E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Renal Cell Carcinoma |
Cancer du rein métastatique |
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E.1.1.1 | Medical condition in easily understood language |
Advanced kidney cancer |
Cancer du rein métastatique |
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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 | 18.1 |
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 compare the progression-free survival (PFS) of subjects with refractory advanced renal cell carcinoma (RCC) randomized to treatment with tivozanib hydrochloride (tivozanib) or sorafenib as assessed by blinded independent radiological review (IRR) of computerized tomography (CT) or magnetic resonance imaging
(MRI). |
Comparer la survie sans progression (SSP) chez les patients atteints de carcinome des cellules rénales (CCR) réfractaire à un stade avancé ayant été randomisés pour recevoir un traitement par chlorhydrate de tivozanib (tivozanib) ou par sorafénib, d'après des clichés de tomodensitométrie (TDM) ou d'imagerie par résonance magnétique (IRM) revus de manière indépendante et en insu. |
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E.2.2 | Secondary objectives of the trial |
To compare the overall survival (OS) of subjects randomized to treatment with tivozanib or sorafenib.
To compare objective response rate (ORR) and duration of response (DoR) of subjects randomized to treatment with tivozanib or sorafenib.
To compare the safety and tolerability of tivozanib and sorafenib. |
Comparer la survie globale (SG) chez les patients ayant été randomisés pour recevoir un traitement par tivozanib ou sorafénib
Comparer le taux de réponse objective (TRO) et la durée de la réponse (DdR) chez les patients ayant été randomisés pour recevoir un traitement par tivozanib ou sorafénib
Comparer la sécurité d’emploi et la tolérance associés au tivozanib ou au sorafénib.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. ≥ 18-years of age.
2. Subjects with recurrent metastatic RCC who have failed 2 or 3 prior systemic regimens, one of which includes a VEGFR TKI other than sorafenib or tivozanib.
3. Subjects must have recovered from the AEs of prior therapy or returned to baseline, and be off all therapy for at least 2 weeks.
4. Histologically or cytologically confirmed RCC with a clear cell component (subjects with pure papillary cell tumor or other non-clear cell histologies, including collecting duct, medullary, chromophobe, mixed tumor containing predominantly sarcomatoid cells, and unclassified RCC are excluded).
5. Measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Life expectancy ≥ 3 months.
8. If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment.
9. Ability to give written informed consent and comply with protocol. |
1. ≥ à 18 ans.
2. Patient atteint d’un CCR récurrent métastatique n’ayant pas répondu à deux ou trois traitements systémiques précédents, dont l’un doit avoir comporté un ITK du VEGFR autre que le sorafénib ou le tivozanib.
3. Le patient doit s’être rétabli des effets indésirables du traitement précédent ou être revenu à la situation initiale, et ne doit avoir reçu aucun traitement depuis au moins 2 semaines.
4. CCR confirmé par un examen histologique ou cytologique, avec une composante à cellules claires (les patients présentant un carcinome papillaire pur ou une autre histologie à cellules non claires, dont tube collecteur, médullaire, chromophobe, tumeur mixte contenant principalement des cellules sarcomatoïdes et CCR non classé ne peuvent être inclus).
5. Maladie mesurable selon les critères d’évaluation de la réponse vis-à-vis des tumeurs (Response Evaluation Criteria in Solid Tumors [RECIST]) version 1.1.
6. Indice de performance de l’ECOG (Eastern Cooperative Oncology Group) de 0 ou 1.
7. Espérance de vie ≥ 3 mois.
8. Test de grossesse négatif documenté avant l’inclusion dans l’étude pour les femmes en âge de procréer.
9. Patient apte à donner son consentement éclairé par écrit et à se conformer aux exigences du protocole.
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E.4 | Principal exclusion criteria |
1. Prior treatment with sorafenib or tivozanib.
2. More than 3 prior regimens for metastatic RCC.
3. Known central nervous system (CNS) diseases other than stable, treated brain metastases, defined as primary CNS malignancies or CNS metastases
4. Significant cardiovascular disease
5. Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug
6. Significant bleeding disorders
7. Currently active second primary malignancy
8. Pregnant or lactating females.
9. Participation in another interventional protocol. |
1. Traitement précédent par sorafénib ou tivozanib.
2. Plus de 3 protocoles de traitement précédents pour CCR métastatique.
3. Maladies connues du système nerveux central (SNC) autres que des métastases cérébrales stables et traitées, définies comme des affections malignes primitives du SNC ou des métastases au niveau du SNC
4. Affection cardiovasculaire significative
5. Accident thromboembolique ou troubles vasculaires significatifs au cours des 6 mois précédant l’administration de la première dose de médicament à l’étude
6. Troubles hémorragiques significatifs
7. Deuxième affection maligne primitive actuellement active
8. Femme enceinte ou qui allaite.
9. Participation à une autre étude interventionnelle.
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E.5 End points |
E.5.1 | Primary end point(s) |
• To compare the PFS of subjects dosed with tivozanib with those subjects dosed with sorafenib. |
•Comparer la survie sans progression (SSP) chez les patients traités par tivozanib avec ceux traités par sorafénib. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Analysis will be done at the time of the final PFS analysis. |
L'analyse sera effectuée au moment de l'analyse finale de la survie sans progression (SSP) |
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E.5.2 | Secondary end point(s) |
• To compare the OS between the 2 treatment arms by using stratified Log-rank test and the stratification factors included in the primary analysis.
• To analyze OS, ORR, and DoR using the investigator and independent radiological review assessments.
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•Comparer la survie globale (SG) entre les deux groupes de traitement en utilisant le test du log-rank stratifié et les facteurs de stratification inclus dans l'analyse principale
•Analyser la survie globale (SG), le taux de réponse objective (TRO) et la durée de la réponse (DdR) en utilisant les évaluations de l'investigateur et de la revue radiologique indépendante. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The interim OS analysis will be done at the time of the final PFS analysis.
The final OS analysis will be performed when all subjects have been lost to follow-up, have withdrawn consent, or have died, or when all subjects in follow-up have been on-study for at least 2 years, whichever occurs first. |
L'analyse intermédiaire de la survie globale (SG) sera effectuée au moment de l'analyse finale de la survie sans progression (SSP)
L'analyse finale de la survie globale (SG) sera effectuée lorsque tous les patients seront perdus de vue ou auront retiré leur consentement ou seront décédés ou quand tous les patients auront été suivi pendant au moins 2 ans, selon celui qui se produira en premier |
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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 | Yes |
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 |
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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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 77 |
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 |
Canada |
Czech Republic |
Denmark |
France |
Germany |
Hungary |
Israel |
Italy |
New Zealand |
Poland |
Spain |
Sweden |
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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End of the trial - when all subjects have been lost to follow-up, have withdrawn consent, or have died, or when all subjects in follow-up have been on-study for at least 2 years, whichever occurs first. |
Fin de l'étude - lorsque tous les patients seront perdus de vue ou auront retiré leur consentement ou seront décédés ou quand tous les patients auront été suivi pendant au moins 2 ans, selon celui qui se produira en premier |
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |