A Randomized Phase III Study of Palliative Radiation of Advanced Central Tumors With Intentional Avoidance of the Esophagus (PROACTIVE)

A randomized phase II study of palliative radiation of advanced central lung tumors with intentional avoidance of the esophagus. Patients will be randomized between standard of care palliative thoracic radiation and esophageal-sparing intensity-modulated radiation therapy (ES-IMRT) in a 1:1 ratio. Radiotherapy will be administered as soon as possible following randomization and subjects will be followed for 1 year after completion of their radiation therapy. The primary endpoint is esophageal quality of life as measured by the Esophageal Cancer Subscore (ECS) of the Functional Assessment of Cancer Therapy-Esophagus (FACT-E).

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Radiation: Conventional radiotherapy; Radiation: Esophageal-Sparing Intensity-Modulated Radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Atlantic Clinical Cancer Centre
  • ONT
    • Mississauga, ONT, Canada, L5M 2N1
      • Trillium Health Partners - Credit Valley Hospital
  • Ontario
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Regional Cancer Centre/Grand River Hospital
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital/ University Health Network
  • Quebec
    • Montréal, Quebec, Canada, H3H 2R9
      • McGill University Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Joint Committee on Cancer (AJCC) 7th edition stage IV NSCLC or stage III not eligible for curative intent treatment
• Intended to receive palliative radiotherapy to the thorax, to a dose of 30Gy in 10 fractions or 20Gy in 5 fractions. In either treatment arm at least 5cm of the esophagus should be in the intended treatment field.
• Willingness and ability to provide informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status 0-3
• Age 18 years or older
• Prior or planned systemic therapy (chemotherapy, immunotherapy, targeted agents) is permissible at the discretion of the treating medical oncologist, provided that no systemic treatment is given within 2 weeks prior to RT, concurrent with RT or within a 2-week period post RT.
• Concurrent palliative RT to other metastatic sites is permissible
• Life expectancy > 3 months

Exclusion Criteria:

• Prior thoracic RT
• Serious medical comorbidities precluding RT
• Pregnant or lactating women
• Inability to attend the full course of RT or planned follow-up visits
• Planned concurrent palliative RT to the stomach and/or liver
• Congenital abnormalities of the esophagus or severe disorders of the esophagus (e.g. achalasia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Palliative Radiation; Patients in the standard arm will receive a conventional radiotherapy dose will be either 30 gray (Gy) in 10 fraction or 20Gy in 5 fractions. Patients will be stratified by intended dose prior to randomization. Radiation for patients in the standard arm should adhere to the principles of palliative radiation, with goals of alleviating symptoms or preventing potential complications.	Radiation: Conventional radiotherapy; Patients will receive standard palliative radiation in dose of 30Gy in 10 fractions, or 20Gy in 5 fractions.
Experimental: Esophageal Sparing IMRT; Patients on the experimental arm will receive esophageal-sparing intensity-modulated radiotherapy, with the same dose(s) as in the standard arm.	Radiation: Esophageal-Sparing Intensity-Modulated Radiotherapy; Patients will receive esophageal-sparing intensity-modulated radiotherapy, of 30Gy in 10 fractions or 20Gy in 5 fractions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Esophageal Quality of Life	Esophageal quality of life will be measured by the ECS of the FACT-E, measured at 2 weeks.	2 weeks after completion of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Survival	6 months after completion of radiotherapy
Toxicity Rate Differences	Differences in rates of grade 2 or higher toxicity between groups will be tested using the Fisher's Exact test.	6 months after completion of radiotherapy
Progression-Free Survival	Differences in local/regional progression-free survival will be tested using the stratified log-rank test	6 months after completion of radiotherapy
Further Systemic Therapy	Differences in number of cycles of further systemic therapy will be tested using the student's t-test	6 months after completion of radiotherapy
Cost-Effectiveness/Utility Analysis	European Quality of Life-5 Dimensions (EQ-5D) measurements will be converted into utilities to inform cost-effectiveness/utility analysis.	6 months after completion of radiotherapy
Dosimetry Comparison - Gross Tumor Volume (GTV)	Dosimetric comparison of GTV will be compared using the student's t-test.	6 months after completion of radiotherapy
Dosimetry Comparison - Planning Target Volume (PTV)	Dosimetric comparison of PTV will be compared using the student's t-test.	6 months after completion of radiotherapy
Dosimetry Comparison - Pulmonary Metrics	Dosimetric comparison of standard pulmonary metrics will be compared using the student's t-test.	6 months after completion of radiotherapy
Dosimetry Comparison - Esophageal Metrics	Dosimetric comparison of standard esophageal metrics will be compared using the student's t-test.	6 months after completion of radiotherapy

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute

Publications and helpful links

General Publications

• Louie AV, Granton PV, Fairchild A, Bezjak A, Gopaul D, Mulroy L, Brade A, Warner A, Debenham B, Bowes D, Kuk J, Sun A, Hoover D, Rodrigues GB, Palma DA. Palliative Radiation for Advanced Central Lung Tumors With Intentional Avoidance of the Esophagus (PROACTIVE): A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2022 Apr 1;8(4):1-7. doi: 10.1001/jamaoncol.2021.7664.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: April 22, 2016
• First Submitted That Met QC Criteria: April 22, 2016
• First Posted (Estimate): April 26, 2016

Study Record Updates

• Last Update Posted (Actual): February 25, 2021
• Last Update Submitted That Met QC Criteria: February 24, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Esophageal sparing; Conventional radiotherapy; Palliative radiation; Central lung tumors
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: PROACTIVE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No