Assessing the Efficacy and Safety of Selective Metabolically Adaptive Radiation Dose Escalation in Locally Advanced Non-Small Cell Lung Cancer Receiving Definitive Chemoradiotherapy (PET-BOOST)

A Randomized Phase II Trial to Assess the Efficacy and Safety of Selective Metabolically Adaptive Radiation Dose Escalation in Locally Advanced Non-Small Cell Lung Cancer Receiving Definitive Chemoradiotherapy

A randomized phase II trial to assess the efficacy and safety of selective metabolically adaptive radiation dose escalation in locally advanced non-small cell lung cancer receiving definitive chemoradiotherapy. Eligible and consenting patients will be randomized to receive conventional chemoradiotherapy or chemoradiotherapy with a radiation (RT) integrated boost. All patients will receive a fludeoxyglucose-positron emission tomography (FDG-PET) scan within two weeks prior to starting treatment. The primary outcome is to determine if dose escalation to metabolically active tumor subvolumes will reduce local-regional failure rate at 2 years.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Radiation: Chemoradiotherapy; Radiation: Chemoradiotherapy with Integrated Boost Dose

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alex Sun, MD, FRCPC; Phone Number: 416 946 4545; Email: alex.sun@rmp.uhn.on.ca
• Study Contact Backup: Name: David Palma, MD, FRCPC; Phone Number: 519-685-8500; Email: david.palma@lhsc.on.ca

Study Locations

• Canada
  • Quebec, Canada, G2L 2Z3
    • CHU de Quebec - L'Hotel-Dieu de Quebec
  • Ont
    • Kingston, Ont, Canada, K7L 2V7
      • Kingston General Hospital
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Newmarket,, Ontario, Canada, L3Y 2P9
      • Stronach Regional Cancer Centre at Southlake Regional Health Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal,, Quebec, Canada, H4A 3J1
      • McGill University Health Centre, Glen site Cedars Cancer Center
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CHUS - Hôpital Fleurimont

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients who are at least 18 years old and are able to consent
• Patients who will undergo Chemo-RT as primarily modality of treatment
• Patients with a primary tumor or node measuring at least 10mm on CT scan
• Patients with a PET avid tumor having Standardized Uptake Values (SUV) > 4
• Patients with Eastern Cooperative Oncology Group (ECOG) status 0-2 within 4 weeks of randomization

Exclusion Criteria:

• Trimodality patients who have surgery as part of curative treatment
• Previous radiotherapy to intended treatment volumes
• Active invasive malignancy other than lung cancer
• Active pregnancy
• Poor respiratory function (Forced Expiratory Volume < 1.0 or Diffusing Capacity < 50% age-adjusted normal)
• ECOG status > 2
• Pre-treatment complete blood count/differential showing inadequate bone marrow reserve (absolute neutrophil count < 1800 cells/mm3 or platelets < 100 000 cells/mm3 or hemoglobin < 90g/L), measured within 4 weeks of registration
• AST, ALT or total bilirubin > 2.5 times the upper limit of normal, measured within 4 weeks of registration
• Unintentional weight loss >10% over 3 months within 4 weeks of registration
• Severe active co-morbidity defined by:
• Significant history of uncontrolled cardiac disease; i.e. uncontrolled hypertension, unstable angina, myocardial infarction within the last 6 months, uncontrolled congestive heart failure, cardiomyopathy with decreased ejection fraction
• Transmural myocardial infection requiring intravenous antibiotics at the time of registration
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before randomization
• Acquired immune deficiency syndrome (AIDS) based on the current Centre for Disease Control definition; note, however, that HIV testing is not required for entry into this protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chemoradiotherapy; Patients randomized to the standard arm will receive radiotherapy (5x per week) of 60 gray (Gy) in 30 fractions with concurrent cisplatin and etoposide chemotherapy.	Radiation: Chemoradiotherapy; Patients will receive radiotherapy of 60Gy in 30 fractions (5x per week) with concurrent cisplatin and etoposide chemotherapy.
Experimental: Chemoradiotherapy with Integrated Boost Dose; Patients randomized to the experimental arm will receive radiotherapy (5x per week) with an integrated boost dose of up to 85Gy in 30 fractions to tumor subvolumes, with concurrent cisplatin and etoposide chemotherapy.	Radiation: Chemoradiotherapy with Integrated Boost Dose; Patients will receive an RT integrated boost to tumor subvolumes (max boost dose of 85Gy) in 30 fractions (5x per week) with concurrent cisplatin and etoposide chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of local-regional failure rate	Primary outcome of the trial is to determine if dose escalation to metabolically active subvolumes will reduce local-regional failure rate	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	Determine if dose escalation to metabolically active subvolumes will improve progression-free survival at 2 years	2 years
Overall Survival	Determine if dose escalation to metabolically active subvolumes will improve overall survival at 2 years	2 years
Grade 3-5 Toxicity Rate	Determine if dose escalation to metabolically active subvolumes will increase the rate of grade 3-5 toxicities	2 years
Quality of Life FACT-L	Compare the quality of life in the two arms using Functional Assessment of Cancer Therapy-Lung (FACT-L) instrument	2 years
Quality of Life EQ-5D	Compare the quality of life in the two arms using EuroQol Quality of Life-5 Dimensions (EQ-5D) instrument	2 years
Dose-Response Characterization	Characterize the tumor dose-response relationship in the experimental arm and create a tumor control probability model for local-regional failure at 2 years	2 years
Dose Escalation Feasibility	Explore the feasibility of adaptive dose escalation based on PET response at week 2	2 weeks
Imaging Use	Explore the use of Week 0 and Week 2 PET images for prognostication and response assessment for local-regional failure at 2 years	2 years

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute

Publications and helpful links

General Publications

• Raman S, Bissonnette JP, Warner A, Le L, Bratman S, Leighl N, Bezjak A, Palma D, Schellenberg D, Sun A. Rationale and Protocol for a Canadian Multicenter Phase II Randomized Trial Assessing Selective Metabolically Adaptive Radiation Dose Escalation in Locally Advanced Non-small-cell Lung Cancer (NCT02788461). Clin Lung Cancer. 2018 Sep;19(5):e699-e703. doi: 10.1016/j.cllc.2018.05.002. Epub 2018 May 16.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: April 28, 2016
• First Submitted That Met QC Criteria: May 26, 2016
• First Posted (Estimated): June 2, 2016

Study Record Updates

• Last Update Posted (Actual): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• 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: PET-BOOST NSCLC

Plan for Individual participant data (IPD)

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