E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Muscle-invasive urothelial carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Muscle-invasive urothelial carcinoma refers to cancer that has spread into the muscle wall of bladder. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022877 |
E.1.2 | Term | Invasive bladder cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of adjuvant atezolizumab treatment in patients with muscle-invasive urothelial carcinoma (UC), as measured by disease-free survival (DFS) |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of adjuvant atezolizumab treatment, as measured by overall survival (OS), disease-specific survival (DSS) distant metastasis-free survival (DMFS) and non-urinary tract recurrence-free survival (NURFS) • To evaluate the safety and tolerability of atezolizumab in the adjuvant setting • To evaluate the incidence of anti-therapeutic antibodies (ATAs) against atezolizumab and to explore the potential relationship of the immunogenicity response with pharmacokinetics (PK), safety, and efficacy • To characterize the pharmacokinetics of atezolizumab • To assess health status as measured by the EuroQol 5-dimension, 5-level version (EQ-5D-5L) questionnaire
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >=18 years - Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma [TCC]) of the bladder or upper urinary tract (i.e., renal pelvis or ureters) - Patients with upper urinary tract urothelial carcinoma (UTUC) will be limited to no more than approximately 10% of the study population - Tumor Nodes Metastasis (TNM) classification at pathological examination of surgical resection- For patients treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-4a or ypN+ (ypT2-4 or ypN+ for patients with UTUC); For patients not treated with prior neoadjuvant chemotherapy: tumor stage of pT3-T4a or pN+ (pT3-4 or pN+ for patients with UTUC) - Surgical resection of muscle-invasive UC of the bladder, or upper urinary tract - Muscle-invasive UC with programmed death ligand 1 (PD-L1) expression per immunohistochemistry (IHC) prospectively determined on the surgical resection or lymph node dissection tumor specimens by a central laboratory - Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pelvis, abdomen, and chest no more than 6 weeks prior to randomization - Full recovery from cystectomy or nephroureterectomy within 14 weeks following surgery - Eastern Cooperative Oncology Group performance status score of <=2 - Life expectancy >=12 weeks - Adequate hematologic and end-organ function - For women who are not postmenopausal (>=12 months of non−therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined non-hormonal contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab, and agreement to refrain from donating eggs during this same period |
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E.4 | Principal exclusion criteria |
- Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment - Adjuvant chemotherapy or radiation therapy for UC following surgical resection - Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment - Malignancies other than UC within 5 years prior to Cycle 1, Day 1 - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - History of autoimmune disease - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan - Tested Positive for HIV - Patients with active hepatitis B virus and tuberculosis - Prior allogeneic stem cell or solid organ transplant - Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina - Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study - Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
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E.5 End points |
E.5.1 | Primary end point(s) |
Investigator-assessed DFS |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. OS 2. DSS 3. DMFS 4. Incidence of adverse events 5. Changes in vital signs and clinical laboratory results 6. Incidence of ATA response to atezolizumab and potential correlation with PK, pharmacodynamic, safety, and efficacy parameters 7. Maximum observed serum atezolizumab concentration (Cmax) 8. Minimum observed serum atezolizumab concentration (Cmin) 9. EQ-5D-5L 10. NURFS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-5. Up to 7 years 6. Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles starting Cycle 8 until 120 days after the last dose of atezolizumab and at treatment discontinuation visit 7. Day 1 of Cycle 1 8. Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles starting Cycle 8 until 120 days after the last dose of atezolizumab and at treatment discontinuation visit 9-10. Up to 7 years
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 90 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belarus |
Belgium |
Canada |
Czech Republic |
Finland |
France |
Germany |
Greece |
Israel |
Italy |
Korea, Republic of |
Netherlands |
Poland |
Russian Federation |
Serbia |
Spain |
Switzerland |
Taiwan |
Turkey |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study as planned will occur when the required number of events for the final analysis of OS has occurred
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |