Assessing the safety of atezolizumab being directly administered to the bladder in bladder cancer patients undergoing radical cystectomy
- Conditions
- rothelial cell carcinoma of the bladderCancer
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 56
1. Patient must be fully informed about the study and have signed the informed consent form
2. Patients with mixed histologies are required to have predominant urothelial cell carcinoma in the bladder
3. Patients with pTis to T4N0 M0 for whom radical cystectomy is planned treatment for their urothelial cell carcinoma of the bladder. Radical cystectomy must be scheduled at least 6 weeks after confirmation of eligibility. This will include both MIBC and high-grade NMIBC tumours.
4. Patients with MIBC must be ineligible for cisplatin-based neo-adjuvant chemotherapy or have declined neoadjuvant chemotherapy
5. Aged 18 years old and over
6. Performance status: Eastern Co-operative Oncology Group (ECOG) 0-2
7. Patient must be willing and able to comply with the protocol, have mental capacity and (if a woman of childbearing potential [WOCBP]) use effective contraception throughout treatment and for 5 months after treatment completion
8. Have diagnostic biopsy tissue material (i.e., transurethral resection of bladder tumour [TURBT] sample) available for use in the trial
9. Adequate organ function within 28 days prior to confirmation of eligibility and 7 days of study treatment as defined below:
9.1. White blood cell count (WBC): >2X10^9/L
9.2. Lymphocyte count: = 0.5 x 10^9/L (= 500/µL)
9.3. Neutrophils: =1.5 X10^9/L
9.4. Platelets: =100 X10^9/L
9.5. Estimated glomerular filtration rate (eGFR): >30mL/min
9.6.Serum total bilirubin: <1.5 x upper limit of normal (ULN) OR =3 ULN in a patient with Gilbert’s Syndrome AND direct bilirubin =ULN
9.7.Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT): =1.5 x ULN
9.8.Haemoglobin: =90g/L
9.9.Urine dipstick: Negative for nitrites. (If positive then a negative MSU is required. If positive MSU then infection must be treated prior to starting treatment.)
1. Active urinary tract infection in last 2 weeks prior to assessing eligibility.
2. Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteraemia, or severe pneumonia, or any active infection that could impact patient safety.
3. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease (COPD) exacerbation) are eligible for the study.
4. Presence of indwelling urinary stent or history of vesico-ureteric reflux.
5. Other intravesical therapy within 2 weeks of assessing eligibility.
6. Prior radiotherapy to bladder or planned radiotherapy to bladder.
7. Reduced bladder capacity (defined as an inability to hold an intravesical instillation for 1 hour).
8. Positive pregnancy test (as eligibility assessment for WOCBP), breast-feeding women, patients intending to become pregnant during and within 5 months after last dose of atezolizumab, or patients unwilling to comply with contraception requirements.
9. Patients with active, known, or suspected autoimmune disease with the following exceptions:
9.1. Patients with vitiligo or alopecia;
9.2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement;
9.3. Any chronic skin condition that does not require systemic therapy;
9.4. Patients with coeliac disease controlled by diet alone;
9.5. Patients with Crohn’s disease or ulcerative colitis (must be inactive stable disease).
10. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor-a [TNF-a] agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
10.1. Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
10.2. Patients who received mineralocorticoids (e.g., fludrocortisone), inhaled or low dose corticosteroids for COPD or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
11. Positive test for hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV).
12. Patients considered a poor medical risk by the investigator due to a serious, uncontrolled medical disorder, non-malignant system disease or active uncontrolled infection. Examples include but are not limited to; active COVID-19 infection, any psychiatric disorder that prohibits obtaining informed consent or protocol compliance.
13. Prior systemic immune checkpoint inhibitor therapy (prior BCG is permitted).
14. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method