E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Urothelial cancer |
Carcinoma uroteliale |
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E.1.1.1 | Medical condition in easily understood language |
Bladder cancer |
Cancro della vescica |
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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 | 10005003 |
E.1.2 | Term | Bladder cancer |
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 |
The primary objective of the study is: * To evaluate the objective response rate of the selected dose regimen out of 2 possible dose regimens (Regimen 1: 10 mg dose, 7 days on/7 days off; and regimen 2: 6 mg dose, 21 days on/7 days off) in subjects with metastatic or surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations. |
• Valutare il tasso di risposta oggettiva (risposta completa [CR]+ risposta parziale [PR]) del regime di dosaggio selezionato tra 2 possibili regimi (regime 1: dose da 10 mg, 7 giorni sì/7 giorni no; e regime 2: dose da 6 mg, 21 giorni sì/7 giorni no) in soggetti con carcinoma uroteliale metastatico o non asportabile chirurgicamente, caratterizzati da specifiche alterazioni genomiche dell’FGFR. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: * To evaluate the objective response rate in chemo-refractory subjects * To evaluate the progression-free survival (PFS), duration of response, and overall survival in all and chemo-refractory subjects *To evaluate the response rate in biomarker-specific subgroups (translocations versus mutations) * To evaluate the safety and pharmacokinetics of JNJ-42756493 at the 2 dose regimens |
• Valutare il tasso di risposta oggettiva nei soggetti refrattari a chemioterapia. • Valutare la sopravvivenza senza progressione (PFS), la durata della risposta e la sopravvivenza globale in tutti i soggetti e nei soggetti refrattari a chemioterapia. • Valutare il tasso di risposta in sottogruppi specifici per biomarcatori (traslocazioni vs. mutazioni). • Valutare la sicurezza e la farmacocinetica di JNJ-42756493 nei 2 regimi di dosaggio. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Must have histologic demonstration of metastatic or surgically unresectable urothelial cancer. Minor components of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable - Must have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline - Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1, or 2 - Must have adequate bone marrow, liver, and renal function as described in protocol - Negative pregnancy test (urine or serum beta human chorionic gonadotropin [b-hCG]) at Screening for women of child bearing potential who are sexually active |
- Presenza dimostrata istologicamente di carcinoma uroteliale metastatico o non asportabile chirurgicamente. Sono accettabili componenti minori di variante istologica come una differenziazione squamosa o ghiandolare oppure evoluzione a fenotipi più aggressivi come la variante sarcomatoide o micropapillare. - Malattia misurabile in base ai criteri di valutazione della risposta nei tumori solidi (RECIST, versione 1.1) al basale. - Punteggio del performance status ECOG pari a 0, 1 o 2 (Allegato 1 al protocollo di studio - Funzionalità midollare, epatica e renale adeguata, come descritto nel protocollo. - Test di gravidanza negativo (beta-hCG nel siero o nell'urina) allo screening per donne potenzialmente fertili e sessualmente attive.
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E.4 | Principal exclusion criteria |
- Received chemotherapy, targeted therapies, definitive radiotherapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and mitomycin C, within 6 weeks) before the first administration of study drug. Localized palliative radiation therapy (but should not include radiation to target lesions) and ongoing bisphosphonates and denosumab, are permitted - Has persistent phosphate level greater than upper limit of normal (ULN) during screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical management - Has a history of or current uncontrolled cardiovascular disease - Females who are pregnant, breast-feeding, or planning to become pregnant within 3 months after the last dose of study drug and males who plan to father a child while enrolled in this study or within 5 months after the last dose of study drug - Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, or Grade 1 neuropathy) |
1. Trattamenti precedenti di chemioterapia, terapie mirate, radioterapia definitiva, immunoterapia o trattamento con un agente antitumorale sperimentale nelle 2 settimane (in caso di nitrosuree e mitomicina C nelle 6 settimane) precedenti la prima somministrazione del farmaco sperimentale. Sono ammessi radioterapia palliativa localizzata (che non deve comprendere radiazioni alle lesioni target) e trattamento in corso con bifosfonati e denosumab.
2. Livello persistente di fosfato > ULN durante lo screening (entro 14 giorni dal trattamento e prima del Giorno 1 del Ciclo 1) e nonostante le cure medica.
3. Anamnesi o presenza di patologia cardiovascolare incontrollata 4. Donne in stato di gravidanza o in fase di allattamento o che prevedono una gravidanza entro tre mesi dall'ultima dose del farmaco sperimentale e uomini che pianificano il concepimento di un figlio durante l'arruolamento nel presente studio o entro i 5 mesi successivi all'ultima dose di farmaco dello studio. 5. Mancato recupero da tossicità reversibile causata da una precedente terapia antitumorale (tranne tossicità non clinicamente significative, come alopecia, scolorimento della pelle o neuropatia di grado 1).
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Participants with Best Overall Response |
Percentuale di partecipanti con la miglior risposta globale |
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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) |
1. Progression-free survival 2. Duration of Response 3. Overall survival 4. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) 5. Biomarker Assessment 6. Plasma Concentration of JNJ 42756493 7. Plasma Clearance of JNJ 42756493 8. Volume of Distribution of JNJ 42756493 |
1. Sopravvivenza libera da progressione 2. Durata della risposta 3. Sopravvivenza globale 4. Numero di partecipanti con eventi avversi (AEs) ed eventi avversi seri (SAEs) 5. Valutazione biomarkers 6. Concentrazione plasmatica di JNJ 42756493 7. Clearance plasmatica di JNJ 42756493 8. Volume di distribuzione di JNJ 42756493
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/2. From the date of the first dose of study drug until disease progression or death as assessed up to the last efficacy assessment for disease progression (approx 3yrs 9m) 3. From the date of the first dose of study drug until death (up to 3yrs 9m) 4. Screening up to end of study (approx 3yrs 9m) 5/6/7/8. Baseline up to end of study (approx 3 years 9 months)
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1/2. Dalla data della prima dose di trattamento in studio fino a progressione di malattia o decesso valutato fino all’ultima valutazione di efficacia per progressione di malattia (ca. 3 anni e 9 mesi) 3. Dalla data della prima dose di trattamento in studio fino al decesso (fino a 3 anni e 9 mesi) 4. Dallo screening fino alla fine dello studio (ca. 3 anni e 9 mesi) 5/6/7/8 Dalla baseline fino alla fine dello studio (ca. 3 anni e 9 mesi)
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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 |
Biomarker testing |
Test dei biomarcatori |
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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 | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
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.8.2.4 | 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 | 60 |
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 |
Korea, Republic of |
Romania |
Russian Federation |
Spain |
Taiwan |
United Kingdom |
United States |
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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
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The end of study is defined as approximately 12 months after last subject is enrolled or anytime the Sponsor terminates the study. |
La fine dello studio è approssimativamente 12 mesi dopo l'arruolamento dell'ultimo soggetto o quando lo Sponsor decide di terminare lo studio |
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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 | 2 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |