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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Estimé)
Phase
- N'est pas applicable
Contacts et emplacements
Coordonnées de l'étude
- Nom: Courtney Wheeler
- Numéro de téléphone: +61 2 40143911
- E-mail: MODERN-LUNG@trog.com.au
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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 d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: 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). |
|
Comparateur actif: 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). |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Win Ratio Based on a Hierarchical Composite Endpoint
Délai: 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.
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Progression free survival (PFS)
Délai: 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
Délai: 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.
|
|
Number of Healthcare Contact Days
Délai: 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.
|
|
Change From Baseline in Quality of Life Scores at 90 Days
Délai: 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.
|
|
Overall Survival (OS)
Délai: 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
Délai: From randomisation to first documented disease recurrence or progression, assessed up to 24 months.
|
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.
|
|
Incremental Cost per Quality-Adjusted Life Year (QALY) Gained
Délai: 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
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Longitudinal Changes in Circulating Immune Biomarkers and Cell-Free/Circulating Tumour DNA (cfDNA/ctDNA)
Délai: 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.
|
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.
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chaise d'étude: Joanna J Ludbrook, Calvary Mater Newcastle
- Chaise d'étude: Shalini Vinod, Liverpool Hospital
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- TROG 24.01 MODERN-LUNG
- TOGA 25/003 (Autre identifiant: Thoracic Oncology Group of Australasia)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime 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.
Délai de partage IPD
De-identified individual participant data will be available following publication of the final trial analysis, with no specified end date.
Critères d'accès au partage 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.
Informations sur les médicaments et les dispositifs, documents d'étude
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