Non-Small Cell Lung Cancer
Conditions
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.
Interventions
RADIATIONChemoradiotherapy
Patients will receive radiotherapy of 60Gy in 30 fractions (5x per week) with concurrent cisplatin and etoposide chemotherapy.
RADIATIONChemoradiotherapy 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.
Sponsors
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Progression-Free Survival | 2 years | Determine if dose escalation to metabolically active subvolumes will improve progression-free 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 |
| 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 |
| Dose Escalation Feasibility | 2 weeks | Explore the feasibility of adaptive dose escalation based on PET response at week 2 |
| 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 |
| Overall Survival | 2 years | Determine if dose escalation to metabolically active subvolumes will improve overall survival at 2 years |
Countries
Canada
Outcome results
None listed