Condition

• Lung Non-Small Cell Carcinoma

Eligibility

Eligible Ages

Over 18 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

- Histopathologic diagnosis of NSCLC, may have mixed or multiple histologies but no
small cell component

- No known EGFR mutation or ALK rearrangement

- No metastatic disease (M0) per most recent PET/CT and head CT/MRI imaging

- No disease progression per CT chest (including upper abdomen as per standard
practice) with intravenous (IV) contrast (unless IV contrast is contraindicated) or
FDG-PET performed post-neoadjuvant therapy ≤ 90 days prior to registration, either
before or after surgery

- No metastatic disease (M0) per head CT/MRI imaging

- Prior treatment with 2-4 cycles of neoadjuvant systemic therapy with any guideline
(National Comprehensive Cancer Network [NCCN]) concordant regimen

- Lobectomy or greater oncologic surgical resection within 8 weeks prior to
registration

- Complete (R0) resection showing ypN2 disease

- No prior radiotherapy to the lungs or mediastinum

- No treatment with a VEGF inhibitor ≤ 90 days prior to registration or plan to treat
with adjuvant systemic therapy including a VEGF inhibitor

- Age ≥ 18 years

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

- Absolute neutrophil count (ANC) ≥ 1,000/mm^3

- Platelet count ≥ 50,000/mm^3

- Calculated (Calc.) creatinine clearance ≥ 30 mL/min

- Total bilirubin ≤ 3 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT])
≤ 5 x upper limit of normal (ULN)

- Not pregnant, because this study involves radiation therapy, which has known
genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing
potential only, a negative urine or serum pregnancy test done ≤ 7 days prior to
registration is required

- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial

- Cardiac function: Patients with known history or current symptoms of cardiac
disease, or history of treatment with cardiotoxic agents, should have a clinical
risk assessment of cardiac function using the New York Heart Association Functional
Classification. To be eligible for this trial, patients should be class 2B or better

- No idiopathic pulmonary fibrosis requiring anti-fibrotic medication: Patients with
idiopathic pulmonary fibrosis or inflammatory/interstitial lung disease compromising
pulmonary function or requiring ongoing treatment with nintedanib, pirfenidone, or
other anti-fibrotic drug are excluded

- HIV-infected patients on effective anti-retroviral therapy with an undetectable
viral load within 6 months are eligible for this trial

Recruiting Locations

Study Contact

Detailed Description

PRIMARY OBJECTIVES: I. To assess whether intensity-modulated post-operative radiation therapy (I²-PORT) improves disease-free survival (DFS) of patients with R0 resected ypN2 NSCLC compared to standard of care (SOC). II. To assess whether I²-PORT does not unacceptably increase (by ≥ 6.5 percentage points) the rate of severe (grade ≥ 3 per Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5) late cardiopulmonary toxicity compared to SOC. SECONDARY OBJECTIVES: I. 5-year DFS, 2- and 5-year overall survival (OS). II. Local versus (vs.) regional control, rate of distant metastases. III. Acute and late adverse events (AE) rates of specific cardiac, pulmonary, and other toxicities, per CTCAE version 5.0. IV. Rates of non-mild, moderate, or severe-very severe symptoms per Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE), particularly terms related to cardiopulmonary toxicities, e.g., pain, shortness of breath, cough, wheezing, and heart palpitations. V. Subset analyses by single vs. multi-station N2 and by adequacy of surgical nodal evaluation. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI), fludeoxyglucose-positron emission tomography (FDG-PET), and blood sample collection throughout the study. ARM II: Patients undergo I²-PORT once daily (QD) Monday through Friday over 15-25 fractions over 5-6 weeks, starting 4-12 weeks after surgery. Radiation simulation should be performed within 21 days of starting I²-PORT. Starting 1-42 days after completion of I²-PORT, patients receive SOC chemotherapy or immunotherapy on the study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years, and then every 6 months for 3 years.