E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or metastatic urothelial or non-urothelial carcinoma of the urinary tract |
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E.1.1.1 | Medical condition in easily understood language |
Urothelial cancer is a type of cancer that affects the urinary tract. It includes cancer of the bladder, ureters, and renal pelvis. |
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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 | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 safety of atezolizumab |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of atezolizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 years
- Histologically documented locally advanced (tumor (T) 4b, any node (N); or any T, N 2−3) or metastatic (M1, Stage IV) urothelial or non-urothelial carcinoma of the urinary tract
- Patients with measurable and non-measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 are allowed
- Must have received one prior combination chemotherapy regimen (e.g., methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC], gemcitabine and cisplatin [GC], etc.) for inoperable, locally advanced or metastatic urothelial or non-urothelial carcinoma of the urinary tract
- Representative formalin-fixed paraffin-embedded (FFPE) tumor specimen block available for submission at baseline
- Eastern cooperative oncology group (ECOG) performance status 0, 1 or 2
- Life expectancy >= 12 weeks
- Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 2 weeks prior to the first study treatment
- Patients with treated, asymptomatic central nervous system (CNS) metastases are eligible (Note: Patients on stable doses of anticonvulsants or on prednisone doses [or dose equivalents] of <= 20 milligram/day are allowed)
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use 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
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E.4 | Principal exclusion criteria |
- Treatment with more than three prior lines of systemic therapy for inoperable, locally advanced or metastatic urothelial or non-urothelial carcinoma of the urinary tract
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to study treatment initiation
- Treatment with chemotherapy within 2 weeks prior to study treatment initiation
- Treatment with radiotherapy ongoing at the time of study entry (for CNS-directed radiotherapy)
- Pregnant or lactating, or intending to become pregnant during the study
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
- Significant cardiovascular disease, such as New York Heart Association cardiac disease >= Class III, myocardial infarction within 3 months, unstable arrhythmias, or unstable angina
- Significant renal disorder requiring dialysis or indication for renal transplant
- Signs or symptoms of severe infection within 2 weeks prior to initiation of study treatment, including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Major surgical procedure within 4 weeks prior to study treatment initiation or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- History of autoimmune disease are allowed if controlled and on stable treatment (i.e., same treatment, same dose) for the last 12 weeks
- Prior allogeneic stem cell or solid organ transplantation
- History of idiopathic pulmonary fibrosis (including pneumonitis, drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C
- Active tuberculosis
- Administration of a live, attenuated vaccine within 4 weeks prior to study treatment initiation
- Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, including anti− cytotoxic T lymphocyte-associated (CTLA)-4, anti− programmed cell death protein 1 (PD-1), and anti− programmed death-ligand 1 (PD-L1) therapeutic antibodies
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to initiation of study treatment
- Specifically for patients without autoimmune disease, treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to study treatment initiation or anticipated requirement for systemic immunosuppressive medications during the study treatment period. Note: For patients with autoimmune disease, immunosuppressive medications are permitted if the patient has controlled autoimmune disease and stable treatment (i.e., same treatment, same dose) for the previous 12 weeks
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Nature, severity, duration, frequency and timing of adverse events
2.Changes in vital signs, physical findings, and clinical laboratory results during and following atezolizumab administration
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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.Overall survival (OS)
2.Progression-free survival (PFS)
3.Overall response rate (ORR)
4.Disease control rate (DCR)
5.Duration of response (DoR)
6.Change from baseline in health-related quality of life (HRQoL), as assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30)
7.EuroQol EQ-5D-5L-assessed health utility score
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 140 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
China |
Colombia |
Croatia |
Czech Republic |
Denmark |
Egypt |
Estonia |
Germany |
Greece |
Hungary |
Ireland |
Italy |
Lithuania |
Netherlands |
Poland |
Portugal |
Romania |
Russian Federation |
Saudi Arabia |
Spain |
Switzerland |
United Kingdom |
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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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When all patients enrolled have either died, withdrawn consent, are lost to follow up, or have been followed for 48 months since the last study patient is enrolled, whichever occurs first |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |