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

Not Applicable

Active, not recruiting

• Conditions: Non-Small Cell Lung Cancer

• Registration Number: NCT02788461
• Lead Sponsor: Lawson Health Research Institute

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-04-28
• Study Start: 2016-05
• Study First Submitted QC: 2016-05-26
• Study First Posted: 2016-06-02
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-27
• Last Update Posted: 2024-02-29
• Primary Completion: 2025-04
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 78

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (7)

London Regional Cancer Program; 🇨🇦 London, Ontario, Canada

Stronach Regional Cancer Centre at Southlake Regional Health Centre; 🇨🇦 Newmarket,, Ontario, Canada

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Kingston General Hospital; 🇨🇦 Kingston, Ont, Canada

McGill University Health Centre, Glen site Cedars Cancer Center; 🇨🇦 Montreal,, Quebec, Canada

CHUS - Hôpital Fleurimont; 🇨🇦 Sherbrooke, Quebec, Canada

CHU de Quebec - L'Hôtel-Dieu de Québec; 🇨🇦 Quebec, Canada