E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced/Metastatic renal cell carcinoma with a clear cell component |
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E.1.1.1 | Medical condition in easily understood language |
Advanced/Metastatic renal cell carcinoma with a clear cell component |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038410 |
E.1.2 | Term | Renal cell carcinoma recurrent |
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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050513 |
E.1.2 | Term | Metastatic renal cell carcinoma |
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 dose response relationship in the 0.3, 2, and 10 mg/kg BMS-936558 arms as measured by Progression-free survival (PFS). |
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E.2.2 | Secondary objectives of the trial |
• To estimate PFS in the BMS-936558 arms
• To estimate the response rate in the BMS-936558 arms
• To estimate the Overall Survival (OS) in the BMS-936558 arms
• To estimate the rate of adverse events in the BMS-936558 arms
+ Exploratory Objectives:
• To evaluate changes in QTc in each treatment arm
• To estimate the immune-related response rate (irRR) and irPFS in the 2 and 10 mg/kg BMS-936558 arms relative to the 0.3 mg/kg arm
• To explore associations between PD-L1 expression in tumors and other immune response biomarkers on clinical outcome
• To characterize the pharmacokinetics of BMS-936558 and to explore exposure-safety and exposure-efficacy relationships. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologic confirmation of RCC with a clear cell component.
• Previous treatment with at least one anti-angiogenic agent
• Progressed within 6 months of study enrollment
• Subjects should not have had more than 3 prior treatments for locally advanced or metastatic disease.
• Must have available tumor tissue for submission
• Subjects must also meet various laboratory parameters for inclusion (see Protocol section 3.3.1 item 4)
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E.4 | Principal exclusion criteria |
• Active CNS metastases within 30 days of study enrollment
• Subjects with any active autoimmune disease or a history of known autoimmune disease
• Subjects with uncontrolled adrenal insufficiency
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival as measured by tumor assessments (radiographic scans) and the collection of death data. It will be compared to the doses given across the 3 treatment arms to see if a dose response exists. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumor assessments (radiographic scans) will be done every 6 weeks from randomization for the first 12 months, then every 12 weeks until progression is documented.
Subjects will be assessed for survival every 3 months. |
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E.5.2 | Secondary end point(s) |
• Progression free survival in the BMS-936558 arms
• The tumor response rate in the BMS-936558 arms as assessed by the Investigator assessment of best overall response
• The overall survival in the BMS-936558 arms as collected by death data
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Progression free survival will be assessed in each individual treatment arm by tumor assessments every 6 weeks
• The tumor response rate will be assessed on all subjects at the time they discontinue study treatment by the Investigators assessment of best overall response for a subject
• The survival in each treatment arm will be assessed by the collection of death data every 3 months following the discontinuation of study therapy until a subjects death
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
Canada |
Finland |
Italy |
United States |
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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
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Survival follow-up may continue for up to 5 years from the primary analysis of the PFS. The study will end once 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 | 3 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |