E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
colorectal adenocarcinoma. metastatic pancreatic adenocarcinoma melanoma |
adenocarcinoma colorrectal adenocarcinoma pancreático metastásico melanoma |
|
E.1.1.1 | Medical condition in easily understood language |
colorectal adenocarcinoma pancreatic adenocarcinoma melanoma |
adenocarcinoma colorrectal adenocarcinoma pancreático melanoma |
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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 | LLT |
E.1.2 | Classification code | 10033599 |
E.1.2 | Term | Pancreatic adenocarcinoma metastatic |
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 | 10053571 |
E.1.2 | Term | Melanoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 | 10052360 |
E.1.2 | Term | Colorectal adenocarcinoma |
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 |
Phase Ib: Estimation of Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) by measuring incidence of dose limiting toxicities Phase II: Antitumor activity of MEK162 in combination with AMG 479 by evaluating Objective Response Rate (ORR) in colorectal carcinoma and melanoma and by evaluating Disease Control Rate (DCR) at week 10 in pancreatic carcinoma |
Fase Ib: Estimar la dosis máxima tolerada (MTD) y/o identificar la(s) dosis recomendada(s) para la fase II (RP2Ds) de MEK162 en combinación con AMG 479 (ganitumab) en pacientes con tumores sólidos KRAS y BRAF mutantes mediante evaluación de tosicidades limitantes de dosis. Fase II: Estimar la actividad antitumoral de MEK162 en combinación con AMG 479 (ganitumab) medicante evaluación de tasa de respuesta objetiva (ORR) en carcinoma colorectal y melanoma y medciante evaluación de la Tasa de control de la enfermedad (DCR) en la semana 10 en carcinoma pancreático. |
|
E.2.2 | Secondary objectives of the trial |
1. Phase Ib and II: To evaluate the safety and tolerability of MEK162 and AMG 479 (ganitumab) in combination. 2. Phase Ib and II: To determine single and multiple dose PK profile of MEK162 in combination with AMG 479. 3. Phase Ib: To assess preliminary anti-tumor activity of MEK162 and AMG 479 (ganitumab) in combination 4. Phase II: To further assess the anti-tumor activity of MEK162 and AMG 479 (ganitumab) in all three Phase II populations |
Fase Ib + II: ? Caracterizar la seguridad y tolerabilidad de MEK162 y AMG 479 (ganitumab) en combinación ? Determinar el perfil de PK a dosis únicas y múltiples de MEK162 en combinación con AMG 479 (ganitumab) ? Describir la concentración de AMG 479 (ganitumab) en tiempos únicos Fase Ib: ? Evaluar la actividad anti-tumoral preliminar de MEK162 y AMG 479 (ganitumab) en combinación Fase II: ? Evaluar la actividad anti-tumoral de MEK162 y AMG 479 (ganitumab) en combinación en las tres poblaciones de Fase II |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Patients aged ? 18 years ? Patients with advanced solid tumors (CRC, melanoma) with documented somatic KRAS or BRAFV600 mutations in tumor tissue. Patients with metastatic pancreatic adenocarcinoma may be enrolled irrespectively of KRAS or BRAFV600 mutational status. ? Patients must have relapsed or progressed following standard or patients for whom no standard anticancer therapy exists. ? Measurable disease as determined by RECIST v1.1. World Health Organization (WHO) Performance Status (PS) ? 2. ? Adequate organ function ? Negative serum pregnancy test Other protocol-defined inclusion criteria may apply |
? Pacientes con edad ? 18 años ? Pacientes con tumores sólidos avanzados (CRC, melanoma) histológicamente/citológicamente con mutaciones KRAS o BRAFV600 somáticas en el tejido tumoral. Para los pacientes con adenocarcinoma pancreático metastásico las mutaciones KRAS o BRAFV600 no son necesarias ? Los pacientes deben haber recaído o progresado con la terapia estándar o pacientes para quienes no existe terapia anticáncer estándar ? Enfermedad medible determinado mediante RECIST v1.1. ? Estado de Actividad (PS) ? 2 de la Organización Mundial de la Salud (OMS). ? Función orgánica adecuada ? Prueba de embarazo negativa Otros criterios inclusión que aplicaquen definidos en el protocolo |
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E.4 | Principal exclusion criteria |
? Prior therapy with MEK- or IGF-1R- inhibitor ? History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or retinal degenerative disease ? Patients with known history of severe infusion reactions to monoclonal antibodies ? Patients with primary CNS tumor or CNS tumor involvement ? History of thromboembolic event requiring full-dose anticoagulation therapy ? Clinically significant cardiac disease ? History of another malignancy within 2 years ? Pregnant or nursing (lactating) women Other protocol-defined exclusion criteria may apply |
? Terapia previa con inhibidor MEK o IGF-1R. ? Antecedentes o evidencia actual de retinopatía central serosa (RCS), oclusión venosa de la retina (OVR) o enfermedad degenerativa de la retina ? Pacientes con antecedentes conocidos de reacciones graves a la infusión con anticuerpos monoclonales. ? Pacientes con tumor del SNC primario o afectación tumoral del SNC ? Antecedentes de acontecimiento tromboembólico que precise terapia anticoagulante ? Enfermedad cardiaca clínicamente significativa ? Antecedentes de otra tumoración en un plazo de 2 años ? Mujeres embarazadas o en periodo de lactancia Otros criterios exclusión que apliquen definidos en el protocolo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase Ib: measuring incidence of dose limiting toxicities in cycle 1. Phase II: Objective Response Rate (ORR) in colorectal carcinoma and melanoma and Disease Control Rate (DCR) at week 10 in pancreatic carcinoma |
Fase Ib: Incidencia de toxicidades limitantes de dosis (DLTs) en el Ciclo 1 Fase II: tasa de respuesta objetiva (ORR) en grupos carcinoma colorrectal y melanoma y Tasa de control de la enfermedad (DCR) en la semana 10 en carcinoma pancreático |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase Ib: Approximately 6 months Phase II: Approximately 24 months |
Fase Ib: Aproximadamente 6 meses Fase II: Aproximadamente 24 meses |
|
E.5.2 | Secondary end point(s) |
1. Phase Ib and II: Evaluating the adverse events, serious adverse events, changes in hematology and chemistry values, vital signs, ECGs; dose interruptions, reductions and dose intensity 2. Phase Ib and II: Measuring time vs. plasma concentrations and basic PK parameters of MEK162 3. Phase Ib: Evaluating the Overall Response Rate (ORR), Duration of Response (DOR) and Progression Free Survival (PFS) 4. Phase II:Evaluating the Duration of Response (DOR), Progression Free Survival (PFS), and Overall Survival (OS) in all phase II patients and by evaluating Disease Control Rate (DCR) for colorectal carcinoma and melanoma; Overall Response Rate (ORR) for pancreatic carcinoma patients |
1.Fase Ib + II: Acontecimientos adversos, acontecimientos adversos graves, cambios en los valores de hematología y bioquímica, constantes vitales, ECGs 2.Fase Ib + II:Tiempo frente a concentración plasmática, parámetros básicos de PK de MEK162 3.Fase Ib: ORR, Duración de la respuesta (DOR), Supervivencia Sin Progresión (PFS) 4. Fase II: Duración de Respuesta (DOR) Supervivencia Libre de Progresión (PFS) y Supervivencia Global (OS) en todos pacientes de las Fase II y evaluación de la Tasa de control de la enfermedad (DCR) en pacientes con carcinoma colorrectal y melanoma: Tasa de respuesta global (ORR) en pacientes con carcinoma pancreático |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Phase Ib: Approximately 6 months ;Phase II: Approximately 24 months 2. Phase Ib: Approximately 6 months ;Phase II: Approximately 24 months 3. Approximately 6 months 4. Approximately 24 months |
1. Fase Ib: Aproximadamente 6 meses;Fase II: Aproximadamente 24 meses 2. Fase Ib: Aproximadamente 6 meses;Fase II: Aproximadamente 24 meses 3. Aproximadamente 6 meses 4. Aproximadamente 24 meses |
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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 | 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 | 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 |
Dose escalation study of MEK162 and AMG 479 in patients with selected solid tumors |
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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.8.3 |
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 | 6 |
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 |
Australia |
Belgium |
Canada |
France |
Germany |
Italy |
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
|
End of study will be upon completion of the follow-up period of the last patient treated with the combination of MEK162 and AMG 479 (ganitumab). |
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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 |