Functional Lung Avoidance for Individualized Radiotherapy (FLAIR): A Randomized, Double-Blind Clinical Trial

Phase 2

Terminated

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: Concurrent platinum-based chemotherapy; Radiation: Standard Radiotherapy, 60 Gy in 30 fractions.; Radiation: Functional Lung Avoidance Radiotherapy, 60 Gy in 30 fractions

• Registration Number: NCT02002052
• Lead Sponsor: Lawson Health Research Institute

Brief Summary

Concurrent chemoradiotherapy is the standard treatment for locally advanced, unresectable non-small cell lung cancer, but carries a risk of radiation pneumonitis of approximately 30%, and is associated with a decline in pulmonary quality of life.

Standard radiation planning aims to optimize dose to the anatomic lung volume, without consideration of the differences in regional lung function. Functional lung avoidance radiotherapy aims to reduce radiotherapy dose to regions of functioning lung, instead depositing dose in areas of lung that are not well-ventilated. Functional lung regions are determined using noble-gas MRI and co-registered to the radiotherapy planning CT scans. Functional lung avoidance radiotherapy has been demonstrated to be feasible, and this trial aims to compare outcomes between standard radiotherapy (with concurrent chemotherapy) vs. functional lung avoidance radiotherapy (with concurrent chemotherapy).

Detailed Description

All consenting patients will undergo hyperpolarized noble gas MRI using 3-He for definition of functional lung volumes. Two radiotherapy treatment plans will be generated prior to randomization: one standard plan using anatomical lung avoidance, and one functional lung avoidance plan. After approval of both plans, patients will be randomized, and both patients and physicians will be blinded to treatment allocation.

Study Timeline

• Study First Submitted: 2013-11-29
• Study First Submitted QC: 2013-11-29
• Study First Posted: 2013-12-05
• Study Start: 2014-05
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Status Verified: 2018-01
• Last Update Submitted: 2019-09-23
• Last Update Posted: 2019-09-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• Age 18 or older
• Willing to provide informed consent
• ECOG performance status 0-2
• Histologically confirmed non-small cell lung carcinoma
• Locally advanced Stage IIIA or IIIB lung carcinoma according to AJCC 7th edition
• History of at least 10-pack-years of smoking
• Not undergoing surgical resection
• Assessment by medical oncologist and radiation oncologist, with adequate bone marrow, hepatic and renal function for administration of platinum-based chemotherapy

Exclusion Criteria

• Contraindications to MRI
• Serious medical comorbidities (such as unstable angina, sepsis) or other contraindications to radiotherapy or chemotherapy
• Prior history of lung cancer within 5 years
• Prior thoracic radiation at any time
• Metastatic disease. Patients who present with oligometastatic disease where all metastases have been ablated (with surgery or radiotherapy) are candidates if they are receiving chemoradiotherapy to the thoracic disease with curative intent.
• Inability to attend full course of radiotherapy or follow-up visits
• Pregnant or lactating women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Arm	Concurrent platinum-based chemotherapy	Standard platinum-based chemoradiotherapy, total radiation dose 60 Gy in 30 fractions
Standard Arm	Standard Radiotherapy, 60 Gy in 30 fractions.	Standard platinum-based chemoradiotherapy, total radiation dose 60 Gy in 30 fractions
Experimental Arm	Concurrent platinum-based chemotherapy	Functional-lung avoidance radiotherapy, total dose 60 Gy in 30 fractions, with concurrent platinum-based chemotherapy
Experimental Arm	Functional Lung Avoidance Radiotherapy, 60 Gy in 30 fractions	Functional-lung avoidance radiotherapy, total dose 60 Gy in 30 fractions, with concurrent platinum-based chemotherapy

Primary Outcome Measures

Name	Time	Method
Pulmonary quality of life 3-months post-treatment.	3-months post-treatment	Measured using the Functional-Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS)

Secondary Outcome Measures

Name	Time	Method
Quality of life at other time points	up to 1 year	Measured using the FACT-LCS, FACT-TOI, and FACT-L
Toxicity	up to 1 yr	CTC-AE version 4
Overall Survival	5-years	Defined as time from randomization to death from any cause
Progression Free Survival	Up to 5 years	Time from randomization to disease progression at any site or death
Quality-adjusted survival	Up to 5 years	Based on utilities from EQ-5D

Trial Locations

Locations (1)

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada