E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic nasopharyngeal carcinoma |
Carcinoma nasofaríngeo (CNF) localmente avanzado o metastásico |
|
E.1.1.1 | Medical condition in easily understood language |
Cancer in the area behind the nose and above the back of the throat that has come back after receiving standard treatment |
Cáncer en el área detrás de la nariz y por encima de la parte posterior de la garganta que ha vuelto a aparecer después de recibir el tratamiento estándar |
|
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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028793 |
E.1.2 | Term | Nasopharyngeal carcinoma |
E.1.2 | System Organ Class | 100000004864 |
|
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 evaluate the efficacy of CC-486 in patients with nasopharyngeal carcinoma (NPC) |
Evaluar la eficacia de CC-486 en sujetos con CNF. |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate safety in all patients - To evaluate pharmacokinetics of CC-486 in a subset of patients of Asian-Pacific Island ethnicity |
Evaluar la seguridad en todos los sujetos Evaluar la farmacocinética (FC) de CC-486 en un subgrupo de sujetos del grupo étnico con ascendencia asiática y de las islas del Pacífico |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- Pharmacokinetic sample collection in a subset of enrolled patients of Asian-Pacific Island ethnicity - Biomarker samples collection (stage I of the study as per protocol) |
- Recogida de muestras farmacocinéticas en un subgrupo de sujetos del grupo étnico con ascendencia asiática y de las islas del Pacífico - Recogidas de muestras de biomarcadores (etapa I del estudio según protocolo) |
|
E.3 | Principal inclusion criteria |
- Age = or > 18 years. - Histological or cytological diagnosis of undifferentiated or poorly differentiated nasopharyngeal carcinoma that is locally advanced or metastatic. - Disease progression either clinically or radiographically after 1 to 2 previous regimens. - Patient has received a platinum containing regimen. - Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. - Radiographically-documented measurable disease. - Adequate organ and bone marrow functions. - Willingness to follow pregnancy precautions. |
- Edad mínima de 18 años en el momento de firmar el documento de consentimiento informado. - Diagnóstico histológico o citológico de carcinoma nasofaríngeo indiferenciado o poco diferenciado que esté localmente avanzado o sea metastásico - Progresión clínica o radiológica de la enfermedad después de 1 o 2 tratamientos previos - Recepción previa de un tratamiento con platino. - Estado funcional del ECOG de 0 a 2 - Enfermedad mensurable documentada radiológicamente - Funciones orgánicas y medulares adecuadas - Disposición para cumplir con las precauciones de embarazo |
|
E.4 | Principal exclusion criteria |
- History of, or current brain metastasis. - Any other malignancy within 5 years prior to randomization, with the exception of adequately treated in situ carcinoma of the cervix, uteri, or nonmelanomatous skin cancer (all treatment of which should have been completed 6 months prior to enrollment), in situ squamous cell carcinoma of the breast, or incidental prostate cancer - Previous treatment with azacitidine (any formulation), decitabine, or any other hypomethylating agent. - Impaired ability to swallow oral medication. - Persistent diarrhea or malabsorption. - Major surgery within 14 days prior to starting investigational product or has not recovered from major side effects. - Another investigational therapy within 28 days or 5 half lives of randomization/enrollment, whichever is shorter. - Patient has not recovered from the acute toxic effects of prior anticancer therapy, radiation, or major surgery/significant trauma. - Radiotherapy < or = 4 weeks or limited field radiation for palliation < or = 2 weeks prior to starting with the investigational product. - Any condition that places the patient at unacceptable risk if he/she were to participate in the study or that confounds the ability to interpret data from the study. |
