E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic renal cell carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038400 |
E.1.2 | Term | Renal carcinoma stage IV |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038399 |
E.1.2 | Term | Renal carcinoma stage III |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050076 |
E.1.2 | Term | Metastatic renal carcinoma |
E.1.2 | System Organ Class | 100000004864 |
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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 |
To compare subject treatment preference of tivozanib versus sunitinib |
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E.2.2 | Secondary objectives of the trial |
To compare overall safety and tolerability in subjects treated with
tivozanib and sunitinib.
To assess the frequency of dose modifications in subjects treated with
tivozanib and sunitinib.
To evaluate the Quality of Life (QoL) (including kidney-specific
symptoms and fatigue) in subjects treated with tivozanib and sunitinib. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects with unresectable mRCC
2. Histologically or cytologically confirmed RCC of any histology
3. Subjects with or without prior nephrectomy
Version 1.1 (see Appendix A).
4. ECOG performance status of 0 or 1 (see Appendix B)
5. Ability to give written informed consent and comply with protocol requirements, including drug treatments and follow-up procedures
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E.4 | Principal exclusion criteria |
1.Any prior systemic therapy (including interleukin-2, interferon-alpha, chemotherapy, bevacizumab, nvestigational or licensed drug that targets vascular endothelial growth factor [VEGF] or VEGF receptors/pathway or are mammalian target of rapamycin [mTOR] inhibitors) for treatment of mRCC
2.Significant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or coagulation disorders
3. Significant serum chemistry or urinalysis abnormalities.
4. Significant cardiovascular disease, including:
•Symptomatic Left Ventricular Dysfunction or baseline left ventricular ejection fraction (LVEF) of <= lower limit of institutional normal (LLN) ; uncontrolled hypertension; myocardial infarction; severe angina. or unstable angina within 6 months prior to administration of first dose of study drug.
•History of Class III or IV congestive heart failure
•History of serious ventricular arrhythmia
•Cardiac arrhythmias
•Coronary or peripheral artery bypass graft within 6 months of screening.
5.Corrected QT interval (QTc) of > 480 msec using Bazett’s formula.
6. Currently active second primary malignancy
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects who prefer tivozanib hydrochloride or sunitinib |
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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) |
safety and tolerability during the course of the study |
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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 | Yes |
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 |
1.subject preference of tivozanib versus sunitinib
2-QoL |
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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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
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
| 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
France |
Germany |
Italy |
Spain |
United Kingdom |
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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"Last Visit, Last Subject" |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |