E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Venous thromboembolism (VTE) |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
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 | 10066899 |
E.1.2 | Term | Venous thromboembolism |
E.1.2 | System Organ Class | 100000004866 |
|
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 |
The primary efficacy objective is to demonstrate that rivaroxaban is
superior to placebo for reducing the risk of the primary composite
outcome as defined by objectively confirmed symptomatic lower
extremity proximal DVT, asymptomatic lower extremity proximal DVT,
symptomatic lower extremity distal DVT, symptomatic upper extremity
DVT, symptomatic non-fatal PE, incidental PE, and VTE-related death in
ambulatory adult subjects with various cancer types receiving systemic
cancer therapy who are at high risk of developing a VTE. |
|
E.2.2 | Secondary objectives of the trial |
The key secondary efficacy objectives of this study are to compare the
efficacy of rivaroxaban with placebo for reducing the risk of symptomatic
VTE events and VTE-related deaths and all-cause mortality in ambulatory
adult subjects with various cancer types receiving systemic cancer
therapy who are at high risk of developing a VTE. Other secondary
efficacy objectives include the evaluation of the individual components
of the primary efficacy composite variable analyzed separately, a
composite of confirmed fatal/non-fatal arterial thromboembolism (ATE)
events, a composite of confirmed fatal/non-fatal visceral VTE events,
and a composite of symptomatic lower extremity proximal DVT,
symptomatic lower extremity distal DVT, asymptomatic lower extremity
proximal DVT, symptomatic upper extremity DVT, non-fatal PE,
incidental PE and all-cause mortality. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically confirmed solid malignancy including but not limited to: pancreas, lung, stomach, colon, rectum, bladder, breast, ovary, renal or lymphoma (hematologic), with locally advanced or metastatic disease
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 02
- Have a Khorana thromboembolic risk Score greater than or equal
to (>=) 2
- Creatinine clearance (CrCl) >= 30 milliliter per minute (mL/min)
-Plan to initiate systemic cancer therapy within ±1 week of receiving the first dose of study drug with the intention of receiving systemic cancer therapy during the double-blind treatment period with for an intended duration determined by the treating oncologist according to standard protocols of clinical care. |
|
E.4 | Principal exclusion criteria |
- Diagnosis of primary brain tumors
- Known history of brain metastases
- Bleeding diathesis, hemorrhagic lesions, active bleeding, and other conditions with a high risk for bleeding
- Hematologic malignancies with the exception of lymphoma
- Platelet count less than (<) 50,000/millimeter^3 (mm^3), Life expectancy of less than or equal to (<=) 6 months |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1) Primary Efficacy Composite Endpoint is Time From Randomization to
First Occurrence of Objectively Confirmed Symptomatic and
Asymptomatic Lower Extremity Proximal DVT, Symptomatic Lower
Extremity Distal DVT, Symptomatic Upper Extremity DVT, Symptomatic
Non-Fatal PE, Incidental PE, or VTE-Related Death
2) The Primary Safety Objective of This Study is to Assess the Major
Bleeding Events as Defined by ISTH |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) From Randomization to Day 180 (+3 Days) as Adjudicated by an Independent CEC
2) From the Time of Randomization to Two Days After the Last Dose of Study Drug |
|
E.5.2 | Secondary end point(s) |
1) Efficacy endpoint: Symptomatic VTE Events and VTE Related Deaths
2) Efficacy endpoint: All-cause Mortality
3) Safety Endpoints Include the Proportion of Clinically Relevant Non-Major Bleeding, Minor Bleeding, any Bleeding (Defined as Major, Clinically Relevant Non-Major, and Minor Bleeding)
4) Safety endpoint: All-cause Mortality
5) Number of Participants with Adverse Events (AEs) and Serious AEs |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) and 2): Up to Day 180+3
3) From the Time of Randomization to Two Days After the Last Dose of Study Drug
4) Up to Day 180
5) Screening up to follow-up (30 days after last dose administration) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
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 | 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 | Yes |
E.8.2.3 | Other | No |
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
| 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
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 |
Belgium |
Brazil |
Bulgaria |
Canada |
Czech Republic |
France |
Germany |
Italy |
Russian Federation |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |