E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic or unresectable urothelial cancer |
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E.1.1.1 | Medical condition in easily understood language |
metastatic or unresectable urothelial cancer |
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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 | 10046723 |
E.1.2 | Term | Urothelial carcinoma ureter |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10046714 |
E.1.2 | Term | Urothelial carcinoma bladder |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 | 10064467 |
E.1.2 | Term | Urothelial carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 | 10005003 |
E.1.2 | Term | Bladder cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 | 10046728 |
E.1.2 | Term | Urothelial carcinoma urethra |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of the study is to measure the effect of nivolumab (BMS-936558) in reducing tumor size in subjects with metastatic or unresectable bladder cancer. |
|
E.2.2 | Secondary objectives of the trial |
-To evaluate progression free survival (using RECIST 1.1) in subjects based on assessments by an independent review committee
-To evaluate overall survival in subjects as assessed by the investigator
-To estimate overall response rate (using RECIST 1.1) in subjects as assessed by the investigator |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a. Evidence of metastatic or surgically unresectable transitional cell carcinoma of the urothelium involving the bladder, urethra, ureter, or renal pelvis.
b. Measurable disease by CT or MRI
c. Progression or recurrence after treatment
i) with at least 1 platinum-containing chemotherapy regimen for metastatic or surgically-unresectable locally advanced urothelial cancer, or
ii) within 12 months of peri-operative (neo-adjuvant or adjuvant) treatment with platinum agent in the setting of cystectomy for localized muscle-invasive urothelial cancer.
d)Subjects that have received more than 2 prior lines of chemotherapy must not have liver metastases.
e) tumor tissue (archived or new biopsy) must be provided for biomarker analysis
f) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. |
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E.4 | Principal exclusion criteria |
a.Subjects with active cancer that has spread to the central nervous system.
b.Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
c.Subjects with active, known or suspected autoimmune disease.
d.Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
e.Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, anti-CD137, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
Exclusion laboratory criteria:
- Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The overall response rate (using RECIST 1.1) to nivolumab (BMS-936558) based on a independent review committee in subjects with metastatic or unresectable bladder cancer |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Eight weeks after the subject's first dose and then every 8 weeks after up to 48 weeks, then every 12 weeks until disease progression or study drug is discontinued |
|
E.5.2 | Secondary end point(s) |
-To evaluate progression free survival (using RECIST 1.1) in subjects based on assessments by an independent review committee
-To evaluate overall survival in subjects as assessed by the investigator
-To estimate overall response rate (using RECIST 1.1) in subjects as assessed by the investigator |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
-For progression free survival: Eight weeks after the subject's first dose and then every 8 weeks after up to 48 weeks, then every 12 weeks until disease progression or study drug discontinued.
-For overall survival: Every 3 months during the survival follow-up phase up to a maximum of 5 years
-for overall response rate: Eight weeks after the subject's first dose and then every 8 weeks after up to 48 weeks, then every 12 weeks until disease progression or study drug discontinued |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker Assessments, Outcomes Research Assessments,
Immunogenicity Assessments |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Belgium |
Czech Republic |
Finland |
Germany |
Italy |
Japan |
Poland |
Spain |
Sweden |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
The study will end when survival follow-up has concluded. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 11 |
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 | 1 |