| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| advanced dedifferentiated liposarcoma |
| Liposarcoma desdiferenciado avanzado |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10073135 |
| E.1.2 | Term | Dedifferentiated liposarcoma |
| 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 trial will assess the efficacy and safety of BI 907828 compared to doxorubicin as first
line systemic therapy for advanced or metastatic DDLPS. |
| El ensayo evaluará la eficacia y la seguridad de BI 907828 en comparación con la doxorrubicina como tratamiento sistémico de primera línea para el liposarcoma desdiferenciado (LPSDD) avanzado o metastásico. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the Phase II part of the trial are to select an optimal dose of BI 907828 and to evaluate prior to the Phase III part whether the expected benefits of BI 907828 as first line systemic therapy for advanced or metastatic DDLPS outweigh any risks. The secondary objectives of the Phase III part of the trial are to evaluate whether BI 907828 as first line systemic therapy for advanced or metastatic DDLPS improves the objective response rate, duration of responses, overall survival, disease control rate, tolerability and delays worsening of quality of life, compared to doxorubicin.
Safety of BI 907828 will be investigated in both parts of the trial. |
Los objetivos secundarios de la fase II del ensayo son seleccionar una dosis óptima de BI 907828 y evaluar antes de la fase III si los beneficios esperados de BI 907828 como tratamiento sistémico de primera línea para LPSDD avanzado o metastásico superan cualquier riesgo. Los objetivos secundarios de la fase III del ensayo son evaluar si BI 907828 como tratamiento sistémico de primera línea para la LPSDD avanzado o metastásico mejora la tasa de respuesta objetiva, la duración de las respuestas, la supervivencia global, la tasa de control de la enfermedad, la tolerabilidad y si retrasa el empeoramiento de la calidad de vida, en comparación con la doxorrubicina.
La seguridad de BI 907828 será investigada en ambas partes del ensayo. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Provision of signed and dated, written informed consent form ICF in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
2. Male or female patients ≥18 years old at the time of signature of the ICF. Women of childbearing potential and men able to father a child must be ready and able to use 2 medically acceptable methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at screening, during trial participation, and until 6 months and 12 days after last dose for women and 102 days after last dose for men.
3. Histologically proven locally advanced or metastatic, unresectable (surgery morbidity
would outweigh potential benefits), progressive or recurrent DDLPS. Locally performed histopathological diagnosis will be accepted for entry into this trial but will be confirmed by independent pathological review while the patients receive treatment in this trial.
4. Written pathology report indicating the diagnosis of DDLPS with positive MDM2 immunohistochemistry or MDM2 amplification as demonstrated by fluorescence in situ hybridization or NGS must be available.
5. Formalin fixed paraffin embedded tumor blocks or slides must be available for retrospective histopathological central review.
6. Presence of at least one measurable target lesion according to RECIST version 1.1. In patients who only have one target lesion, the baseline imaging must be performed at least 2 weeks after any biopsy of the target lesion.
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
8. Patient must be willing to donate blood samples for the pharmacokinetics, pharmacodynamics, and tumor mutation analysis.
9. Patient willing to undergo a mandatory tumor biopsy at the time point specified in the flowchart unless exempt.
10. Adequate organ function |
1. Provisión del formulario escrito de consentimiento informado (CI), firmado y fechado conforme con la ICH-GCP y la legislación local antes de cualquier procedimiento, muestreo o análisis específicos de un ensayo.
2. Pacientes hombres o mujeres con edad ≥18 años en el momento de la firma del CI. Las mujeres en edad fértil y los hombres capaces de engendrar un hijo deben estar preparados y ser capaces de utilizar 2 métodos anticonceptivos médicamente aceptables por la ICH M3 (R2) que den lugar a una tasa de fracaso baja de menos del 1% anual cuando se utilicen de forma coherente y correcta empezando en el cribado, durante la participación en el ensayo, y hasta 6 meses y 12 días después de la última dosis para las mujeres y 102 días después de la última dosis para los hombres.
3. LPSDD localmente avanzado o metastásico histológicamente confirmado, irresecable (la morbilidad de la cirugía superaría los beneficios potenciales), progresivo o recurrente. El diagnóstico histopatológico realizado localmente será aceptado para participar en este ensayo pero será confirmado por una revisión patológica independiente mientras los pacientes reciben tratamiento en este ensayo.
4. Deberá disponerse de un informe patológico escrito que indique el diagnóstico de LPSDD con inmunohistoquímica MDM2 positiva o amplificación MDM2 demostrado mediante hibridación in situ por fluorescencia o NGS.
5. Deben estar disponibles los bloques o láminas tumorales fijados en formol e incluidos en parafina o muestras en portaobjetos para una revisión central histopatológica retrospectiva.
6. Presencia de al menos una lesión diana medible según RECIST versión 1.1. En pacientes que solo tengan una lesión diana, la toma de imágenes de inicio debe realizarse al menos 2 semanas después de cualquier biopsia de la lesión diana.
7. Puntuación de 0 o 1 del estado funcional según el Eastern Cooperative Oncology Group (ECOG).
8. El paciente debe estar dispuesto a donar muestras de sangre para el análisis farmacocinético, farmacodinámico y de mutación tumoral.
9. Paciente dispuesto a someterse a una biopsia tumoral obligatoria en el momento especificado en el diagrama de flujo a menos que esté exento.
10. Función orgánica adecuada |
|
| E.4 | Principal exclusion criteria |
1. Known mutation in the TP53 gene (screening for TP53 status is not required).
2. Major surgery (major according to the investigator’s assessment) performed within
4 weeks prior to randomization or planned within 6 months after screening.
3. Prior systemic therapy for liposarcoma in any setting (including adjuvant, neoadjuvant, maintenance, palliative).
4. Previous or concomitant malignancies other than DDLPS or WDLPS, treated within the previous 5 years, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ, and prostate cancer.
5. Previous treatment with anthracyclines in any setting (systemic treatment with other anticancer agents is allowed if completed at least 5 years prior to study entry with the exception of hormone therapy).
6. Patients who must or intend to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
7. Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s) or receiving other investigational treatment(s).
8. Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator’s opinion, makes the patient an unreliable trial participant).
Further criteria apply. |
1. Mutación conocida en el gen TP53 (no se requiere la detección del estado de TP53).
2. Cirugía mayor (mayor según la evaluación del investigador) realizada en las 4 semanas anteriores a la aleatorización o programada en los 6 meses siguientes a la selección.
3. Terapia sistémica previa para el liposarcoma en cualquier entorno (incluyendo adyuvante, neoadyuvante, de mantenimiento y paliativo).
4. Neoplasias malignas anteriores o concomitantes distintas de LPSDD o LPSBD, tratadas en los 5 años anteriores, excepto cánceres de piel no melanocíticos tratados eficazmente, carcinoma in situ del cuello uterino, carcinoma ductal in situ y cáncer de próstata.
5. Tratamiento previo con antraciclinas en cualquier contexto (se permite el tratamiento sistémico con otros agentes antineoplásicos si se completó al menos 5 años antes del ingreso en el estudio, con la excepción de la hormonoterapia).
6. Pacientes que deben o deseen continuar tomando medicamentos restringidos o algún fármaco que se considere que pueda interferir en la realización segura del ensayo.
7. Actualmente inscrito en otro dispositivo de investigación o ensayo con medicamentos, o hace menos de 30 días desde que finalizó otro dispositivo de investigación u ensayo(s) con medicamentos o bien recibe otro(s) tratamiento(s) de investigación.
8. Pacientes que no se espera que cumplan los requisitos del protocolo o que completen el ensayo según lo programado (por ejemplo, alcoholismo crónico o drogadicción o cualquier otra afección que, en opinión del investigador, convierta al paciente en un participante poco fiable para el ensayo).
Se aplican más criterios. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression-free survival (PFS) |
| Supervivencia sin progresión (SSP) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 1) 12 and 23 months |
| 1) 12 y 23 meses |
|
| E.5.2 | Secondary end point(s) |
1) Objective response (OR)
2) Duration of objective response (DOR)
3) Overall survival (OS)
4) Disease control (DC)
5) Health-Related Quality of Life (HRQoL) |
1) Respuesta objetiva (RO)
2) Duración de la respuesta objetiva (DRO)
3) Supervivencia global (SG)
4) Control de enfermedades (CE)
5) Calidad de vida relacionada con la salud (CdVRS) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) 12 and 23 months
2) 12 and 23 months
3) 12 and 23 months
4) 12 and 23 months
5) 12 and 23 months |
1) 12 y 23 meses
2) 12 y 23 meses
3) 12 y 23 meses
4) 12 y 23 meses
5) 12 y 23 meses |
|
| 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 | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| 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) | 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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Pacientes con FD objetiva pueden, si son elegibles, cambiar a BI 907828 |
| doxorubicin patients with objective PD can, if eligible, switch to BI 907828 |
|
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 44 |
| 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 |
| China |
| Czechia |
| Denmark |
| Finland |
| France |
| Germany |
| Greece |
| Hong Kong |
| Ireland |
| Italy |
| Japan |
| Korea, Republic of |
| Netherlands |
| Norway |
| Philippines |
| Portugal |
| Russian Federation |
| Spain |
| Sweden |
| Taiwan |
| Turkey |
| United Kingdom |
| United States |
|
| 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
|
| LVLS |
| Última visita del último paciente |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| 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 | 19 |
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