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

Interventions: Radiation: Chemoradiotherapy
Radiation: Chemoradiotherapy with Integrated Boost Dose

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Chemoradiotherapy	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.
Chemoradiotherapy with Integrated Boost Dose	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.

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

Locations (7): London Regional Cancer Program
🇨🇦
London, Ontario, Canada
Kingston General Hospital
🇨🇦
Kingston, Ont, Canada
Princess Margaret Cancer Centre
🇨🇦
Toronto, Ontario, Canada
CHUS - Hôpital Fleurimont
🇨🇦
Sherbrooke, Quebec, Canada
CHU de Quebec - L'Hôtel-Dieu de Québec
🇨🇦
Quebec, Canada
McGill University Health Centre, Glen site Cedars Cancer Center
🇨🇦
Montreal,, Quebec, Canada
Stronach Regional Cancer Centre at Southlake Regional Health Centre
🇨🇦
Newmarket,, Ontario, Canada