- Antecedentes o presencia de metástasis cerebrales - Presencia de cualquier otra neoplasia maligna en los 5 años previos a la aleatorización, a excepción de un carcinoma in situ de cuello uterino, cáncer de útero o cáncer de piel distinto del melanoma debidamente tratado (todo el tratamiento tendrá que haberse completado 6 meses antes de la inclusión), carcinoma epidermoide in situ de mama o cáncer de próstata incidental - Tratamiento previo con azacitidina (cualquier formulación), decitabina u otro fármaco hipometilante. - Alteración de la capacidad de tragar medicación oral - Presencia de diarrea o malabsorción persistente - Práctica de una intervención de cirugía mayor en los 14 días previos al inicio del tratamiento con el PEI o ausencia de recuperación de efectos secundarios importantes - Recepción de otro tratamiento en investigación en los 28 días previos a la aleatorización/inclusión, o el equivalente a 5 semividas, lo que suponga menos tiempo - Ausencia de recuperación de los efectos tóxicos agudos de un tratamiento antineoplásico o radioterapia previa o de una intervención de cirugía mayor o traumatismo importante - Recepción de radioterapia <= 4 semanas o de radioterapia de campo limitado con fines paliativos <= 2 semanas antes de empezar a tomar el PEI - Presencia de cualquier situación que entrañaría un riesgo inaceptable para el sujeto en caso de que participara en el estudio o que altere la capacidad de interpretar los datos del estudio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Overall response rate (ORR) - Progression-free survival (PFS) |
- Tasa de Respuesta Global (TRG) - Supervivencia Libre de Progresión (SLP) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- ORR and PFS: at screening within 28 days before the start of the Investigational Product and after that every 6 weeks (+- 5 days) from Cycle 1 Day 1, for the first three tumor evaluations and then every 9 weeks until disease progression or start of a new anticancer treatment, or withdrawal of consent |
- TRG y SLP: en el screening dentro de los 28 días antes del inicio del producto en investigación y después de eso cada 6 semanas (+- 5 días) desde el día 1 del ciclo 1 durante las tres primeras evaluaciones del tumor y, posteriormente, cada 9 semanas hasta que se produzca progresión de la enfermedad, inicio de un nuevo tratamiento antineoplásico o retirada del consentimiento |
|
E.5.2 | Secondary end point(s) |
- Overall survival (OS) - Safety - Pharmacokinetics (PK) in a subset of patients of Asian-Pacific Island ethnicity |
- Supervivencia Global (SG) - Seguridad - Farmacocinética en un subgrupo de sujetos del grupo étnico con ascendencia asiática y de las islas del Pacífico |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- OS: continuously during the trial and every 8 weeks (+/- 5 days) in the Follow-up Period - Safety: continuously starting after informed consent signature, until 28 days after treatment discontinuation - PK in a subset of patients of Asian-Pacific Island ethnicity: On each PK day prior to each dose administration and afterwards at 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, and 8h post-dose |
- SG: continuamente durante el ensayo y cada 8 semanas (+- 5 días) en el periodo de seguimiento - Seguridad: continuamente comenzando después de la firma del consentimiento informado, hasta 28 días después de la interrupción del tratamiento - Farmacocinética en un subgrupo de sujetos del grupo étnico con ascendencia asiática y de las islas del Pacífico: en cada día de FC antes de cada administración de la dosis y después a 0,25h, 0,5h, 1h, 1,5h, 2h, 2,5h, 3h, 3,5h, 4h, 6h, and 8h después de la dosis |
|
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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
Canada |
France |
Greece |
Hong Kong |
Italy |
Romania |
Singapore |
Spain |
Taiwan |
Tunisia |
United States |
|
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
|
Either LVLS or the date of receipt of the last data point from the last patient that is required for primary, secondary, and/or exploratory analysis and/or the Statistical Analysis Plan, whichever is the later date. |
El final del estudio se define como la fecha de la última visita del último sujeto que complete el estudio o la fecha de recepción de los últimos datos del último sujeto que sean necesarios para los análisis principales, secundarios o exploratorios, según lo especificado de antemano en el protocolo o el plan de análisis estadístico, la que sea más tardía. |
|
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 | 0 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |