E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
First-line patients with extensive disease (Stage IV) small-cell lung cancer (SCLC) |
Tratamiento de primera línea en pacientes con cáncer de pulmón microcítico (CPM) en enfermedad avanzada (estadio IV) |
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E.1.1.1 | Medical condition in easily understood language |
Treatment naïve patients with extensive-stage small-cell lung cancer |
Pacientes con cáncer de pulmón microcítico en estadío avanzado que no han recibido tratamiento |
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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 | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041068 |
E.1.2 | Term | Small cell lung cancer extensive stage |
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 assess the efficacy of durvalumab + tremelimumab + EP treatment compared with EP in terms of overall survival (OS) and progression-free survival ( PFS). |
Evaluar la eficacia del tratamiento con durvalumab + tremelimumab + EP en comparación con EP en cuanto a la SG y la SLP. |
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E.2.2 | Secondary objectives of the trial |
1.To further assess the efficacy of durvalumab + tremelimumab + EP treatment compared with EP in terms of ORR, APF6, APF12 and OS 18. 2.To assess the efficacy of durvalumab + EP compared with EP in terms of ORR, PFS, OS, APF6, APF12, and OS18. 3.To assess the efficacy of durvalumab + tremelimumab + EP treatment compared with durvalumab + EP in terms of PFS and OS. 4.To assess the PK of both durvalumab and durvalumab + tremelimumab. 5.To investigate the immunogenicity of durvalumab and durvalumab + tremelimumab. 6.To assess the effect of the treatment on changes in symptoms and health-related QoL using EORTC QLQ-C30 v3 and QLQ-LC13. 7.Safety objective: To assess the safety and tolerability profile of durvalumab and durvalumab + tremelimumab in combination with EP treatment compared with EP. |
1.Evaluar la eficacia del tratamiento con durvalumab + tremelimumab + EP en comparación con EP en cuanto a TRO, VSP6, VSP12 y SG18 2.Evaluar la eficacia de durvalumab + EP en comparación con EP en cuanto a TRO, SLP, SG, VSP6, VSP12 y SG18 3. Evaluar la eficacia del tratamiento con durvalumab + tremelimumab + EP en comparación con durvalumab + EP en cuanto a la SLP y la SG 4. Evaluar la FC tanto de durvalumab como de tremelimumab 5. Investigar la inmunogenia de durvalumab y de durvalumab + tremelimumab. 6. Evaluar el efecto del tratamiento en los síntomas del CPM y la CdV relacionada con la salud utilizando los cuestionarios QLQ-C30 v3 y QLQLC13 de la EORTC. 7. Objetivo de seguridad: Evaluar la seguridad y la tolerabilidad del tratamiento con durvalumab y durvalumab + tremelimumab combinado con EP en comparación con solo EP |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Histologically or cytologically documented extensive disease (American Joint Committee on Cancer Stage IV SCLC [T any, N any, M1 a/b]), including patients with T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan. Brain metastases; must be asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment. 2. Suitable to receive a platinum-based chemotherapy regimen as 1st line treatment. 3. Life expectancy ≥12 weeks at Day 1. 4. ECOG 0 or 1 at enrolment. 5. No prior exposure to immune-mediated therapy excluding therapeutic anticancer vaccines. 6 .Body weight >30 kg. 7. Adequate organ and marrow function. |
1. Pacientes con enfermedad extendida documentada histológica o citológicamente (CPM en estadio IV según el American Joint Committee on Cancer [T cualquiera, N cualquiera, M1 a/b]), incluyendo pacientes con T3-4 debido a múltiples nódulos pulmonares que son demasiado extensos o que tienen el volumen del tumor/nódulo demasiado grande para ser abarcado en una radiación tolerable. Metástasis cerebrales; deben ser asintomáticas o tratadas y estables sin esteroides ni anticonvulsivos durante al menos 1 mes antes de tratamiento del estudio. 2. Pacientes idoneos para recibir el régimen de quimioterapia basada en platino como primera línea de tratamiento. 3. Esperanza de vida >o= a 12 meses en el Día 1 4. ECOG 0 o 1 en el momento de inclusión. 5. No exposición anterior a tratamiento inmune excluyendo tratamiento de vacunas anticancerígenas. 6. Peso >30 kg 7. Función de los órganos y de la medula adecuada. |
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E.4 | Principal exclusion criteria |
1. Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy (except paliative care outside of the chest). 2. Any other concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. 3. History of allogenic organ transplantation. 4. Paraneoplastic syndrome of autoimmune nature, requiring systemic treatment or clinical symptomatology suggesting worsening of PNS 5. Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. 6. History of another primary malignancy 7. Active infection including tuberculosis, HIV, hepatitis B anc C 8. Current or prior use of immunosuppressive medication within 14 days before the first IP dose 9. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control.. 10. Past medical history of interstitial lung disease, drug-induced pneumonitis, or any evidence of clinically active interstitial lung disease. |
1. Antecedentes de radioterapia en el tórax antes del tratamiento sistémico o terapia de radiación en el tórax planeada y consolidada (exceptuando cuidado paliativos fuera del tórax) 2. Cualquier otro tratamiento concurrente como quimioterapia, IP, biológica u hormonal para el tratamiento del cáncer. 3. Antecedentes de trasplantes de órganos halogenados. 4. Síndrome paraneoplásico de naturaleza autoinmune, que requiere tratamiento sistémico o sintomatológico clínico que sugiere un empeoramiento del SNP 5. Enfermedad intercurrente incontrolada o enfermedad psiquiatra/situaciones sociales que podrían limitar la conformidad de los requerimientos del estudio, aumento relevante del riesgo de incidencias de AAs o del compromiso de la habilidad del paciente de dar el consentimiento informado firmado 6. Antecedentes de otro tumor maligno primario 7. Infección activa incluyendo tuberculosis, HIV, hepatitis B y C 8. Uso previo o actual de medicación inmunosupresora dentro de los 14 días antes de la primera dosis del medicamento en investigación 9. Pacientes femeninas que están embarazadas o en lactancia o pacientes masculinos o femeninos con capacidad de reproducirse que no desean utilizar anticonceptivos efectivos. 10. Antecedentes personales de enfermedad pulmonar intersticial, neumonitis inducida por fármacos, o cualquier evidencia de enfermedad pulmonar intersticial clínicamente activa. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Overall survival (OS)- the time from the date of randomization until death due to any cause. 2.Progression free survival (PFS)- the time from the date of randomization until the date of objective disease progression or death. |
1.La supervivencia global (SG)-tiempo desde el día de la aleatorización hasta el fallecimiento debido a cualquier causa. 2.La supervivencia libre de progresión (SLP)-tiempo desde el día de la aleatorización hasta el día fijado de la progresión de la enfermedad o muerte. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. 34 months after the first patient has been randomized 2. 23 months after the first patient has been randomized |
1. 34 meses meses después de la aleatorización del primer paciente. 2. 23 meses meses después de la aleatorización del primer paciente. |
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E.5.2 | Secondary end point(s) |
1.Objective Response Rate (ORR) -the number (%) of patients with at least 1 visit response of CR or PR. 2.Proportion of patients alive and progression free at 6 (APF6) and 12 months (APF12). 3. Proportion of patients alive at 18 months (OS18). |
1.Tasa de respuesta objetiva (TRO)-el número de pacientes (%) con al menos 1 visita de respuesta de RC y RP 2.La proporción de pacientes vivos y sin progresión a los 6 (VSP6) y 12 meses (VSP12) 3.Proporción de pacientes vivos a los 18 meses (SG18) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
23 months after the first patient has been randomized |
23 meses meses después de la aleatorización del primer paciente. |
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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 | Yes |
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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 104 |
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 |
Argentina |
Austria |
Brazil |
Bulgaria |
China |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Poland |
Romania |
Russian Federation |
Slovakia |
Spain |
Taiwan |
Turkey |
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
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The end of the study is defined as the “last visit of the last patient undergoing the study.” |
El final del estudio se define como "la última visita del último sujeto que participe en el estudio" |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 27 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 21 |