A Study of Targeted Post-Surgery Radiation Therapy for Non-Small Cell Lung Cancer With Remaining Lymph Node Cancer After Treatment
Purpose
This phase II trial compares the effect of intensity-modulated post-operative radiation therapy (I²-PORT) followed by standard of care therapy (chemotherapy or immunotherapy) to standard of care therapy alone in treating patients with non-small cell lung cancer (NSCLC) who have remaining lymph node cancer after surgery. Radiation therapy uses high-energy X-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Intensity-modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Adding I²-PORT radiation therapy to standard therapy may be more effective than standard therapy alone in reducing the risk of cancer returning in those who have undergone surgery for NSCLC.
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
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Arm I (SOC chemotherapy/immunotherapy) |
Patients receive SOC chemotherapy or immunotherapy on 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. |
|
|
Experimental Arm II (I²-PORT, SOC chemotherapy/immunotherapy) |
Patients undergo I²-PORT QD Monday through Friday over 15-25 fractions over 5-6 weeks. Starting 1-42 days after completion of I²-PORT, patients receive SOC chemotherapy or immunotherapy on 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. |
|
Recruiting Locations
Jonesboro, Arkansas 72401
Decatur, Illinois 62526
Decatur, Illinois 62526
O'Fallon, Illinois 62269
O'Fallon, Illinois 62269
Ann Arbor, Michigan 48106
Brighton, Michigan 48114
Brighton, Michigan 48114
Canton, Michigan 48188
Canton, Michigan 48188
Chelsea, Michigan 48118
Chelsea, Michigan 48118
Livonia, Michigan 48154
Ypsilanti, Michigan 48197
Brainerd, Minnesota 56401
Deer River, Minnesota 56636
Duluth, Minnesota 55805
Duluth, Minnesota 55805
Duluth, Minnesota 55805
Hibbing, Minnesota 55746
Site Public Contact
218-786-3308
Sandstone, Minnesota 55072
Virginia, Minnesota 55792
Southhaven, Mississippi 38671
The Bronx, New York 10461
The Bronx, New York 10467
Chapel Hill, North Carolina 27599
Collierville, Tennessee 38017
Memphis, Tennessee 38120
Ashland, Wisconsin 54806
Ashland, Wisconsin 54806
Hayward, Wisconsin 54843
Spooner, Wisconsin 54801
Superior, Wisconsin 54880
Site Public Contact
701-364-6272
More Details
- Status
- Recruiting
- Sponsor
- Alliance for Clinical Trials in Oncology
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.