E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients with multiple basal cell carcinomas (BCCs). |
Tratamiento de pacientes adultos con carcinomas basocelulares múltiples |
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E.1.1.1 | Medical condition in easily understood language |
Adult patients with multiple basal cell carcinomas. |
Tratamiento de pacientes adultos con carcinomas basocelulares múltiples. |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10004146 |
E.1.2 | Term | Basal 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 assess the relative reduction from baseline (%) in the number of clinically evident BCCs at a defined time point in two different vismodegib regiments. |
Evaluar la reducción relativa (%), respecto al período basal, del número de CBC clínicamente evidentes en la semana 73 (es decir, tras 72 semanas de tratamiento) en los dos regímenes de tratamiento. |
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E.2.2 | Secondary objectives of the trial |
- drop-out rate - relative reduction from baseline in total size of BCCs - recurrence rate - safety - patient reported outcomes |
- Evaluar la tasa de abandonos - Evaluar la reducción relativa (%), respecto al período basal en el total las lesiones CBC diana - La tasa de recurrencia - Seguridad - Evaluar los resultados comunicados por los pacientes (PROs) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Written, signed informed consent, including consent for photographs of target lesions (required) and non-target lesions (optional) - Age ? 18 years - Have multiple BCCs, including patients with Gorlin syndrome, with significant burden of skin disease as manifested by at least 6 clinically evident BCCs at the time of randomization, at least three of which measure 5 mm or more in diameter (target lesions) - Histopathologic confirmation that at least one of the three target lesions is BCC before randomization (2 mm punch biopsy) - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 - Adequate hematopoietic capacity, hepatic and renal function - For women of childbearing potential a negative pregnancy test within 7 days prior to commencement of dosing is required - Women of child-bearing potential must use two methods of acceptable contraception including one highly effective method and a barrier method, as directed by their physician, during treatment and for at least 7 months after completion of study treatment. - For male patients with female partners of childbearing potential, agreement to use a condom, even after a vasectomy, during sexual intercourse with female partners while being treated with vismodegib/placebo, and for 2 months after completion of study treatment - Agreement not to donate blood or blood products during the study and for at least 7 months after completion of study treatment |
1. Firmar el consentimiento informado por escrito, incluyendo el consentimiento para obtener fotografías de las lesiones diana (obligatorias) y las lesiones no diana (opcionales) 2. Tener ? 18 años de edad 3. Presentar CBC múltiples, incluyendo pacientes con síndrome de Gorlin (véanse los criterios diagnósticos en el Anexo 5) con una carga de enfermedad cutánea significativa, evidenciada por lo siguiente: Presencia de un mínimo de 6 CBC clínicamente evidentes en el momento de la randomización, de los cuales al menos tres deben medir ? 5 mm de diámetro (lesiones diana) 4. Debe existir confirmación histopatológica (mediante biopsia por trepanación de 2 mm) de que al menos una de las tres lesiones diana es CBC antes de la randomización 5. Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0, 1 o 2 (véase el Anexo 4) 6. Función hematopoyética, hepática y renal adecuadas. 7. Las mujeres potencialmente fértiles (véase el Anexo 3) deben presentar un resultado negativo en la prueba de embarazo realizada en los 7 días previos al inicio del tratamiento 8. Las mujeres potencialmente fértiles deben utilizar dos métodos anticonceptivos aceptables, que serán prescritos por su médico, incluyendo uno que sea altamente eficaz y un método de barrera (véase también el Anexo 3) durante el tratamiento y, como mínimo, hasta 7 meses después de haber completado el tratamiento del estudio. 9. Los pacientes cuyas parejas femeninas sean potencialmente fértiles deben comprometerse a utilizar preservativos con espermicida, incluso después de una vasectomía, cuando mantengan relaciones sexuales con su pareja mientras están recibiendo tratamiento con vismodegib/placebo y hasta 2 meses después de haber completado el tratamiento del estudio. 10. Los pacientes deben comprometerse a no donar sangre o hemoderivados durante el estudio y, como mínimo, hasta 7 meses después de haber completado el tratamiento del estudio |
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E.4 | Principal exclusion criteria |
- Inability or unwillingness to swallow capsules and to comply with study procedures - Pregnancy or breastfeeding - Any metastatic BCC - Locally advanced BCC lesion that is considered to be inoperable or to have a medical contraindication to surgery in the opinion of a Mohs surgeon, dermatologic surgeon, head and neck surgeon, surgical oncologist, or plastic surgeon. - Recent (i.e., within the past 28 days prior to randomization) or current participation in another experimental drug study - Uncontrolled medical illness, including advanced malignancies, at the discretion of the Investigator - History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications - Any medical or psychological illness or condition preventing adequate consent or ability to comply with the protocol |
1. Incapacidad o falta de disposición para ingerir cápsulas 2. Incapacidad o falta de disposición para cumplir los procedimientos del estudio 3. Embarazo o lactancia 4. Presentar cualquier CBC metastásico 5. Presentar lesiones de CBC localmente avanzado que se consideren inoperables o para las cuales la cirugía esté contraindicada clínicamente (véase más abajo), de acuerdo con la opinión de un cirujano especialista en cirugía de Mohs, dermatología, cabeza y cuello, oncología o cirugía plástica. 6. Participación reciente (es decir, en los 28 días previos a la randomización) o actual en otro estudio con un fármaco experimental 7. Patologías no controladas, incluyendo neoplasias avanzadas, de acuerdo con el criterio del investigador 8. Antecedentes de otras enfermedades, trastornos metabólicos, hallazgos en la exploración física o en las pruebas de laboratorio clínico que proporcionen indicios razonables para sospechar la existencia de una enfermedad o patología para la cual está contraindicado el uso de un fármaco en investigación o que pudiera afectar a la interpretación de los resultados del estudio o suponer para el paciente un riesgo alto de experimentar complicaciones relacionadas con el tratamiento 9. Cualquier enfermedad o trastorno clínico o psicológico que impida al paciente otorgar adecuadamente el consentimiento o que comprometa a su capacidad para cumplir los requisitos del protocolo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Relative reduction from baseline (%) in the number of clinically evident BCCs at a defined time point in two different vismodegib regiments |
La reducción relativa (%) del número de CBC clínicamente evidentes en la semana 73 (end point) en los dos regímenes de tratamiento. |
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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) |
Drop-out rate, relative reduction from baseline in total size of BCCs, recurrence rate, safety, patient reported outcomes |
La tasa de abandonos, la reducción relativa (%), respecto al período basal en el total las lesiones CBC diana, la tasa de recurrencia, la seguridad y los resultados comunicados por los pacientes (PROs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Treatment Phase (Week 9, 17, 25, 33, 41, 49, 57 and 65), Week 73, 85, 97 and 125 |
Fases del tratamiento (semana 9, 17, 25, 33, 41, 49, 57 y 65), semana 73, 85, 97 y 125 |
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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 | 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 |
tolerability |
Tolerabilidad |
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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 | 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 |
Dos regímenes de tratamiento (alternancia de vismodegib y placebo) |
two treatment regimens (alternance of vismodegib and placebo) |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Austria |
Brazil |
Canada |
France |
Germany |
Italy |
Mexico |
Netherlands |
Russian Federation |
Spain |
Switzerland |
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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LPLV (the end of study visit will be performed after 52 weeks of follow-up after completion of the study treatment) |
La visita de terminación del estudio se realizará tras 52 semanas de seguimiento, después de haber completado el tratamiento del estudio. |
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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 | 6 |
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 | 6 |