E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Virus-associated tumors |
Tumores asociados a infecciones virales |
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E.1.1.1 | Medical condition in easily understood language |
Virus-associated tumors |
Tumores asociados a infecciones virales |
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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 | 10017758 |
E.1.2 | Term | Gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008229 |
E.1.2 | Term | Cervical cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10046885 |
E.1.2 | Term | Vaginal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10061306 |
E.1.2 | Term | Nasopharyngeal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047777 |
E.1.2 | Term | Vulvar cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064025 |
E.1.2 | Term | Merkel 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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this study to investigate the safety and efficacy of using nivolumab to treat subjects who have virus-associated tumors. Certain viruses that infect human cells have been known to play a role in tumor formation and growth. This study will investigate the effects of the study drug nivolumab in human subjects who have the following types of tumors: Epstein Barr Virus (EBV) positive gastric cancer; EBV positive nasopharyngeal cancer (NPC); Human Papilloma Virus (HPV) positive cervical, vaginal, vulvar cancer; HPV positive squamous cell cancer of the head and neck (SCCHN); and Polyomavirus positive merkel cell cancer. |
El objetivo de este ensayo es investigar la seguridad y tolerabilidad de la administración de Nivolumab para el tratamiento de sujetos que tienen tumores asociados a infecciones virales. Se conoce que ciertos virus que infectan las células humanas juegan un papel en la formación y crecimiento del tumor. Este ensayo investigará el efecto de Nivolumab en los sujetos que tienen los siguientes tipos tumorales: ?Cáncer gástrico positivo al Virus de Epstein Barr (VEB) ?Cáncer nasofaríngeo positivo al Virus de Epstein Barr (VEB) ?Cáncer cervical positivo al Virus del Papiloma Humano (VPH) ?Cáncer vaginal positivo al Virus del Papiloma Humano (VPH) ?Cáncer vulvar positivo al Virus del Papiloma Humano (VPH) ?Cáncer escamoso de cabeza y cuello (CECC) positivo al Virus del papiloma Humano (VPH) ?Cáncer de células de Merkel positivo al poliomavirus |
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E.2.2 | Secondary objectives of the trial |
-To determine the percent change from baseline of immune cells and the percent change from baseline of select immune activation/inhibitory molecules of viral specific T cells in tumor specific subsets of nivolumab treated subjects. -To evaluate the progression-free survival and overall survival in subjects with nivolumab monotherapy. |
Determinar el cambio porcentual respecto al momento basal de las células inmunitarias y el cambio porcentual respecto al momento basal de moléculas seleccionadas de activación/inhibición de linfocitos T específicos del virus en subgrupos específicos de tumores en sujetos tratados con Nivolumab. Evaluar la supervivencia libre de progresión y la supervivencia global en sujetos con Nivolumab en monoterapia. |
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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 |
Pharmacogenetics Blood Sample Amendment 01 dated 29-Apr-2015 The objective of this Amendment is to permit the collection and storage of blood Choice Placeholdersamples for use in future exploratory pharmacogenetic research. Bristol-Myers Squibb will use DNA obtained from the blood sample and health information collected from the main clinical trial, CA209358 to study the association between genetic variation and drug response. Bristol-Myers Squibb may also use the DNA to study the causes and further progression of virus-positive and virus-negative solid tumor samples from this study may also be used in conjunction with pharmacogenetic research results from other clinical studies to accomplish this objective. |
Enmienda 01 de 29 de abril de 2015 para la obtención de muestras de sangre para estudios de farmacogenética. El objetivo de esta enmienda es permitir la recogida y almacenamiento de muestras de sangre para futuras investigaciones farmacogenéticas exploratorias. BMS utilizará el ADN obtenido de las muestras de sangre y la información de salud recogida del ensayo principal CA209-358 para estudiar la asociación entre variación genética y respuesta al medicamento.BMS, también utilizará el ADN para estudiar las causas y la progresión posterior en de tumores sólidos asociados o no a infecciones virales y también se usarán junto con otros resultados de investigaciones farmacogenéticas de otros ensayos clínicos para cumplir este objetivo. |
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E.3 | Principal inclusion criteria |
-Histopathologic confirmation of the following tumor types (please refer to protocol for full details pertaining to eligible tumor types): ? Merkel Cell Carcinoma ? Gastric or Gastro-Esophageal junction carcinoma ? Nasopharyngeal Carcinoma ? Squamous cell carcinoma of the cervix, vagina, or vulva ? Squamous cell carcinoma of the Head and Neck -Measurable disease by CT or MRI -Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 -Subject willing to comply to provide tumor tissue (archival or fresh biopsy specimen) -Men and women of age 18 or older. |
Confirmación histopatológica de los siguientes tipos tumorales (consultar el protocolo paraa todos los detalles de los tipos de tumores elegibles) Carcinoma de células de Merkel Carcinoma gástrico o de la unión gastroesofágica Carcinoma nasofaríngeo Carcinoma escamoso de cérvix, vagina o vulva Carcinoma escamoso de cabeza y cuello Enfermedad medible mediante TC o RM Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 ó 1 Varones y mujeres de 18 años o mayores Sujeto dispuesto a proporcionar tejido tumoral (muestra de archivo o reciente) |
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E.4 | Principal exclusion criteria |
-Active brain metastases or leptomeningeal metastases -Subjects with active, known or suspected autoimmune disease -Subjects with a condition requiring systemic treatment with either corticosteroids -Subjects with hepatitis;Subjects with HIV -Pregnant or breastfeeding women |
Metástasis cerebrales activas o metástasis leptomeníngeas. Sujetos con enfermedad autoinmune activa, conocida o sospechada. Sujetos con un problema que exija tratamiento sistémico con corticosteroides Sujetos con Hepatitis Sujetos con VIH Mujeres embarazadas o en período de lactancia |
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E.5 End points |
E.5.1 | Primary end point(s) |
-Safety: The proportion of subjects in the neoadjuvant cohort with surgery delayed > 4 weeks due to a drug-related AE. -Efficacy: The investigator-assessed objective response rate (ORR) of nivolumab monotherapy in subjects in the recurrent/metastatic cohort. |
Seguridad: La proporción de sujetos en la cohorte neoadyuvante con retraso en la cirugía > 4 semanas debido a debido a un AA relacionado con el medicamento para cada tipo tumoral. Eficacia: la Tasa de Respuesta Objetiva (TRO), evaluada por el investigador de nivolumab en monoterapia en sujetos de la Cohorte recurrente/metastásica |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-Safety: Contingent on enrollment. -Efficacy: ORR 6 months after the last patient receives their first dose |
Seguridad: Contingente en el reclutamiento Eficacia: TRO 6 meses desppués de queel último paciente reciba su primera dosis. |
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E.5.2 | Secondary end point(s) |
-To determine the percent change from baseline of immune cells and the percent change from baseline of select immune activation/inhibitory molecules of viral specific T cells in tumor specific subsets of nivolumab treated subjects. -To evaluate the progression-free survival and overall survival in subjects with nivolumab monotherapy. |
Determinar el cambio porcentual respecto al momento basal de las células inmunitarias y el cambio porcentual respecto al momento basal de moléculas seleccionadas de activación/inhibición de linfocitos T específicos del virus en subgrupos específicos de tumores en sujetos tratados con Nivolumab. Evaluar la supervivencia libre de progresión y la supervivencia global en sujetos con Nivolumab en monoterapia. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Contingent on enrollment. Rate of enrollment will determine timing for analyses. |
Contingente en el reclutamiento. La tasa de reclutamiento determinará el tiempo del análisis |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker Assessments, Outcomes Research Assessments,Immunogenicity Assessments |
Evaluaciones de biomarcadores, evaluaciones de de resultados en salud, y evaluaciones de inmunogenicidad |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase I mainly safety/biomarker study (neoadjuvant cohort) |
Fase I principalmente seguridad/estudio de biomarcador (chorte neoadjuvante) |
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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 | No |
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 | 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 | 1 |
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 | 13 |
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 |
Japan |
Korea, Republic of |
Netherlands |
Spain |
Taiwan |
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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The study will end when survival follow-up has concluded. |
El ensayo terminará cuando concluya el seguimiento de supervivencia |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 17 |