E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with cancers (excluding melanoma and papillary thyroid cancer) harboring BRAF V600 mutations as identified by the routinely performed mutation analysis assays at each individual participating site |
Pacientes con distintas neoplasias (exceptuando melanoma y cáncer papilar tiroideo) portadoras de mutaciones en BRAF V600, identificadas en análisis específicos para la detección de mutaciones, realizados de forma rutinaria en cada centro participante en el estudio |
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E.1.1.1 | Medical condition in easily understood language |
Patients with cancers (excluding melanoma and papillary thyroid cancer) harboring BRAF V600 mutations. |
Pacientes con distintas neoplasias (exceptuando melanoma y cáncer papilar tiroideo) portadoras de mutaciones en BRAF V600 |
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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 | 10061873 |
E.1.2 | Term | Non-small cell lung 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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian 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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast 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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008593 |
E.1.2 | Term | Cholangiocarcinoma |
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate 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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal 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 |
To evaluate the efficacy of vemurafenib in patients with cancers harboring BRAF V600 mutations as response rate (RR) at Week 8 determined by the Investigator using Response Evaluation Criteria In Solid Tumors, Version 1.1 (RECIST, v1.1) or International Myeloma Working Group (IMWG) uniform response criteria and to identify tumor types for further development |
Evaluar la eficacia de vemurafenib en pacientes con cánceres portadores de mutaciones en BRAF V600 basándose en el índice de respuesta (IR) alcanzado en la semana 8, que será determinado por el investigador utilizando los Criterios de Evaluación de la Respuesta en Tumores Sólidos, Versión 1.1 (RECIST, v1.1) o los criterios de respuesta uniforme del International Myeloma Working Group (IMWG), e identificar tipos de tumores para el futuro desarrollo clínico |
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E.2.2 | Secondary objectives of the trial |
· To evaluate the safety and tolerability of vemurafenib in this patient population. · To evaluate in solid tumors and multiple myeloma (MM) overall response rate (ORR), clinical benefit rate (Clinical response (CR) or Stringent Complete Response (sCR)), partial response (PR) or very good partial response (VGPR) and stable disease [SD]) of vemurafenib, duration of response (DOR), time to response, time to tumor progression (TTP), progression free survival (PFS) and overall survival (OS). |
?Evaluar la seguridad y la tolerancia de vemurafenib en esta población de pacientes. ?Evaluar, en pacientes con tumores sólidos y mieloma múltiple (MM), el índice de respuesta global (IRG), el índice de beneficio clínico [Respuesta clínica (RC) o Respuesta Completa estricta (RCe), Respuesta Parcial (RP) o Respuesta Pacial muy buena (RPMB) y estabilización de la enfermedad (EE)] de vemurafenib, la duración de la respuesta (DR), el tiempo hasta la respuesta, el tiempo hasta la progresión tumoral (TPT), la supervivencia libre de progresión (SLP) y la supervivencia global (SG). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For solid tumor cancer patients only: ?Histologically confirmed cancers (excluding melanoma and papillary thyroid cancer) that harbor a BRAF V600 mutation and are refractory to standard therapy or for which standard or curative therapy does not exist or is not considered appropriate by the Investigator ?Measurable disease according to RECIST, v1.1
For multiple myeloma (MM) patients only: ?Patients with a confirmed diagnosis of MM and harbor a BRAF V600 mutation ?Patients must have received at least one line of prior systemic therapy for the treatment of MM. A line of treatment is sequential treatment without interruption for response and subsequent progression ?Patients treated with local radiotherapy (with or without concomitant exposure to steroids for pain control or management of cord/nerve root compression), two weeks must have lapsed since the last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy should have entry into the Study deferred until the radiotherapy is completed and two weeks have passed since the last date of therapy ?Patients must have relapsed and/or refractory MM with measurable disease, defined as disease that can be measured either by serum or urinary evaluation of the monoclonal component or by serum assay of free light chain (FLC) based on at least one of the following three measurements: oSerum M-protein > 0.5 g/dL oUrine M-protein > 200 mg per 24 hours oInvolved FLC level > 10 mg/dL (> 100 mg/L) provided serum FLC ratio is abnormal
For all patients (solid tumors and MM patients): ?Male or female ? 18 years of age ?Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0?2 ?Adequate hematologic, renal, and liver function |
Sólo para los pacientes con tumores sólidos: 1. Cánceres confirmados histológicamente (exceptuando melanoma y cáncer papilar tiroideo) que son portadores de la mutación BRAF V600 y refractarios a tratamiento estándar o para los que no existe tratamiento estándar o curativo o éste no se considera apropiado, de acuerdo con el criterio del investigador 2. Enfermedad medible, de acuerdo con los criterios RECIST, v1.1 Sólo para los pacientes con mieloma múltiple: 4. Pacientes con diagnóstico confirmado de MM que son portadores de la mutación BRAF V600 5. Los pacientes deben haber recibido previamente al menos una línea de terapia sistémica para el tratamiento del MM. Una línea de terapia se define como el tratamiento secuencial administrado sin interrupción aunque se observe respuesta y posterior progresión de la enfermedad 6. Si los pacientes han recibido radioterapia local (con o sin exposición concomitante a esteroides para el control del dolor o el manejo de la compresión de la médula espinal/raíz nerviosa), deben haber transcurrido dos semanas desde la fecha de la administración de la última sesión de radioterapia, que se recomienda que sea en un área limitada. En el caso de los pacientes que requieran radioterapia concomitante, se aplazará su inclusión en el estudio hasta que se haya completado la radioterapia y hayan transcurrido dos semanas desde la fecha de la última sesión de radioterapia 7. Los pacientes deben presentar MM recurrente y/o refractario con enfermedad medible, que se define como aquella que se puede medir, o bien mediante el componente monoclonal en un análisis en suero u orina, o bien por un análisis en suero de los niveles de cadenas ligeras libres (CLL) basándose al menos en una de las tres determinaciones siguientes: a. Proteína M sérica > 0,5 g/dl b. Proteína M urinaria > 200 mg/24 horas c. Niveles de CLL involucrados > 10 mg/dl (> 100 mg/l), siempre que el ratio de FLC en suero sea anormal Para todos los pacientes (tumores sólidos y MM) 9. Mujeres o varones ? 18 años de edad 10. Estado funcional (EF) del Eastern Cooperative Oncology Group (ECOG) 0?2 11. Función hematológica, renal y hepática adecuada |
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E.4 | Principal exclusion criteria |
?Melanoma, papillary thyroid cancer, or hematological malignancies (with the exception of multiple myeloma) ?Uncontrolled concurrent malignancy (early stage or chronic disease is allowed if not requiring active therapy or intervention and is under control) ?For MM, solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia ?Active or untreated CNS metastases. Patients with brain metastasis are eligible if asymptomatic, off corticosteroid therapy and without evidence of disease progression in brain for ? 2 months. ?Concurrent administration of any anti-cancer therapies (e.g., chemotherapy, other targeted therapy, experimental drug, etc.) other than those administered in this study ?Prior treatment with a BRAF or MEK inhibitor (prior sorafenib is allowed) ?Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption. |
Melanoma, cáncer papilar tiroideo o neoplasias hematológicas (exceptuando mieloma múltiple) Neoplasias concurrentes no controladas (está permitida la inclusión de pacientes con enfermedad en estadio inicial o crónica, si ésta no requiere terapia o intervención activa y está controlada) En pacientes con MM, plasmocitoma solitario óseo o extramedular como única evidencia de la discrasia de células plasmáticas Metástasis del SNC activas o no tratadas. Los pacientes con metástasis cerebrales son aptos para participar en el estudio si son asintomáticos, no están recibiendo tratamiento con corticosteroides, y no han manifestado indicios de progresión de la enfermedad a nivel cerebral durante ? 2 meses Administración concomitante de cualquier terapia anticancerosa (p. ej. quimioterapia, otros agentes dirigidos, fármacos en investigación, etc.) que no sea la utilizada en este estudio Tratamiento previo con un inhibidor de BRAF o MEK (está permitida la administración previa de sorafenib) Náuseas y vómitos refractarios, malabsorción, shunt biliar externo o resección intestinal significativa que impediría una absorción adecuada. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the efficacy of vemurafenib in patients with cancers harboring BRAF V600 mutations as response rate (RR) at Week 8 determined by the Investigator using Response Evaluation Criteria In Solid Tumors, Version 1.1 (RECIST, v1.1) or International Myeloma Working Group (IMWG) uniform response criteria and to identify tumor types for further development |
Evaluar la eficacia de vemurafenib en pacientes con cánceres portadores de mutaciones en BRAF V600 basándose en el índice de respuesta (IR) alcanzado en la semana 8, que será determinado por el investigador utilizando los Criterios de Evaluación de la Respuesta en Tumores Sólidos, Versión 1.1 (RECIST, v1.1) o los criterios de respuesta uniforme del International Myeloma Working Group (IMWG), e identificar tipos de tumores para el futuro desarrollo clínico |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 8 of vemurafenib treatment |
Semana 8 de tratamiento de vemurafenib |
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E.5.2 | Secondary end point(s) |
To evaluate the safety and tolerability of vemurafenib in patients with cancers harboring BRAF V600 mutations. To evaluate in solid tumors and multiple myeloma (MM) overall response rate (ORR), clinical benefit rate (CR (or sCR), PR (or VGPR)) and stable disease [SD]),of vemurafenib, duration of response (DOR), time to response, time to tumor progression (TTP), PFS, and overall survival (OS). |
?Evaluar la seguridad y la tolerancia de vemurafenib en esta población de pacientes. ?Evaluar, en pacientes con tumores sólidos y mieloma múltiple (MM), el índice de respuesta global (IRG), el índice de beneficio clínico [Respuesta clínica (RC) o Respuesta Completa estricta (RCe), Respuesta Parcial (RP) o Respuesta Pacial muy buena (RPMB) y estabilización de la enfermedad (EE)] de vemurafenib, la duración de la respuesta (DR), el tiempo hasta la respuesta, el tiempo hasta la progresión tumoral (TPT), la supervivencia libre de progresión (SLP) y la supervivencia global (SG). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Incidence of adverse events. Overall Response Rate / Tumor assessments according to RECIST Criteria 1 (RECIST, v1.1) or International Myeloma Working Group (IMWG) uniform response criteria. |
Incidencia de acontecimiento advesros. Tasa de Respuesta Global / evaluación de acuerdo con los criterios RECIST, v1.1 o los criterios de respuesta uniforme del International Myeloma Working Group (IMWG). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | 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 |
Identify tumor types for further development |
Identificar tipos de tumores para desarrollos posteriores |
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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 | 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 | 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 | 8 |
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 | 7 |
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 |
Germany |
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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The end of study will occur when all patients have been followed for survival for a maximum period of 12 months since last dose of study medication, have died, withdrawn consent, or are lost to follow up, whichever occurs first. |
El estudio terminará cuando se haya realizado un seguimiento de la supervivencia de todos los pacientes durante un máximo de 12 meses después de la administración de la última dosis del fármaco del estudio, hasta que se produzca la muerte, la retirada del consentimiento o la pérdida de seguimiento de los pacientes, dependiendo de lo que ocurra primero. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |