This phase III trial compares the effect of adding stereotactic body radiation therapy (SBRT) to the usual treatment (conventional image guided radiation therapy \[IGRT\] and chemotherapy followed by immunotherapy with durvalumab or targeted therapy with osimertinib) versus the usual treatment alone in treating patients with non-small cell lung cancer that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be treated by surgery (inoperable). SBRT uses special equipment to position a patient and deliver radiation therapy to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. IGRT is a type of radiation therapy that creates a picture of the tumor to help guide the radiation beam during therapy, making it more accurate and causing less damage to healthy tissue. Usual chemotherapy used in this trial consists of combinations of the following drugs: cisplatin, carboplatin, paclitaxel, nab-paclitaxel, pemetrexed, and etoposide. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds. Cisplatin works by killing, stopping, or slowing the growth of tumor cells. Carboplatin works in a way similar to the anticancer drug cisplatin but may be better tolerated than cisplatin. Carboplatin works by killing, stopping, or slowing the growth of tumor cells as well. Paclitaxel is in a class of medications called antimicrotubule agents. It works by stopping the growth and spread of tumor cells. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by blocking the action of a certain substance in the body that may help tumor cells multiply. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill tumor cells. Immunotherapy with durvalumab can induce changes in the body's immune system and can interfere with the ability of tumor cells to grow and spread. Osimertinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called EGFR that signals cancer cells to multiply. This helps slow or stop the spread of tumor cells. Adding SBRT to the usual treatment of IGRT with chemotherapy and immunotherapy may be more effective at treating patients with locally-advanced non-small cell lung cancer than giving the usual treatment alone.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of non-operable stage IIB or III, node positive (American Joint Committee on Cancer \[AJCC\] eighth edition) non-small cell lung cancer (NSCLC) with known PD-L1 status prior to registration
* Patients must have an identified primary tumor and at least one nodal metastasis (peribronchial/hilar/intrapulmonary, mediastinal/subcarinal, supraclavicular/scalene)
* Up to 4 cycles of systemic therapy received prior to registration for the current study cancer is allowable; any prior chemotherapy for a different cancer is also permissible
* Patients who refuse surgery, in addition to those who are technically unresectable or medically inoperable, are eligible.
* Patients with separate tumor nodules in the same lobe of the primary tumor are eligible
* The patient must be deemed clinically appropriate for curative intent definitive combined modality therapy, based on the following staging assessments:
* History/physical examination prior to registration;
* Magnetic resonance imaging (MRI) scan of the brain (preferred) or CT scan of the brain (if available, contrast is preferred for all neuroimaging) prior to registration;
* CT chest with IV contrast (if contrast is available and unless contraindicated, such as for abnormal kidney function) prior to registration. PET/CT may be used if the CT portion is of identical diagnostic quality as achieved in a stand-alone CT
* No evidence of distant metastases based on FDG PET/CT scan obtained within 60 days of registration
* Primary tumor =\< 7 cm
* Age \>= 18
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Hematologic function (e.g. platelets, leukocytes, hemoglobin) amenable, at the discretion of the treating physician, to allow for treatment with chemotherapy and concurrent radiation therapy
* Creatinine clearance \>= 25 mL/min by the Cockcroft-Gault (C-G) equation
* Subjects with non-malignant pleural effusion are eligible provided the effusion is not known or demonstrated to be an exudative effusion
* If a pleural effusion is present, the following criteria must be met to exclude malignant involvement:
* When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative;
* Effusions that are minimal (i.e., not visible on chest x-ray) that are too small to safely tap are eligible
* Medical history consistent with the patient being amenable, at the discretion of the treating physician, to allow for treating with consolidation immunotherapy. Patients with known EGFR/ALK/other driver mutation at the time of registration are eligible, and these patients can be treated with consolidation systemic therapy at the discretion of the treating physician
* 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
* Negative pregnancy test =\< 14 days prior to registration for participants of childbearing potential
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
* Prior radiotherapy to the study cancer (local recurrence). Prior radiotherapy for a different cancer/condition to the region of the study cancer that would result in overlap of radiation therapy fields that is determined by the treating physician to impede the treatment of the study malignancy
* Patients without identifiable primary tumor and at least 1 pathologically enlarged lymph node are not eligible (T3-4N0 or T0N1-3 patients are not eligible). At least 1 radiographically-involved lymph node is required, but pathologic confirmation of involvement is not mandated
* Centrally located primary tumor \< 2 cm from involved nodal disease that would result in significant overlap of the primary SBRT and nodal radiation fields. This does not include proximity to involved segmental and subsegmental lymph nodes (levels 13 and 14) that would not result in overlap of dose to the proximal bronchial tree or esophagus. Centrally located is defined as within or touching the zone of the proximal bronchial tree, which is a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus right and left lower lobe bronchi)
* Participants who are pregnant or unwilling to discontinue nursing
* Participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) unwilling to use highly effective contraceptives during therapy and for the Food and Drug Administration (FDA)-labeled contraception timeframe required after the final dose of the selected systemic therapy regimen, because the treatment in this study may be significantly teratogenic
Primary outcome measure(s)
Overall survival (OS) — Time between date of randomization and date of death due to any cause, assessed up to 8 years Non-inferiority (NI) between arm 2 and arm 1 (reference level) will be evaluated by comparing the upper bound of the 95% confidence interval for the hazard ratio to the pre-specified NI margin. NI of arm 2 will be concluded if the upper bound of the confidence interval is equal to, or falls below, the pre-specified margin at the final analysis. When evaluating the NI of arm 2 in OS, a Cox proportional hazards (PH) model stratified by stratification factors will be used to compute the hazard ratio and associated 95% confidence interval (CI). OS rates will be estimated using the Kaplan-Meier method. If the NI of arm 2 in OS is demonstrated, the superiority of arm 1 in OS will be tested at 1-sided significance level of 0.025 using a stratified log-rank test by adjusting for stratification factors.
Progression-free survival (PFS) — Time between date of randomization and first date of documented progression or death due to any cause, assessed up to 8 years The PFS analysis will be conducted using the same methods and stratification factors as the OS analysis. The superiority of arm 2 in PFS will be tested at 1-sided significance level of 0.025 using a stratified log-rank test by adjusting for stratification factors. In the event that the NI of OS is not established, statistical inference of PFS will be considered exploratory in nature only. A Cox PH model stratified by stratification factors will be used to compute the hazard ratio and associated 95% CI.
Trial sites (477)
Facility
City
Region
Status
University of Alabama at Birmingham Cancer Center
Birmingham
Alabama
Recruiting
The Kirklin Clinic at Acton Road
Birmingham
Alabama
Recruiting
Gulf Health Hospitals Inc/Infirmary Cancer Care - Malbis
Daphne
Alabama
Recruiting
Thomas Hospital
Fairhope
Alabama
Recruiting
Mobile Infirmary Medical Center
Mobile
Alabama
Recruiting
Gulf Health Hospitals Inc/Infirmary Cancer Care - Saraland
Saraland
Alabama
Recruiting
Kingman Regional Medical Center
Kingman
Arizona
Recruiting
Cancer Center at Saint Joseph's
Phoenix
Arizona
Recruiting
Mayo Clinic Hospital in Arizona
Phoenix
Arizona
Recruiting
Banner University Medical Center - Tucson
Tucson
Arizona
Recruiting
University of Arizona Cancer Center-North Campus
Tucson
Arizona
Recruiting
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro
Arkansas
Recruiting
University of Arkansas for Medical Sciences
Little Rock
Arkansas
Recruiting
AIS Cancer Center at San Joaquin Community Hospital
Bakersfield
California
Recruiting
Mills-Peninsula Medical Center
Burlingame
California
Recruiting
Palo Alto Medical Foundation-Fremont
Fremont
California
Recruiting
Los Angeles General Medical Center
Los Angeles
California
Active Not Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles
California
Active Not Recruiting
Fremont - Rideout Cancer Center
Marysville
California
Terminated
Memorial Medical Center
Modesto
California
Recruiting
Palo Alto Medical Foundation-Camino Division
Mountain View
California
Recruiting
Palo Alto Medical Foundation Health Care
Palo Alto
California
Recruiting
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville
California
Recruiting
Sutter Roseville Medical Center
Roseville
California
Recruiting
Sutter Medical Center Sacramento
Sacramento
California
Recruiting
California Pacific Medical Center-Pacific Campus
San Francisco
California
Recruiting
Mills Health Center
San Mateo
California
Recruiting
Sutter Pacific Medical Foundation
Santa Rosa
California
Recruiting
Palo Alto Medical Foundation-Sunnyvale
Sunnyvale
California
Recruiting
Sutter Solano Medical Center/Cancer Center
Vallejo
California
Recruiting
UCHealth University of Colorado Hospital
Aurora
Colorado
Recruiting
Rocky Mountain Cancer Centers-Penrose
Colorado Springs
Colorado
Recruiting
UCHealth Memorial Hospital Central
Colorado Springs
Colorado
Recruiting
Memorial Hospital North
Colorado Springs
Colorado
Recruiting
UCHealth - Cherry Creek
Denver
Colorado
Recruiting
Poudre Valley Hospital
Fort Collins
Colorado
Recruiting
Cancer Care and Hematology-Fort Collins
Fort Collins
Colorado
Recruiting
UCHealth Greeley Hospital
Greeley
Colorado
Recruiting
UCHealth Highlands Ranch Hospital
Highlands Ranch
Colorado
Recruiting
UCHealth Lone Tree Health Center
Lone Tree
Colorado
Recruiting
+ 437 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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