E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Solid Tumors Advanced B-cell NHL |
Tumores sólidos avanzados Linfoma no Hodgkin de células B avanzado |
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E.1.1.1 | Medical condition in easily understood language |
Advanced Solid Tumors Advanced B-cell NHL |
Tumores sólidos avanzados Linfoma no Hodgkin de células B avanzado |
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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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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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 | 10025311 |
E.1.2 | Term | Lymphoma (non-Hodgkin's) |
E.1.2 | System Organ Class | 100000004864 |
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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 purpose of this study is to determine which doses of urelumab and nivolumab are safe and tolerable when they are given together. |
El objetivo de este estuido es determinar qué dosis de urelumab y nivolumab son seguras y tolerables cuando se administran juntas. |
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E.2.2 | Secondary objectives of the trial |
Best Overall Response (BOR) Objective response rate (ORR), Duration of Response (DOR) Progression-free survival rate (PFSR). Pharmacokinetics: Urelumab maximum concentration Cmax,(µg/mL), time to maximum concentration Tmax (hr), Area under the curve AUCTAU (µg.hr/mL), Area under the curve AUCinf (µg.hr/mL), Clearance (L/day), Volume of distribution (Vss), half life (t1/2), and trough concentration Cmin (µg/mL) will be evaluated using non compartmental analysis in all study subjects. Immunogenicity: Occurrence of specific anti-drug antibodies (ADA) to urelumab and nivolumab, ADA status of the subject |
Mejor respuesta global (MRG), tasa de respuestas objetivas (TRO), duración de la respuesta (DdR), supervivencia libre de progresión (SLP). Farmacocinética: Se evaluará la concentración máxima de urelumab Cmax (µg/ml), tiempo hasta la concentración máxima Tmax (h), área bajo la curva AUCTAU (µg.h/ml), área bajo la curva AUCinf (µg.h/ml), aclaramiento (l/día), volumen de distribución (Veq), semivida (t1/2) y concentración en el valle Cmin (µg/ml) usando análisis no compartimentales en todos los sujetos del estudio. Inmunogenicidad: se determinará la aparición de anticuerpos antifármaco (AAF) específicos frente a urelumab y nivolumab y el estaus de AAF de cada sujeto. |
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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 - Number 01 - dated 9-Jul-14 The objective of this Amendment is to permit the collection and storage of blood samples 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, CA186107 to study the association between genetic variation and drug response. |
Enmienda Número 01 de fecha 09-Julio-2014 sobre las muestras de sangre para Farmacogenética: El objetivo de esta enmienda es permitir la recogida y almacenamiento de muestras de sangre para su uso en una futura investigación farmacogenética exploratoria. Bristol-Myers Squibb usará ADN obtenido de muestras de sangre e información de salud recogida del ensayo clínico CA186107 para estudiar la asociación entre variaciones genéticas y la respuesta al fármaco. |
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E.3 | Principal inclusion criteria |
For Dose Escalation: Subjects with any previously treated advanced (metastatic or refractory) solid tumor type and B-cell non-Hodgkin lymphoma except subjects who have primary central nervous system tumors or with central nervous system metastases as the only site of active disease )
For Cohort Expansion: Subjects must have a previously treated advanced solid tumor or B cell non-Hodgkin?s lymphoma to be eligible: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 For certain subjects, willing and able to provide pre-treatment and on-treatment fresh tumor biopsy Women of child-bearing potential and men must use an acceptable method of contraception during treatment and for 23 weeks after treatment for women and 31 weeks for men. |
Para escalada de dosis: Sujetos con cualquier tipo de tumor sólido avanzado previamente tratado (metastásico o refrecatario) y Linfoma no Hodgkin de células B, excepto sujetos con tumores primarios del SNC o con metástasis en el SNC como única localización de enfermedad activa.
Para expansión de cohortes: Los sujetos deben tener un tumor sólido avanzado previamente tratado o Linfoma no Hodgkin de células B para ser elegibles: Estado del ECOG de 0 ó 1. Para ciertos sujetos, deseo y capacidad de proporcionar biopsias de tumor fresco antes y durante el tratamiento. Las mujeres y hombres potencialmente fértiles deben usar un método anticonceptivo aceptable durante el tratamiento y durante 23 semanas después del taratmiento para mujeres y 31 semanas para hombres |
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E.4 | Principal exclusion criteria |
Known central nervous system metastases or central nervous system as the only source of disease Other concomitant malignancies (with some exceptions per protocol) Active, known or suspected autoimmune disease Uncontrolled or significant cardiovascular disease History of hepatitis (B or C) History of active or latent tuberculosis. |
Sujetos con metástasis en el SNC conocidas o con el SNC como única localización de la enfermedad Otros tumores concomitantes (con algunas excepciones, según el protocolo) Enfermedad autoinmunitaria activa, conocida o de sospecha Enfermedad cardiovascular no controlada o significativa. Antecedentes de hepatitis (B o C) Antecedentes de tuberculosis activa o latente |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety as measured by the rate of adverse events (AEs) and Serious Adverse Events (SAEs), is the primary endpoint of this Phase 1/2 study. All subjects who receive at least one (full or partial) dose of urelumab or nivolumab will be evaluated for safety during treatment and for up to 100 days in follow-up. |
El principal criterio de valoración de este estudio fase 1/2 es la seguridad medida por la tasa de acontecimientos adversos (AA) y acontecimientos adversos graves. Se evaluarán todos los sujetos que reciban al menos una dosis (parcial o completa) de urelumab o nivolumab durante el tratamiento y hasta 100 días después del tratamiento para determinar la seguridad. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During treatment and first 100 days after treatment |
Durante el tratamiento y durante 100 días después del tratamiento. |
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E.5.2 | Secondary end point(s) |
Best Overall Response (BOR) Objective response rate (ORR), Duration of Response (DOR) Progression-free survival rate (PFSR). Pharmacokinetics: Urelumab maximum concentration Cmax,(µg/mL), time to maximum concentration Tmax (hr), Area under the curve AUCTAU (µg.hr/mL), Area under the curve AUCinf (µg.hr/mL), Clearance (L/day), Volume of distribution (Vss), half life (t1/2), and trough concentration Cmin (µg/mL) will be evaluated using non compartmental analysis in all study subjects. Immunogenicity: Occurrence of specific anti-drug antibodies (ADA) to urelumab and nivolumab, ADA status of the subject |
Mejor respuesta global (MRG), tasa de respuestas objetivas (TRO), duración de la respuesta (DdR), supervivencia libre de progresión (SLP) Farmacocinética: Se evaluará la concentración máxima de urelumab Cmax (µg/ml), tiempo hasta la concentración máxima Tmax (h), área bajo la curva AUCTAU (µg.h/ml), área bajo la curva AUCinf (µg.h/ml), aclaramiento (l/día), volumen de distribución (Veq), semivida (t1/2) y concentración en el valle Cmin (µg/ml) usando usando análisis no compartimentales en todos los sujetos del estudio. Inmunogenicidad: se determinará la aparición de anticuerpos antifármaco (AAF) específicos frente a urelumab y nivolumab y el estaus de AAF de cada sujeto. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
BOR, ORR, DOR, PFS: Every 8 weeks for Cycle 1 through Cycle 12 then every 12 weeks thereafter for approximately 2 years Pharmacokinetics:Time Frame: Cycles 1, 2, 3, 4, 6, 8, 10, 12, and followup Days up to 100 days Immunogenicity: Time Frame: Cycles 1 ,2, 3, 4, 6, 8, 10, 12, and followup Days up to 100 days |
MRG, TRO, DdR, SLP: cada 8 semanas del Ciclo 1 al 12 y luego cada 12 semanas durante aproximadamente 2 años. Farmacocinética: Ciclos 1, 2, 3, 4, 6, 8, 10, 12, y seguimiento hasta 100 días después Inmunogenicidad: Ciclos 1 ,2, 3, 4, 6, 8, 10, 12, y seguimiento hasta 100 días después . |
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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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 |
A Phase 1/2 Dose Escalation and Cohort Expansion Study |
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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 | No |
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Germany |
Netherlands |
Spain |
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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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 | 1 |
E.8.9.1 | In the Member State concerned days | 6 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 6 |