Moderately Hypofractionated Versus Conventional Chemoradiotherapy With Consolidation Immunotherapy in Patients With Unresectable, Non-Targetable Stage III Non Small Cell Lung Cancer (NSCLC) (MODERN-LUNG)
Moderately Hypofractionated Versus Conventional Chemoradiotherapy With Consolidation Immunotherapy, in Patients With Unresectable, Non-Targetable Stage III NSCLC: A Phase III Randomised Controlled Trial
This is an open-label, multi-centre, phase 3 randomised controlled trial comparing 4 weeks with 6 weeks of Chemoradiotherapy (CRT) followed by consolidation immunotherapy in patients with unresectable, non-targetable stage 3 NSCLC given with curative intent.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Tipo de estudio
Tipo de estudio
Inscripción (Estimado)
Inscripción
Fase
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
Estudio Contacto
- Nombre: Courtney Wheeler
- Número de teléfono: +61 2 40143911
- Correo electrónico: MODERN-LUNG@trog.com.au
Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Histologically proven Non-Small Cell Lung Carcinoma (NSCLC) including squamous cell carcinoma, adenocarcinoma or large cell undifferentiated carcinoma
- Stage III according to 9th edition of the AJCC/UICC TNM classification
- Unresectable
- Aged18 years or older
- Suitable for concurrent chemoradiotherapy
- Suitable for consolidation immunotherapy
- ECOG performance status 0-2
- Staging FDG-PET CT and CNS imaging within 6 weeks of randomisation
- Has provided written informed consent for participation in this trial
Exclusion Criteria:
- Targetable driver mutation
- Contraindication to curative dose radiotherapy
- Contraindication to chemotherapy
- Contraindication to immunotherapy
- Planned for induction or consolidation chemotherapy
- Previous thoracic radiotherapy with significant overlap
- Other active malignant disease interfering with completion of protocol treatment or outcomes
- Inability to attend for protocol follow-up
- Enrolled on another therapy clinical trial during treatment impacting outcomes
- Pregnant or lactating patients
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
|---|---|
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Experimental: ARM 1 - Moderately Hypofractionated Chemoradiotherapy (4 weeks)
Participants will receive moderately hypofractionated chemoradiotherapy with consolidation immunotherapy (60 Gy in 20 fractions to the primary tumour or 55 Gy in 20 fractions to involved lymph nodes (LN) 2.75 -3.0 Gy per fraction over 4 weeks). |
Participants will receive moderately hypofractionated chemoradiotherapy with consolidation immunotherapy (60 Gy in 20 fractions to the primary tumour or 55 Gy in 20 fractions to involved lymph nodes (LN) 2.75 -3.0 Gy per fraction over 4 weeks). |
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Comparador activo: ARM 2 - Standard Chemoradiotherapy (6-6.5weeks)
Participants will receive conventionally fractionated chemoradiotherapy with consolidation immunotherapy (60Gy in 30 fractions of 66Gy in 33 fractions at 2 Gy per fraction over 6-7 weeks). |
Participants will receive conventionally fractionated chemoradiotherapy with consolidation immunotherapy (60Gy in 30 fractions of 66Gy in 33 fractions at 2 Gy per fraction over 6-7 weeks). |
¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Win Ratio Based on a Hierarchical Composite Endpoint
Periodo de tiempo: From randomisation to 24 months, incorporating adverse events within 90 days of treatment commencement and healthcare contact days and quality-of-life changes within 90 days of randomisation.
|
The primary outcome is the win ratio comparing Arm 1 with Arm 2 using a hierarchical composite endpoint comprising the following components, assessed in order of priority: Progression-free survival (PFS) over 24 months, with a tie margin of 3 months. Thoracic-related adverse events assessed using CTCAE version 6.0 within 90 days of treatment commencement. Healthcare contact days within 90 days of randomisation, with a tie margin of 5 days. Change from baseline to 90 days in the EORTC QLQ-C30 global health status score, with a tie margin of 10 points. The win ratio will be used to assess whether Arm 1 is superior to Arm 2 based on the hierarchical comparison of these outcomes. |
From randomisation to 24 months, incorporating adverse events within 90 days of treatment commencement and healthcare contact days and quality-of-life changes within 90 days of randomisation.
|
Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Progression free survival (PFS)
Periodo de tiempo: From randomisation to disease progression or death from any cause, assessed up to 24 months.
|
Progression-free survival is defined as the time from randomisation to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be compared between Arm 1 and Arm 2. |
From randomisation to disease progression or death from any cause, assessed up to 24 months.
|
|
Proportion of Participants Experiencing Grade ≥3 Thoracic-Related Adverse Events
Periodo de tiempo: From treatment commencement to 90 days after treatment commencement.
|
The proportion of participants experiencing at least one Grade 3 or higher thoracic-related adverse event, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0. The proportion will be compared between Arm 1 and Arm 2. |
From treatment commencement to 90 days after treatment commencement.
|
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Number of Healthcare Contact Days
Periodo de tiempo: From randomisation to 90 days after randomisation.
|
The number of days with any hospital-based healthcare contact, including scheduled treatment attendances, inpatient hospitalisation days or emergency department presentations. Multiple healthcare contacts occurring on the same day will be counted as one healthcare contact day. The number of healthcare contact days will be compared between Arm 1 and Arm 2. |
From randomisation to 90 days after randomisation.
|
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Change From Baseline in Quality of Life Scores at 90 Days
Periodo de tiempo: Baseline to 90 days after randomisation.
|
Change from baseline to 90 days in global health status/quality of life, assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The global health status/quality of life scale is scored from 0 to 100, with higher scores indicating better global health status and quality of life. |
Baseline to 90 days after randomisation.
|
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Overall Survival (OS)
Periodo de tiempo: From randomisation to death from any cause, assessed up to 24 months
|
Overall survival is defined as the time from randomisation to death from any cause. Overall survival will be compared between Arm 1 and Arm 2. |
From randomisation to death from any cause, assessed up to 24 months
|
|
Patterns of First Disease Recurrence or Progression
Periodo de tiempo: From randomisation to first documented disease recurrence or progression, assessed up to 24 months.
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The pattern of first disease recurrence or progression will be classified as local progression (in-field recurrence involving the treated primary tumour or nodal disease), regional progression (out-of-field recurrence involving non-treated intrathoracic regional lymph nodes), distant recurrence (recurrence at sites not classified as local or regional, including the non-treated lung), or a combination of these categories. Patterns of first recurrence or progression will be compared between Arm 1 and Arm 2. |
From randomisation to first documented disease recurrence or progression, assessed up to 24 months.
|
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Incremental Cost per Quality-Adjusted Life Year (QALY) Gained
Periodo de tiempo: From randomisation to 24 months
|
Cost-effectiveness will be compared between Arm 1 and Arm 2 using the incremental cost-effectiveness ratio (ICER), calculated as the difference in healthcare costs between treatment arms divided by the difference in quality-adjusted life years (QALYs) gained. |
From randomisation to 24 months
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Otras medidas de resultado
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Longitudinal Changes in Circulating Immune Biomarkers and Cell-Free/Circulating Tumour DNA (cfDNA/ctDNA)
Periodo de tiempo: Baseline (prior to radiotherapy), Week 2 of radiotherapy, final week of radiotherapy (Week 4 or Week 6-7, depending on treatment arm), 4-6 weeks after radiotherapy, and at disease recurrence or progression, assessed up to 24 months.
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Longitudinal changes in circulating immune biomarkers, cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) will be assessed and compared between Arm 1 and Arm 2. Associations between biomarker measures and progression-free survival (PFS), overall survival (OS) and treatment-related adverse events will also be evaluated. |
Baseline (prior to radiotherapy), Week 2 of radiotherapy, final week of radiotherapy (Week 4 or Week 6-7, depending on treatment arm), 4-6 weeks after radiotherapy, and at disease recurrence or progression, assessed up to 24 months.
|
Colaboradores e Investigadores
Patrocinador
Patrocinador
Colaboradores
Colaboradores
Investigadores
Investigadores
- Silla de estudio: Joanna J Ludbrook, Calvary Mater Newcastle
- Silla de estudio: Shalini Vinod, Liverpool Hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Inicio del estudio
Finalización primaria (Estimado)
Finalización primaria
Finalización del estudio (Estimado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- TROG 24.01 MODERN-LUNG
- TOGA 25/003 (Otro identificador: Thoracic Oncology Group of Australasia)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
De-identified individual participant data collected during the trial may be made available to researchers following publication of the final analysis, with no specified end date. Access will be granted to researchers submitting a methodologically sound proposal detailing the research purpose, data requirements and analysis plan. Requests will be subject to approval by the TROG Scientific Committee, in consultation with the Trial Management Committee and, where required, the TROG Secondary Data Analysis Committee. Evidence of ethics approval and an executed data sharing agreement will be required before data transfer.
Marco de tiempo para compartir IPD
De-identified individual participant data will be available following publication of the final trial analysis, with no specified end date.
Criterios de acceso compartido de IPD
Access may be granted to researchers who submit a methodologically sound proposal detailing the research purpose, specific data requested, data formats, access methods and analysis plan. Requests are subject to approval by the TROG Scientific Committee, in consultation with the MODERN-LUNG Trial Management Committee and, where required, the TROG Secondary Data Analysis Committee. Evidence of ethics approval and an executed data sharing agreement will be required prior to data transfer. Requests can be submitted via https://www.trog.com.au/New-proposals.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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