Non-muscle invasive bladder cancer MedDRA version: 21.0 Level: PT Classification code 10005008 Term: Bladder cancer stage I, with cancer in situ System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: durvalumab
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Conce
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -BCG-naïve (patients who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before study entry are eligible). -Local histological confirmation (based on pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. A high risk tumor is defined as one of the following: - T1 tumor - High grade/G3 tumor - CIS - Multiple and recurrent and large (with diameter of largest evaluable node =3 cm) tumors (all conditions must be met in this point) -Complete resection (or as complete as possible) of all Ta/T1 papillary disease prior to randomization, with the most recent TURBT occurring 2 months or less prior to signing informed consent for this study. Patients with residual CIS after TURBT are eligible. -No prior radiotherapy to the bladder. -No prior exposure to immune-mediated therapy of cancer including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 antibodies. Patients who have been treated with anticancer vaccines will be excluded. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 292 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 683
Exclusion criteria
Exclusion criteria: -Evidence of muscle-invasive, locally advanced, metastatic, and/or extra vesical bladder cancer (ie, T2, T3, T4, and / or stage IV). -Concurrent extravesical (ie, urethra, ureter, or renal pelvis), nonmuscle-invasive transitional cell carcinoma of the urothelium. -Previous investigational product (IP) assignment in the present study. -Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer related conditions (eg, hormone replacement therapy) is acceptable. Chemotherapy for previous instances of NMIBC is acceptable. Patients who have received a single instillation of Mitomycin C or equivalent chemotherapy agent immediately after TURBT can be enrolled in the study. -Active infection including TB, hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result), hepatitis C virus (HCV), or human immunodeficiency virus (HIV [positive HIV] 1/2) antibodies. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). Appropriate TB Tests (e.g. skin or interferon gamma tests) should be performed to exclude TB infection requiring treatment. Additional clinical evaluations including clinical history, physical examination, radiographic findings, and other diagnostic procedures and specialist consultations should be performed if necessary. -Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: - Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection) - Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent - Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication) -Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener Syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: - Patients with vitiligo or alopecia - Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement - Any chronic skin condition that does not require systemic therapy - Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician - Patients with celiac disease controlled by diet alone - History of another primary malignancy except for - Malignancy treated with curative intent and with no known active disease = 2 years before the first dose of IP and of low potential risk for recurrence during study period - Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease - Adequately treated CIS without evidence of disease - Prostate cancer (tumor/node/metastasis stage) of stage = T2cN0M0 without biochemical recurrence or progression that in the opinion of the Investigator does not require active intervention
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of durvalumab + BCG combination therapy compared to BCG alone in terms of Disease Free Survival (DFS).;Secondary Objective: To assess the efficacy of the combination therapy (Durvalumab plus BCG) compared to SoC in terms of disease free at 24 months (DFS24), overall survival at 5 years (OS5), any disease-free survival (aDFS), time to muscle-invasive bladder cancer or metastatic disease, time to cystectomy and time to development of upper track urothelial carcinoma To assess the efficacy of the combination therapy (Durvalumab plus BCG) compared to SoC for patients with CIS prior to study entry or at baseline in terms of Complete response rate (CRR) at 6 month. To assess disease-related symptoms and HRQoL in patients treated with durvalumab plus BCG combination therapy compared to SoC using EORTC QLQ-C30 and EORTC QLQ NMIBC24 Tolerability using patient-reported PRO CTCAE symptoms To assess PK of durvalumab and Immunogenicity of durvalumab;Primary end point(s): Disease-free survival (DFS);Timepoint(s) of evaluation of this end point: Patients will be assessed by investigator tumor assessments every 3 months relative to the date of randomization until month 36, and then every 6 months according to standard of care or until disease progression. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Disease free at 24 months (DFS24) Survival at 5 years (OS5) Complete response rate (CRR) Any disease-free survival (aDFS) Time to muscle-invasive bladder (MIBC) cancer or metastasis Time to cystectomy Time to development of upper track urothelial carcinoma (UTUC) Disease related Symptoms Patient reported treatment tolerability Assessment of PK of Durvalumab Immunogenicity of Durvalumab (ADA) in combination with BCG;Timepoint(s) of evaluation of this end point: DFS24, OS5, aDFS, Time to MIBC, metastasis, cystectomy and UTUC will be assessed by disease assessments every 3 months until month 36 and then every 6 months. CRR will be assessed at 6 month Disease related symptoms will be assessed with EORTC QLQ-C30 and EORTC QLQ NMIBC24 questionnaires at the 1st week of treatment and every 4 and 8 weeks until the end of the disease assessment period Patient reported treatment tolerability will be assessed by PRO-CTCAE questionnaires every 4 weeks until the end of the disease assessment period. Concentration of Durvalumab (PK) will be assessed 5 times: pre- dose and post- dose for week 1, pre-dose at week 5 and week 25 and at week 12 of the follow-up period. ADA and nAB will be assessed 4 times: week 1, week 5, week 25 and week 12 of follow-up period | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Japan, Netherlands, Poland, Russian Federation, Slovakia, Spain, United Kingdom
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed