Viewing Study NCT04577638



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Last Modification Date: 2024-10-26 @ 1:46 PM
Study NCT ID: NCT04577638
Status: COMPLETED
Last Update Posted: 2024-02-07
First Post: 2020-09-30

Brief Title: Accelerated Radio-Immunotherapy for Lung Cancer
Sponsor: Center Eugene Marquis
Organization: Center Eugene Marquis

Study Overview

Official Title: A Phase II Trial Evaluating Conformational Intensity Modulated Radiotherapy With Concomitant Nivolumab Followed by Nivolumab for Patients With Locally Advanced Non-small Cell Lung Cancer
Status: COMPLETED
Status Verified Date: 2024-02
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: AIRING
Brief Summary: Radiotherapy RT at a total dose of 60-66 Gy over 6 weeks combined with platinum-based chemotherapy is the standard of care for stage III Non-Small Cell Lung Cancers NSCLC patients with unresectable or inoperable disease However the long-term outcomes are poor with a 5-year overall survival OS rate of 15-35 for stage IIIA and 5-10 for stage IIIB patients The recent association of immunotherapy has been proven to improve Progression Free Survival PFS and OS for these patients and durvalumab consolidation following chemoradiotherapy CT-RT is now the new standard of care

Compared to older technics 2DimensionsD and 3D-RT intensity-modulated radiotherapy IMRT allows for improved organs-at-risk sparing owing to the high dose conformation to the target volume thus reducing toxicity rates

In regard to the recent results of adjuvant immunotherapy the benefits of concomitant chemotherapy with radiotherapy could be re-evaluated With the changing landscape in the standard treatment of Local Advanced NSCLC LA-NSCLC the reduction in treatment-induced toxicity while maintaining optimal tumor control has become a priority thereby warranting access to adjuvant immunotherapy for these patients Due to the toxicity of the chemoradiotherapy a large subset of patients may be unfit for the adjuvant immunotherapy The use of immunotherapy concomitant to radiotherapy without chemotherapy may be the next step Nevertheless as immune cells are highly sensitive to conventional RT doses the paradigm of the standard irradiation volumes should be reconsidered In this context the introduction of IMRT to spare lymphatic tissues and bone marrow deserves evaluation in prospective trials

A strong body of evidence supports the combination of RT with immunotherapy such as a Programmed cells Death-1 PD1 inhibitor Radiation alone can modify the immune response in several ways to allow for synergistic effects when combined with immunotherapy

The reduction in treatment-induced toxicity while maintaining optimal tumor control has become a priority thereby warranting access to adjuvant immunotherapy for these patients In this context the introduction of IMRT to spare lymphatic tissues and bone marrow deserves evaluation in prospective trials

The timing of administration of immunotherapy seems to be a major point Previous data in mice showed that an improved survival benefit with concurrent anti-PD-Ligand1 PD-L1 and RT versus sequential administration Moreover for sequential schedule an improved survival outcome was found for patients receiving first dose of durvalumab within 14 days of last radiotherapy fraction compared to 14 days or greater

Furthermore immunotherapy combined with radiotherapy appears to be safe without increase of the toxicity

In summary there is a strong rationale for testing this new paradigm of accelerated IMRT combined with concurrent and maintenance nivolumab for locally advanced non-small lung cancer due to

The unmet medical need for new Standard Of Care SOC better tolerated and as or more effective treatment than CT-RT
The need to decrease radiation-induced toxicity
The limit of CT-RT followed by durvalumab consolidation leading to a high rate of recurrence within the 18 months 18-month PFS rate of 442
The strong rationale to combine RT and PD-1 inhibition

It is hypothesized this innovative concept to be safe in the context of this study for the following reasons

The use of moderate accelerated intensity-modulated radiotherapy H-IMRT allows decreasing both the Overall Treatment Time OTT and the dose to the organs at risk
The decrease of the OTT 24 fractions instead of 33 fractions combined with a decrease of the toxicity should represent a potential clinical benefit
Detailed Description: None

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: False
Is a FDA Regulated Device?: False
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None