E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
AKL positive advanced non-small cell lung cancer |
carcinoma de pulmón de célula grande ALK positivo |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced lung cancer |
Cáncer de pulmón avanzado |
|
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 | 10025054 |
E.1.2 | Term | Lung cancer non-small cell stage IIIB |
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 | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 |
Determine the objective response rate (ORR) of ganetespib in subjects with advanced ALK-positive NSCLC |
Determinar la tasa de respuesta objetiva (TRO) del ganetespib en pacientes con CPNM positivo para la cinasa del linfoma anaplásico avanzado. |
|
E.2.2 | Secondary objectives of the trial |
-Determine the overall progression-free survival (PFS), 6-month PFS and 1-year PFS. -Determine duration of response. -Determine the overall survival (OS) and 1-year OS. -Determine the disease control rate (DCR) at weeks 6 and 12. -Determine the change in tumor size (CTS) at weeks 6 and 12. -Evaluate the qualitative and quantitative toxicities associated with ganetespib in subjects with ALK-positive NSCLC. -Evaluate symptom improvement using Functional Assessment of Cancer Therapy Lung (FACT-L) version 4. -Determine the relationship of clinical outcome with relevant biomarkers and genetic changes present in tumor tissues and serum samples. |
-Determinar la supervivencia sin progresión (SSP) total, la SSP a los 6 meses y la SSP al año. -Determinar la duración de la respuesta. -Determinar la supervivencia total (ST) y la supervivencia a un año. -Determinar la tasa de control de la enfermedad (TCE) en las semanas 6 y 12. -Determinar el cambio en el tamaño del tumor (CTT) en las semanas 6 y 12. -Evaluar las toxicidades cualitativas y cuantitativas asociadas con el ganetespib en pacientes con CPNM positivo para la cinasa del linfoma anaplásico. -Evaluar la mejora de los síntomas con la evaluación funcional del tratamiento de cáncer de pulmón (FACT-L), versión 4. -Determinar la relación del resultado clínico con los biomarcadores relevantes y los cambios genéticos presentes en los tejidos tumorales y las muestras de suero. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 Males or females aged 18 years or older 2 Pathological confirmation (by histology or cytology) of advanced NSCLC a. De novo disease (i.e., 0 lines of prior therapy; stage IIIB or IV NSCLC according to the AJCC Cancer Staging Manual 7th Edition 2010 Or b. Recurrent disease with up to 3 lines of prior systemic therapy (i.e., 1-3) 3 Histological confirmation of adenocarcinoma 4 Evidence of a translocation or an inversion event involving the ALK gene locus as determined by either a local or central laboratory, or prior documentation of ALKpositive status by a local laboratory 5 Availability of recent tumor tissue or a minimum of 10 slides of archived tumor tissue is required for ALK rearrangement confirmation testing and evaluating relevant biomarkers. 6 ECOG Performance Status 0 or 1 7 Adequate hematologic, hepatic and renal function (as defined in the protocol) |
1.Hombres o mujeres de 18 años o más 2 Confirmación patológica (mediante histología o citología) de CPNM avanzado a.Enfermedad de novo (es decir, 0 líneas de tratamiento anterior; CPNM de etapa IIIB o IV según el AJCC Cancer Staging Manual 7.ª edición 2010) O b.Enfermedad recurrente con hasta 3 líneas de tratamiento sistémico anterior (es decir, 1 a 3) 3 Confirmación histológica de adenocarcinoma 4 Evidencia de translocación o evento de inversión que involucre el locus génico de la cinasa del linfoma anaplásico según lo determine un laboratorio local o central, o documentación previa del estado positivo para la cinasa del linfoma anaplásico de un laboratorio local 5 Se necesita disponibilidad de tejido tumoral reciente o un mínimo de 10 láminas de tejido tumoral archivado para la prueba de confirmación de reordenación de la cinasa del linfoma anaplásico y la evaluación de los biomarcadores relevantes 6. Resultado de estado 0 o 1 en ECOG 7. Función hematológica, hepática y renal adecuada (tal y como se define en el protocolo) |
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E.4 | Principal exclusion criteria |
1. Prior therapy with crizotinib 2. Prior therapy with other ALK-targeted agents 3. Prior treatment with any Hsp90 inhibitor 4. Known EGFR activating mutation 5. Presence of active or untreated central nervous system (CNS) metastases as determined by magnetic resonance imaging (MRI) or computed tomography (CT) scan performed during screening or individuals who have been treated for CNS metastasis and discontinued the steroid treatment less than 4 weeks prior to Cycle 1 Day 1 6. Active malignancies other than NSCLC within the previous 2 years with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri or basal or squamous cell carcinoma of the skin 7. Known serious cardiac illness (see protocol for details) 8. Prior radiotherapy to the only area of measurable disease 9. Radiotherapy within 2 weeks prior to Cycle 1 Day 1 (related radiotherapy toxicities must be < o = Grade 1) 10. Major surgery (unrelated to NSCLC) within 4 weeks prior to Cycle 1 Day 1 11. Women who are pregnant or lactating 12. Significant weight loss (> o =10% body weight) within the 4 weeks prior to Cycle 1 Day 1 |
1 Tratamiento anterior con crizotinib 2 Tratamiento anterior con otros agentes para la cinasa del linfoma anaplásico 3 Tratamiento anterior con cualquier inhibidor de la Hsp90 4 Mutación conocida de activación del receptor del factor de crecimiento epidérmico 5 Presencia de metástasis del sistema nervioso central (SNC) activa o sin tratar, según lo determine una imagen por resonancia magnética (IRM) o una tomografía computarizada (TC) realizada durante la selección o personas que hayan sido tratadas para la metástasis del SNC y discontinuaron el tratamiento con esteroides menos de 4 semanas antes del ciclo 1 día 1 6 Neoplasias activas que no sean CPNM en los 2 años anteriores con la excepción de un carcinoma in situ biopsiado en cuña tratado del cuello uterino o carcinoma de células basales o escamosas de la piel 7 Afección cardiaca grave conocida (véase el protocolo para más detalles) 8 Radioterapia anterior sólo en el área de la enfermedad mensurable 9 Radioterapia en las últimas 2 semanas antes del ciclo 1 día 1 (las toxicidades relacionadas con la radioterapia deben ser < o = al grado 1) 10 Cirugía mayor (no relacionada con el CPNM) en las 4 semanas antes del ciclo 1 día 1 11 Mujeres embarazadas o en periodo de lactancia 12 Pérdida de peso importante (> o =10 % del peso corporal) en las 4 semanas antes del ciclo 1 día 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective Response Rate (ORR) (the proportion of subjects showing a complete or partial response). |
Tasa de respuesta objetiva (TRO) (proporción de pacientes que alcancen respuesta parcial o completa) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis of ORR will be conducted 3 months after the last subject is enrolled |
El análisis primario de la TRO se llevará a cabo 3 meses tras la inclusión del último sujeto |
|
E.5.2 | Secondary end point(s) |
Progression Free Survival (PFS) Duration of Response (DOR) Overall Survival (OS) Disease Control Rate (DCR) Change in Tumor Size (CTS) Adverse Events Symptom improvement outcome Correlative Biomarker Analyses Laboratory Data Other Safety Parameters |
Supervivencia sin progresión (SSP) Duración de la respuesta (DR) Supervivencia total (ST) Tasa de control de la enfermedad (TCE) Cambio en el tamaño del tumor (CTT) Acontecimientos adversos Mejora de síntomas Análisis correlativo de biomarcadores Datos de laboratorio Otros parámetros de seguridad |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The PFS rate at 6 months and 1 year The OS rate at 1 year DCR is measured at weeks 6 and 12 CTS is measured from baseline to at least 6 weeks (CTS-6) or 12 weeks (CTS-12) |
SSP a los 6 meses y 1 año ST a 1 año TCE a las 6 y 12 semanas CTT desde basal hasta al menos 6 semanas (CTT-6) o 12 semanas (CTT-12) |
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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 | 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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | No |
E.8.1.2 | Open | Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
Bosnia and Herzegovina |
Canada |
Croatia |
France |
Germany |
Serbia |
Spain |
United Kingdom |
United States |
|
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 trial is last survival follow-up of last patients (patients will be followed for survival for up to 3 years) |
El final del ensayo es el último seguimiento de supervivencia del último paciente (se hará seguimiento de supervivencia hasta 3 años) |
|
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 | 10 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |