients who have a performance status of 0 or 1 on the ECOG performance scale
8. Adequate organ function during the screening period, include:
-Absolute neutrophil count (ANC) = 1.5 × 10^9/L;
-Hemoglobin (Hgb) = 80 g/L;
-Platelets (PLT) = 100 × 10^9/L;
-ALT and AST = 2.5 × ULN, or = 5.0 × ULN for subject with liver metastases;
- Total bilirubin (TBIL) = 1.5×ULN;
- Serum creatinine (Cr) = 1.5 × ULN, or creatinine clearance = 30 mL/min according
to the Cockcroft Gault formula
- All premenopausal women and women within 12 months of menopause with a negative
serum pregnancy test;
- Left ventricular ejection fraction (LVEF) = 50%;
- Prothrombin time (PT) or international normalized ratio (INR) = 1.5 x ULN, unless
the subject is receiving anticoagulant therapy. Patients should be waited for at
least 1 week to do the above tests if they have received thrombopoietin and/or
granulocyte colony-stimulating factor.
9. Expected survival time of more than 6 months
10. Eligible patients of childbearing potential (men and women) must agree to use a
reliable method of contraception (including intrauterine device, contraceptive or
condom for females; condom or abstinence for males) with their partners prior to the
study entry, during the trial, and for at least 180 days after completion of
treatment. In addition, female patients should be non-lactating.
11. Patients must be informed of the study prior to the trial and voluntarily sign a
written informed consent form.
Exclusion Criteria:
1. Patients who are known allergy or intolerance to investigational product, BCG or
excipients.
2. Patients who have muscle-invasive bladder cancer (T2-T4) confirmed.
3. Patients who have concurrent extra-vesical (i.e., urethral, ureter or renal pelvis)
non-muscle invasive transitional cell carcinoma of the urothelium.
4. Patients who have a history of vesicoureteral reflux.
5. Patients who have not recovered from toxicity reactions associated with prior
antitumor therapy except for fatigue and alopecia (determination criteria: toxicity
remains > Grade 1 or has not returned to baseline levels).
6. Patients who have severe or uncontrollable cardiac diseases which need to be treated,
including:
1). patients with severe arrhythmias (ventricular arrhythmias which requires clinical
intervention, second to third degree of atrioventricular block, etc.); 2). patients with a
medical history of myocardial infarction, unstable angina, angioplasty, or coronary artery
bridging surgery within 6 months prior to the first dose of the investigational product;
3). patients with Class III or IV of congestive heart failure classified by NYHA 4).
corrected QTc interval is > 450 ms for men and > 470 ms for women (calculated by the
Fridericia formula) by 12-lead ECG at screening.
7. Patients who have received intravesical instillation therapy within 28 days prior to the
first dose (patients are allowed to have immediate chemotherapeutic instillation in the
past and after the current electrodesiccation); 8. Patients who have received antitumor
therapy such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, biologic
therapy and herbal medicine within 28 days or 5 half-lives of the drug (whichever is
longer) prior to the first dose.
9. Patients who have participated in any other clinical trial (except for patients at
overall survival follow-up) within 28 days or 5 half-lives of the drug (whichever is
longer) prior to the first dose.
10. Patients who have additional malignancy that have had progression or requires active
treatment in the last 3 years. Exceptions include, but are not limited to, in situ cervical
cancer, superficial or non-invasive bladder cancer, basal cell carcinoma, in situ squamous
cell carcinoma, or gastrointestinal tumors confined to the mucosal layer and that have been
endoscopically resected.
11. Patients who have received allogeneic stem cell or solid organ transplantation.
12. Patients who have received any live/attenuated vaccine within 4 weeks or blood
transfusion within 2 weeks prior to enrollment. 13. Patients who have received extensive
radiotherapy to the pelvis (> 30% of the bone marrow area).
14. Patients who have an active autoimmune disease that have required systemic therapy in
the past 2 years (i.e., with use of corticosteroids or immunosuppressive drugs).
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement
therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
therapy.
15. Patients who have a diagnosis of immunodeficiency or are receiving systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days prior to the planned
first dose. The use of physiologic doses of corticosteroids may be approved after
consultation with the sponsor.
16. Patients who have serious or poorly controlled disease, including but not limited to:
1. . active tuberculosis (with clinical signs, physical examination findings or
radiographic findings of active tuberculosis);
2. . hepatitis B virus (HBV) infection with HBV DNA positive (>upper limit of detection
values in the site), hepatitis C virus (HCV) infection with HCV RNA positive (>upper
limit of detection values in the site), and human immunodeficiency virus (HIV) test
positive;
3. . uncontrolled hypertension after treatment (defined as systolic blood pressure =160
mmHg and/or diastolic blood pressure =100 mmHg);
4. . severe and uncontrollable pulmonary disease (severe infectious pneumonia,
interstitial lung disease, etc.) (=Grade 3, CTCAE);
5. . uncontrolled all types of serious infections (=Grade 3, CTCAE), including active or
refractory urinary tract infections.
6. . ascites, pleural effusion or pericardial effusion requiring drainage prior to first
study drug therapy.
17. Patients with known history of psychiatric disorder, substance abuse, drug and alcohol
use that would interfere with the subject's ability to cooperate with the requirements of
the trial.
18. Patients who are inappropriate for participation in this trial in the opinion of the
investigator.
|
