E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IIIb/IV Non-Squamous Non Small-Cell Lung Cancer |
Cáncer de pulmón no microcítico no epidermoide en estadio IIIb/IV |
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E.1.1.1 | Medical condition in easily understood language |
late-stage non-squamous non-small-cell lung cancer |
Cáncer de pulmón no microcítico no epidermoide en estadio 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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
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 compare the OS of patients with stage IIIb/IV non-squamous NSCLC receiving second-line treatment with bavituximab plus docetaxel or placebo plus docetaxel |
Comparar la supervivencia global (SG) en pacientes con cáncer de pulmón no microcítico (CPNM) no epidermoide en estadio IIIb/IV que reciban tratamiento de segunda línea con bavituximab más docetaxel o placebo más docetaxel. |
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E.2.2 | Secondary objectives of the trial |
- To compare PFS and ORR in patients receiving treatment with bavituximab plus docetaxel or placebo plus docetaxel - To compare safety (AEs and clinical laboratory measurements) in patients receiving treatment with bavituximab plus docetaxel or placebo plus docetaxel |
- Comparar la supervivencia sin progressión (SSP) y la tasa de respuesta global (TRG) en pacientes tratados con bavituximab más docetaxel o placebo más docetaxel. - Comparar la seguridad (acontecimientos adversos (AA) y determinaciones de laboratorio clínico) en pacientes tratados con bavituximab más docetaxel o placebo más docetaxel. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Men and women at least 18 years of age - Histologically or cytologically confirmed and documented stage IIIb/IV non-squamous NSCLC according to the American Joint Committee on Cancer Staging Manual, 7th Edition - Radiographic disease recurrence or progression during or after front-line, platinum-based doublet chemotherapy. For patients with known EGFR-activating mutations or ALK translocations, appropriate targeted treatment should have been used. Mutation testing is not required - ECOG performance status of 0 or 1 - Adequate hematologic, renal, and hepatic function |
- Varón o mujer con una edad mínima de 18 años. - CPNM no epidermoide en estadio IIIb/IV confirmado histológica o citológicamente y documentado conforme al Manual de estadificación del cáncer del American Joint Committee (7ª edición) - Recidiva o progresión radiológica de la enfermedad durante o después del tratamiento de primera línea con un doblete de quimioterapia a base de platino. Para pacientes con mutaciones activadoras de receptor del factor de crecimiento epidérmico (EGFR) o translocaciones de cinasa del linfoma anaplásico (ALK) conocidas deberán haber presentado progresión después de un tratamiento dirigido apropiado. No es necesario un test de mutación. - Estado funcional del ECOG de 0 o 1. - Función hematológica, renal y hepatica adecuada. |
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E.4 | Principal exclusion criteria |
- Squamous, small-cell, carcinoid, adenosquamous, large-cell neuroendocrine, or mixed histology containing small-cell or squamous cell - Known history of bleeding disorders, eg, von Willebrand disease or hemophilia - Cavitary tumors or tumors invading or abutting large blood vessels - Clinically significant bleeding such as gross hematuria, GI bleeding, and hemoptysis within 6 months of screening - Thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, arterial thrombosis) within 6 months of screening - Grade 2 or higher peripheral neuropathy |
- Histología epidermoide, microcítica, carcinoide, adenoepidermoide, neuroendocrina de células grandes o mixta con componentes microcíticos o epidermoides. - Antecedentes conocidos de diátesis hemorrágica. Por ejemplo, enfermedad de Von Willebrand o hemofilia. - Tumores cavitados o que invaden o lindan con grandes vasos sanguíneos. - Hemorragia clínicamente significativa, por ejemplo hematuria macroscópica, hemorragia digestiva y hemoptisis, en los 6 meses previos a la selección - Episodios tromboembólicos (por ejemplo, trombosis venosa profunda, embolia pulmonar o trombosis arterial) en los 6 meses previos a la selección. - Neuropatía periférica de grado 2 o superior |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is OS, defined as the number of days from randomization until death, regardless of cause. |
El criterio de valoración principal será la SG, definida como el número de días transcurridos entre la aleatorización y la muerte, con independencia de la causa. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Endpoints are evaluated at each scheduled visit (please refer to Protocol section 6) |
El criterio de valoración principal será evaluado en cada visita programada (refiéranse a la sección 6 del protocolo) |
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E.5.2 | Secondary end point(s) |
Efficacy - PFS: number of days from randomization until either death regardless of cause, or radiologically confirmed progressive disease (PD) - ORR: percentage of patients who achieve complete (CR) or partial (PR) response
Tumor assessments for the determination of PFS and ORR will be according to modified RECIST 1.1 as secondary endpoints. Key modifications of the RECIST 1.1 criteria will include: - Selection of up to 10 target lesions, 5 per organ - New non-nodal lesions < 1 cm are considered equivocal. New nodes >= 1 cm but < 1.5 cm in short axis are considered equivocal.
Safety - AEs - laboratory measurements: hematology (CBC with platelets and differential, biochemistry, and anti-drug antibodies [ADAs]) - vital signs
Population PK - nonlinear mixed effects modeling to evaluate intrinsic (eg, age, gender, race, weight, height, etc.) and extrinsic factors (eg, smoking) that could influence bavituximab exposure and/or response - assessments of exposure-response relationships for safety and efficacy - assessments of the effect of body size on the PK of bavituximab
Exploratory - Immunological studies - Lung Cancer Symptom Scale (LCSS) at baseline, Cycles 3 and 5, every 9 weeks during maintenance therapy, and end of treatment - Potential evidence of radiological pseudoprogression and possible flare effect in patients receiving bavituximab plus docetaxel versus placebo plus docetaxel |
Eficacia - SSP: número de días transcurridos entre la aleatorización y la muerte, con independencia de la causa, o la progresión de la enfermedad (PE) confirmada radiológicamente - TRG: porcentaje de pacientes que logren una respuesta completa (RC) o respueta parcial (RP). Las mediciones tumorales para la determinación del SSP y del TRG se realizarán de acuerdo con los criterios RECIST 1.1 modificados como criterios de valoración secundarios. Las principales modificaciones de los criterios RECIST 1.1 serán: - Selección de un máximo de 10 lesiones diana, 5 por órgano. - Las lesiones extraganglionares nuevas menores 1 cm se consideran dudosas. Los nódulos nuevos mayor o igual a 1 pero menor de 1,5 cm de eje menor se consideran dudosos.
Seguridad - AAs - Parámetros analíticos: hematología (hemograma con recuento de plaquetas y fórmula leucocitaria, bioquímica y anticuerpos contra el fármaco [ACF]). - Constantes vitales
Farmacocinética (FC) poblacional - Modelo de efectos mixtos no lineal para evaluar factores intrínsecos (por ejemplo, edad, sexo, raza, peso, estatura, etc.) y extrínsecos (por ejemplo, tabaquismo) que puedan influir en la exposición o la respuesta a bavituximab. - Evaluaciones de relaciones exposición respuesta en cuanto a eficacia y seguridad. - Evaluaciones del efecto del tamaño corporal sobre la FC de bavituximab.
Exploratorios - Estudios inmunológicos. - Escala de síntomas del cáncer de pulmón (LCSS) en el momento basal, los ciclos 3 y 5, cada 9 semanas durante el tratamiento de mantenimiento y al final del tratamiento. - Posibles indicios de seudoprogresión radiológica y posible efecto de exacerbación en los pacientes que reciban bavituximab más docetaxel en comparación con placebo más docetaxel. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoints are evaluated at each scheduled visit (please refer to Protocol section 6) |
Los criterios de valoración principal serán evaluados en cada visita programada (refiéranse a la sección 6 del protocolo) |
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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 | 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 |
Quality of Life |
Cuestionario de calidad de vida |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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
| 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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 |
Greece |
Italy |
Romania |
Australia |
Germany |
Hungary |
Korea, Republic of |
Spain |
Russian Federation |
Taiwan |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The trial will end when the required number of events has been reached and the database is clean and locked for analysis. Sponsor may stop the study (and/or the study site) for any reason with appropriate notification. |
El ensayo finalizará cuando se haya alcanzado el número de episodios y la base de datos esté limpia y cerrada para su análisis. El promotor podrá interrumpir el estudio (o un centro del estudio) por cualquier motivo, con la notificación correspondiente. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |