E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Urothelial cancer |
Cáncer urotelial |
|
E.1.1.1 | Medical condition in easily understood language |
Bladder cancer |
Cáncer de vejiga |
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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. |
El objetivo primario del estudio es: * Evaluar la tasa de respuesta objetiva con la pauta posológica elegida entre 2 posibles pautas posológicas (Pauta 1: dosis de 10 mg, 7 días con medicación / 7 días de descanso; y pauta 2: dosis de 6 mg, 21 días con medicación / 7 días de descanso) en pacientes con cánceres uroteliales metastásicos o quirúrgicamente irresecables que presenten alteraciones genómicas específicas del FGFR. |
|
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 |
Los objetivos secundarios del estudio son: *Evaluar la tasa de respuesta objetiva en pacientes resistentes a la quimioterapia. *Evaluar la supervivencia libre de progresión (SSP), la duración de la respuesta y la supervivencia global en todos los pacientes y en los pacientes resistentes a la quimioterapia. *Evaluar la tasa de respuesta en subgrupos con biomarcadores específicos (translocaciones frente a mutaciones). *Evaluar la seguridad y la farmacocinética de JNJ-42756493 en las 2 pautas posológicas. |
|
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 |
- Deben tener confirmación histológica de cancer urotelial metastásico o quirúrgicamente irresecable. Se aceptan componentes menores de variantes histológicas tales como la diferenciación glandular o escamosa, o evolución a fenotipos más agresivos como carcinoma sarcomatoide o cambio micropapilar. - En la selección, deben tener enfermedad medible de acuerdo a los Criterios de Evaluación de Respuesta en Tumores Sólidos (RECIST, versión 1.1). - Deben tener un estado funcional del ?Eastern Cooperative Oncology Group? (ECOG) de 0, 1, o 2 - Deben tener una función medular, hepática y renal adecuada, como se describe en el protocolo. - Prueba de embarazo negativa (beta gonadotropina coriónica humana [b-hCG] en orina o suero) en el momento de la selección para mujeres en edad fértil y sexualmente activas. |
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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) |
- Haber recibido quimioterapia, terapias dirigidas, radioterapia definitiva, inmunoterapia o tratamiento con un fármaco antitumoral en investigación en las 2 semanas previas (en el caso de nitrosureas y mitomicina C, en las 6 semanas previas) a la primera administración del fármaco del estudio. Se permiten terapia con radiación paliativa localizada (pero no debe incluir radiación en la lesión diana) y tratamiento actual con bifosfonatos y denosumab. - Tener persistentes niveles de fosfato por encima del límite superior de normalidad durante la selección (durante los 14 días previos al tratamiento del Ciclo 1 Día 1), a pesar del manejo médico. - Tener o haber tenido enfermedad cardiovascular no-controlada. - Mujeres embarazadas o que estén amamantando, o que tengan planeado quedarse embarazadas durante los tres meses siguientes a haber recibido la última dosis del fármaco del estudio. Hombres que tengan planeado ser padres durante el estudio o en los 5 meses siguientes a haber tomado la última dosis del fármaco del estudio. - No haberse recuperado de una toxicidad reversible debida a un tratamiento antitumoral previo (excepto toxicidades que no sean clínicamente significativas tales como alopecia, decoloración de la piel, o neuropatía Grado 1). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Participants with Best Overall Response |
Porcentaje de sujetos con la mejor respuesta global. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
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. Supervivencia libre de progresión. 2. Duración de la respuesta. 3. Supervivencia global. 4. Número de Sujetos con Eventos Adversos (AEs) y Eventos Adversos Serios (SAEs). 5. Análisis de biomarcadores. 6. Concentración plasmática de JNJ 42756493. 7. Aclaramiento plasmático de JNJ 42756493. 8. Volumen de distribución de JNJ 42756493. |
|
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) |
1/2. Desde la fecha de la administración de la primera dosis del fármaco del estudio hasta progresión de la enfermedad o muerte medida hasta el último análisis de eficacia para la progresión de la enfermedad (aproximadamente 3 años y 9 meses). 3. Desde la fecha de la administración de la primera dosis del fármaco del estudio hasta la muerte (hasta 3 años y 9 meses). 4. Desde la selección hasta el fin de estudio (aproximadamente 3 años y 9 meses). 5/6/7/8. Desde el momento basal hasta el fin de estudio (aproximadamente 3 años y 9 meses). |
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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) | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
A different dosage of the same product |
|
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 | 9 |
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
|
The end of study is defined as approximately 12 months after last subject is enrolled or anytime the Sponsor terminates the study. |
|
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |