Image-Guided Functional Lung Avoidance Thoracic Radiotherapy for Lung Cancer: A Single-Blind Randomized Trial

A Single-Blind Randomized Trial of Image-Guided Functional Lung Avoidance Thoracic Radiotherapy for Locally Advanced Non-Small Cell and Small Cell Lung Cancer

Thoracic radiotherapy (TRT) is a standard curative treatment for locally advanced, unresectable non-small cell lung cancer (NSCLC) and limited stage small cell lung cancer (SCLC). TRT has been recognized to cause moderate to severe lung injury in a substantial portion of patients. Conventional standard curative TRT planning techniques minimize the radiation dose to the anatomical lungs, without adaption of regional pulmonary function variations. The principal investigator hypothesized that preferential avoidance of functional lung during curative TRT may decrease the risk of pulmonary toxicity. Functional lung regions are identified using four- dimensional computed tomography for ventilation imaging. This randomized, single-blind trial will comprehensively assess the impact of functional lung avoidance on pulmonary toxicity, quality of life, and clinical outcome in patients receiving curative TRT for locally advanced NSCLC and SCLC.

Study Overview

• Status: Recruiting
• Conditions: Stage III Non-small Cell Lung Cancer; Small Cell Lung Cancer, Limited Stage
• Intervention / Treatment: Radiation: Functional Lung Avoidance Thoracic Radiotherapy; Radiation: Standard Thoracic Radiotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Feng-Ming Hsu, MD; Phone Number: 67061 +886-2-23123456; Email: hsufengming@ntuh.gov.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Feng-Ming Hsu, MD; Phone Number: 67061 +886-2-23123456; Email: hsufengming@ntuh.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Patients with a histologic diagnosis of non-small cell carcinoma or small cell carcinoma of lung
2. Locally advanced stage III A or III B lung carcinoma according to American Joint Committee on Cancer (AJCC) 7th edition or highly selected patients with oligo-metastatic disease amendable for thoracic radiotherapy with curative intent
3. Not undergoing radical surgical resection
4. Patients do not have prior radiotherapy to the thorax
5. Age ≥ 20 years
6. Karnofsky performance status (KPS) ≥ 60%.
7. Women of childbearing potential and male participants must practice adequate contraception
8. Patients must be able to comply with the study protocol and follow-up schedules and provide study-specific informed consent

Exclusion criteria:

1. Prior radiotherapy to thorax
2. Unable to receive assigned radiation dose due to normal lung constraint
3. Inability to attend full course of radiotherapy or follow-up visits
4. Presence of metastatic disease. Patients who present with oligo-metastatic disease where all metastases have been ablated (with surgery or radiotherapy) or in complete remission after systemic therapy are candidates if they are receiving radiotherapy to the thoracic disease with curative intent

5. Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:

   • Uncontrolled active infection requiring intravenous antibiotics at the time of registration
   • Transmural myocardial infarction ≤ 6 months prior to registration.
   • Unstable angina or congestive heart failure requiring hospitalization ≤ 6 months prior to registration.
   • Life-threatening uncontrolled clinically significant cardiac arrhythmias.
   • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
   • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
   • Uncontrolled psychiatric disorder.
6. Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic.
7. Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Functional Lung Avoidance-TRT; Functional Lung Avoidance Thoracic Radiotherapy The avoidance thoracic radiotherapy treatment plan will be designed to optimize such that radiation dose to functional lung identified by four-dimensional (4D) CT ventilation imaging is as low as reasonably achievable	Radiation: Functional Lung Avoidance Thoracic Radiotherapy; Chemoradiation for non-small cell lung cancer: 60 Gy in 30 once-daily fractions (Dose reduction to 54 Gy in 30 once-daily fractions is allowed); Radiation alone for non-small cell lung cancer: 60 Gy in 25 once-daily fractions (Dose reduction to 55 Gy in 25 once-daily fractions is allowed); Chemoradiation for small-cell lung cancer: 45 Gy in 30 twice-daily fractions
Active Comparator: Standard-TRT; Standard Thoracic Radiotherapy The standard thoracic radiotherapy treatment plan will be designed without reference to the functional lung 4D CT ventilation imaging	Radiation: Standard Thoracic Radiotherapy; Chemoradiation for non-small cell lung cancer: 60 Gy in 30 once-daily fractions (Dose reduction to 54 Gy in 30 once-daily fractions is allowed); Radiation alone for non-small cell lung cancer: 60 Gy in 25 once-daily fractions (Dose reduction to 55 Gy in 25 once-daily fractions is allowed); Chemoradiation for small-cell lung cancer: 45 Gy in 30 twice-daily fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The pulmonary quality of life at 3 months post-radiotherapy	Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS)	Change from Baseline Functional Assessment of Cancer Therapy-Lung Cancer Subscale at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Number of participant alive	From date of enrollment until the date of death from any cause, assessed up to 60 months
Changes of pulmonary function test post-radiotherapy	Screening spirometry, diffusion capacity of lung for carbon monoxide	At baseline, 3, 6, 12 months, and annually until year 5 post-radiotherapy
Patient reported outcome (Quality of Life questionnaire by Functional Assessment of Cancer Therapy)	Functional Assessment of Cancer Therapy-Lung	At baseline, 1, 2, 3, 4, 6, 9 12 months post-radiotherapy
Patient reported outcome (Quality of Life questionnaire by EORTC Core)	EORTC Quality of Life-Core 30 questionnaire module	At baseline, 1, 2, 3, 4, 6, 9 12 months post-radiotherapy
Patient reported outcome (Quality of Life questionnaire by EORTC Lung cancer)	EORTC Quality of Life questionnaire -Lung cancer 13	At baseline, 1, 2, 3, 4, 6, 9 12 months post-radiotherapy
Acute toxicity	Common Toxicity Criteria for Adverse Events version 4	From date of radiotherapy until 90 days after radiotherapy starts
Late toxicity	Common Toxicity Criteria for Adverse Events version 4	90 days after radiotherapy starts until the date of death from any cause, up to 60 months
Progression free survival	Number of participant without disease progression	From date of enrollment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum biomarkers in association with radiation pneumonitis	Tumor necrosis factor-alpha, Transforming growth factor-beta concentration measured by ELISA	At baseline, 1, 2, 3, 4, 6 months post-radiotherapy

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: June 27, 2016
• First Submitted That Met QC Criteria: March 7, 2017
• First Posted (Actual): March 13, 2017

Study Record Updates

• Last Update Posted (Actual): March 11, 2019
• Last Update Submitted That Met QC Criteria: March 7, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Lung Cancer; Quality of Life; Radiotherapy; Biomarkers; Radiation Lung Injury
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: 201604007RINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED