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

• ClinicalTrials.gov Identifier: NCT02752126
• Recruitment Status: Completed
• First Posted: April 26, 2016
• Last Update Posted: February 25, 2021
• Sponsor: Lawson Health Research Institute
• Information provided by (Responsible Party): Alexander Louie, Lawson Health Research Institute

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Non-Small Cell Lung Cancer	Radiation: Conventional radiotherapy; Radiation: Esophageal-Sparing Intensity-Modulated Radiotherapy	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Randomized Phase III Study of Palliative Radiation of Advanced Central Tumors With Intentional Avoidance of the Esophagus
• Study Start Date: June 2016
• Actual Primary Completion Date: August 1, 2020
• Actual Study Completion Date: September 1, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Esophageal Quality of Life [ Time Frame: 2 weeks after completion of radiotherapy ]
   Esophageal quality of life will be measured by the ECS of the FACT-E, measured at 2 weeks.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

Canada, Alberta

Cross Cancer Institute

Edmonton, Alberta, Canada, T6G 1Z2

Canada, Nova Scotia

Atlantic Clinical Cancer Centre

Halifax, Nova Scotia, Canada, B3H 1V7

Canada, Ontario

Grand River Regional Cancer Centre/Grand River Hospital

Kitchener, Ontario, Canada, N2G 1G3

London Regional Cancer Program

London, Ontario, Canada, N6A 4L6

Princess Margaret Hospital/ University Health Network

Toronto, Ontario, Canada, M5G 2M9

Canada, ONT

Trillium Health Partners - Credit Valley Hospital

Mississauga, ONT, Canada, L5M 2N1

Canada, Quebec

McGill University Health Centre

Montréal, Quebec, Canada, H3H 2R9

Sponsors and Collaborators

Lawson Health Research Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Alexander Louie, Radiation Oncologist, Lawson Health Research Institute
• ClinicalTrials.gov Identifier: NCT02752126
• Other Study ID Numbers: PROACTIVE
• First Posted: April 26, 2016
• Last Update Posted: February 25, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Alexander Louie, Lawson Health Research Institute:

Esophageal sparing; Conventional radiotherapy; Palliative radiation; Central lung tumors

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases