E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Small Cell Lung Cancer |
Carcinoma microcítico de pulmón |
|
E.1.1.1 | Medical condition in easily understood language |
Small Cell Lung Cancer |
Carcinoma microcítico de pulmón |
|
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 | 17.0 |
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) |
|
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 |
The overall purpose of the study is to evaluate efficacy and safety of MGN1703 administered twice weekly s.c. as maintenance treatment in patients with extensive disease SCLC who achieved at least PR following platinum-based first-line therapy |
Evaluación de la eficacia y la seguridad de MGN1703 administrado dos veces a la semana por vía subcutánea (s.c.) como tratamiento de mantenimiento en pacientes con carcinoma microcítico de pulmón (CMP) extendido que lograron como mínimo una remisión parcial (RP) después del tratamiento de primera línea basado en platino. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male and female patients with extensive disease SCLC ? 18 years of age receiving first line treatment 2.Histology of SCLC or mixed histology of SCLC if SCLC histology is at least 80% 3.Completion of 4 cycles of first-line therapy with a platinum-based regimen and no other prior chemotherapy 4.Documented evidence of tumor response as assessed by investigators after the first 2 cycles of platinum-based chemotherapy followed by a confirmed PR or CR at the end of fourth cycle by CT or MRI scan 5.Brain metastases are allowed, only after cranial irradiation, if not requiring continuous treatment with steroids or anticonvulsants; 6.ECOG performance status 0 or 1; 7.Adequate organ function with total bilirubin, lactate dehydrogenase [LDH], alkaline phosphatase [AP], gamma glutamyltransferase [GGT], albumin, creatinine, urea, electrolytes, and coagulation parameters ? 1.5 × upper limit of normal (ULN), and with aspartate aminotransferase [AST] and ALT ? 2.5 × ULN in the absence of liver metastases or ? 5.0 × ULN in the presence of liver metastases; 8.Adequate hematological parameters: absolute neutrophil count ? 1.5 × 109/L; platelet count ? 100 × 109/L; leukocyte count ? 3.0 × 109/L; lymphocytes ? 1.0 × 109/L; hemoglobin ? 9.0 g/dL or 5.59 mmol/L; 9.Male patients who have had vasectomy, and female patients who are not of childbearing potential (i.e. who are post-menopausal for at least 24 consecutive months or who have undergone surgical sterilization [hysterectomy, bilateral tubal ligation, or bilateral oophorectomy]). Male and female patients with reproductive potential can be included if they are using an effective means of contraception with a failure rate of less than 1% per year throughout the study, e.g. established use of oral, implanted, or injected hormonal contraceptives; placement of intra-uterine device or intra-uterine system; or use of barrier methods such as condom or diaphragm together with spermicide product; 10.Negative pregnancy test in women of childbearing potential; 11.Signed informed consent form (ICF) |
1. Pacientes de ambos sexos con CMP extendido de ? 18 años de edad que reciben tratamiento de primera línea 2. Histología de CMP o histología mixta si la histología de CMP es como mínimo del 80 % 3. Conclusión de 4 ciclos de tratamiento de primera línea con un régimen basado en platino y ninguna otra quimioterapia anterior 4. Indicios documentados de respuesta tumoral evaluada por los investigadores después de los 2 primeros ciclos de quimioterapia basada en platino seguida de una RP confirmada o una respuesta completa (RC) confirmada al final del cuarto ciclo mediante tomografía axial computerizada (TAC) o resonancia magnética (RMN) 5. Se permiten metástasis cerebrales solo después de radioterapia craneal, si no se requiere tratamiento continuo con esteroides o anticonvulsivos 6. Estado funcional del Grupo Oncológico Cooperativo de la Costa Este (ECOG) de 0 o 1 7. Funcionamiento orgánico adecuado, con niveles de bilirrubina total, deshidrogenasa láctica [LDH], fosfatasa alcalina [FA], gammaglutamil-transferasa [GGT], albúmina, creatinina, urea, electrolitos y coagulación ? 1,5 × límite superior de la normalidad (LSN), y con valores de aspartato aminotransferasa [AST] y alanina aminotransferasa [ALT] ? 2,5 × LSN en ausencia de metástasis hepáticas o ? 5,0 × LSN en presencia de metástasis hepáticas 8. Valores hematológicos adecuados: cifra absoluta de neutrófilos ? 1,5 × 109/l; cifra de trombocitos ? 100 × 109/l; cifra de leucocitos ? 3,0 × 109/l; linfocitos ? 1,0 × 109/l; hemoglobina ? 9,0 g/dl o 5,59 mmol/l 9. Hombres que hayan sido vasectomizados y mujeres que no sean fértiles (esto es, que sean posmenopáusicas por los menos 24 meses consecutivos o que hayan sido esterilizadas quirúrgicamente [histerectomía, ligadura de trompas bilateral u ooforectomía bilateral]). Se pueden incluir pacientes fértiles si utilizan durante el estudio un anticonceptivo eficaz con una tasa de fallo menor al 1% al año, por ejemplo, uso comprobado de anticonceptivos hormonales orales, implantados o inyectados; colocación de un dispositivo intra-uterino o sistema intra-uterino; o uso de métodos de barrera como el preservativo o el diafragma junto con un producto espermicida 10. Prueba de embarazo negativa para mujeres fértiles 11. Formulario de consentimiento informado firmado |
|
E.4 | Principal exclusion criteria |
1.Patients with no evidence of response after 2 cycles of chemotherapy or early response not maintained at Cycle 4; 2.Clinically significant concomitant diseases or conditions, which, in opinion of the investigator, would lead to an unacceptable risk for the patient to participate in the study; 3.Prior or current other malignancy, except adequately treated superficial bladder cancer, basal or squamous cell carcinoma of the skin, or other cancer for which the patient has been disease free for more than 3 years; 4.Active or uncontrolled infections at the time of randomization; 5.Severe anemia requiring repeated blood cells transfusion ; 6.History of autoimmune disease or immune deficiency; 7.Known hypersensitivity to oligonucleotides or excipients of the formulation; 8.Pregnant and/or nursing; 9.Concurrent chronic systemic immune therapy or immunosuppressant medication, including continuous steroid treatment within the last 2 weeks prior to randomization; 10.Use of antibiotic therapy within the last 2 weeks prior to randomization 11.Concurrent use of molecular targeted therapy; 12.Known HIV seropositivity or known active hepatitis B or C infection; 13.Planned major surgery during the study, except for thoracotomy; 14.Participation in another clinical study with other investigational drugs within 14 days prior to randomization; 15.Vaccination within 1 month prior to randomization; 16.Any medical, mental, psychological or psychiatric condition that in the opinion of the investigator would not permit the patient to complete the study or understand the patient information; 17.Presence of drug and/or alcohol abuse |
1. Pacientes sin indicios de respuesta después de 2 ciclos de quimioterapia o respuesta inicial no mantenida en el ciclo 4; 2. Enfermedades concomitantes significativas desde el punto de vista clínico que, en opinión del investigador, pudieran generar un riesgo inaceptable para el paciente si éste participara en el estudio; 3. Otra neoplasia maligna anterior o actual, salvo cáncer de vejiga superficial adecuadamente tratado, carcinoma cutáneo basocelular o espinocelular, u otro carcinoma del que el paciente lleve más de 3 años curado; 4. Infecciones activas o no controladas en el momento de la aleatorización; 5. Anemia grave que requiere transfusiones de sangre repetidas; 6. Antecedentes de enfermedad autoinmunitaria o inmunodeficiencia; 7. Hipersensibilidad conocida a los oligonucleótidos o a los excipientes de la formulación; 8. Mujeres en período de gestación y/o lactancia; 9. Inmunoterapia sistémica de larga duración o medicación inmunosupresora concurrente, incluido el tratamiento continuo con esteroides en las 2 semanas anteriores a la aleatorización; 10. Administración de antibioterapia en las 2 semanas anteriores a la aleatorización; 11. Administración concurrente de terapia molecular dirigida; 12. Seropositividad al VIH conocida o infección activa por virus de hepatitis B o C; 13. Cirugía mayor programada durante el estudio, excepto toracotomía; 14. Participación en otro estudio clínico con otros fármacos experimentales en los 14 días anteriores a la aleatorización; 15. Vacuna 1 mes antes de la aleatorización; 16. Cualquier afección física, mental, psicológica o psiquiátrica que, en opinión del investigador, impediría al paciente terminar el estudio o entender la información para el paciente; 17. Presencia de drogodependencia y/o alcoholismo |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival from the date of randomization |
Supervivencia Global (SG) desde la fecha de aleatorización |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of study |
Fin del estudio |
|
E.5.2 | Secondary end point(s) |
?Overall survival from the start of the first cycle of induction therapy (OS1); ?Progression-free survival from the date of randomization with progression assessed by RECIST 1.1 and irRC; ?Progression-free survival from the start of the first cycle of induction therapy (PFS1) assessed by RECIST 1.1 and irRC; ?Best objective response rate (ORR) with clinical response assessed by RECIST 1.1 and irRC; ?Quality of life (QoL) measured by Lung Cancer Symptom Scale (LCSS) at every staging
The following safety assessments are considered as secondary endpoints: ? Safety profile of MGN1703 in terms of the incidence of AEs graded according to NCI CTC Version 4.03; ? Autoimmunity of MGN1703 in terms of ANA. |
? SG desde el inicio del primer ciclo del tratamiento de inducción (SG1); ? Supervivencia sin progresión (SSP) desde la fecha de aleatorización con progresión evaluada de conformidad con los criterios de evaluación de la respuesta en tumores sólidos (RECIST), versión 1.1, y los criterios de respuesta inmunitaria (CRi); ? SSP desde el inicio del primer ciclo del tratamiento de inducción (SSP1) evaluada según los criterios RECIST 1.1 y CRi; ? Mejor tasa de respuesta objetiva (TRO) con respuesta clínica evaluada según los criterios RECIST 1.1 y CRi. ? Calidad de vida (CdV) medida con la Lung Cancer Symptom Scale (LCSS) en cada estadio;
Las siguientes evaluaciones de seguridad se consideran criterios secundarios de evaluación: ? Perfil de seguridad de MGN1703 en términos de incidencia de acontecimientos adversos (AA) clasificados de acuerdo con los Criterios terminológicos comunes para acontecimientos adversos del National Cancer Institute (NCI CTC versión 4.03); ? Autoinmunidad de MGN1703 en términos de anticuerpos antinucleares (AAN) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of study |
Fin del estudio |
|
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 | 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 | 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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Tratamiento de referencia local |
Local Standard of Care |
|
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 study will be closed no later than 2 years from last patient in (LPI) |
El estudio se cerrará como mucho 2 años después de la inclusión del último paciente (IUP) |
|
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |