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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05624996
Other study ID # NRG-LU008
Secondary ID NCI-2022-08263NR
Status Recruiting
Phase Phase 3
First received
Last updated
Start date May 10, 2023
Est. completion date October 15, 2036

Study information

Verified date February 2024
Source NRG Oncology
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase III trial compares the effect of adding stereotactic body radiation therapy (SBRT) to standard treatment (image guided radiation therapy [IGRT] and chemotherapy followed by immunotherapy with durvalumab) versus standard treatment alone in treating patients with non-small cell lung cancer that cannot be treated by surgery (inoperable). SBRT uses special equipment to position a patient and deliver radiation 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 that uses a computer to create picture of the tumor, to help guide the radiation beam during therapy, making it more accurate and causing less damage to healthy tissue. Standard chemotherapy used in this trial consists of combinations of the following drugs: cisplatin, carboplatin, paclitaxel, pemetrexed, and etoposide. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It 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. Paclitaxel is in a class of medications called antimicrotubule agents. It works by stopping the growth and spread of tumor cells. 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 DNA repair and may kill tumor cells. Immunotherapy with durvalumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Adding SBRT to the standard treatment of IGRT with chemotherapy and immunotherapy may be more effective at treating patients with inoperable non-small cell lung cancer than giving the standard treatment alone.


Description:

PRIMARY OBJECTIVES: I. To compare the overall survival in patients with stage II-IIIC inoperable node-positive non-small cell lung cancer (NSCLC) after image guided, motion-managed conventional radiotherapy to the primary tumor and nodal metastases (arm 1) or after image guided, motion-managed stereotactic body radiation therapy (SBRT) to the primary tumor followed by conventionally fractionated radiotherapy to nodal metastases (arm 2) both given with concurrent platinum-based chemotherapy. II. To compare progression-free survival between the experimental arm (arm 2) and control arm (arm 1). SECONDARY OBJECTIVES: I. To compare objective response rate (as defined by Response Evaluation Criteria in Solid Tumors [RECIST] version [v] 1.1) between the experimental arm and control arm. II. To compare the rate of local control between the experimental arm and control arm. III. To compare patterns of failure (primary, locoregional, or distant) between the experimental arm and control arm. IV. To compare changes in pulmonary function (forced expiratory volume in 1 second [FEV1] and diffusion capacity of the lung for carbon monoxide [DLCO] assessed at randomization and at 6 and 12 months following completion of radiation therapy) between the experimental arm and control arm. V. To compare changes in quality of life and patient-reported outcomes assessed from pre-treatment to 3 months following radiation therapy of each treatment arm. VI. To determine acute and late toxicity profiles of each treatment arm as measured by the Common Terminology Criteria for Adverse Events (CTCAE) v5. EXPLORATORY OBJECTIVES: I. To characterize and compare longitudinal quality of life and patient-reported outcomes of each treatment arm. II. To collect biospecimens at baseline, after SBRT (for arm 2 patients), during last 2 weeks of chemoradiation, and after first dose of consolidation therapy, to allow for future analyses. III. To collect 4-dimensional (4D) computed tomography (CT) planning scans and radiation dose to calculate regional lung ventilation and explore pre-treatment 4D-CT based ventilation to predict pulmonary toxicity. IV. To characterize clinical outcomes, toxicities and changes in pulmonary function and quality of life among patients receiving proton and photon radiotherapy. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo conventional IGRT and receive standard of care chemotherapy consisting of paclitaxel intravenously (IV) and carboplatin IV or pemetrexed IV and carboplatin IV or etoposide IV and cisplatin IV or pemetrexed IV and cisplatin IV and then receive durvalumab IV on study. Patients also undergo CT and/or positron emission tomography (PET)/CT during follow up. ARM II: Patients undergo SBRT and conventional IGRT and receive standard of care chemotherapy consisting of paclitaxel IV and carboplatin IV or pemetrexed IV and carboplatin IV or etoposide IV and cisplatin IV or pemetrexed IV and cisplatin IV and then receive durvalumab IV on study. Patients also undergo CT and/or PET/CT during follow up.


Recruitment information / eligibility

Status Recruiting
Enrollment 474
Est. completion date October 15, 2036
Est. primary completion date October 15, 2031
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Pathologically (histologically or cytologically) proven diagnosis of stage II or III (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 - 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 obtain 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 mutation at the time of registration are eligible, and these patients can be treated with consolidation durvalumab or chemotherapy 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 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 which would result in significant overlap of the primary SBRT and nodal radiation fields. 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 chemotherapy regimen, because the treatment in this study may be significantly teratogenic

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Carboplatin
Given IV
Cisplatin
Given IV
Procedure:
Computed Tomography
Undergo CT and/or PET/CT
Biological:
Durvalumab
Given IV
Drug:
Etoposide
Given IV
Radiation:
Image Guided Radiation Therapy
Undergo IGRT
Drug:
Paclitaxel
Given IV
Pemetrexed
Given IV
Procedure:
Positron Emission Tomography
Undergo PET/CT
Other:
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
Radiation:
Stereotactic Body Radiation Therapy
Undergo SBRT

Locations

Country Name City State
United States Hawaii Cancer Care - Westridge 'Aiea Hawaii
United States Pali Momi Medical Center 'Aiea Hawaii
United States Cleveland Clinic Akron General Akron Ohio
United States Atrium Health Stanly/LCI-Albemarle Albemarle North Carolina
United States Mary Greeley Medical Center Ames Iowa
United States McFarland Clinic - Ames Ames Iowa
United States Mission Cancer and Blood - Ankeny Ankeny Iowa
United States Saint Joseph Mercy Hospital Ann Arbor Michigan
United States Anne Arundel Medical Center Annapolis Maryland
United States Langlade Hospital and Cancer Center Antigo Wisconsin
United States Emory Proton Therapy Center Atlanta Georgia
United States Emory Saint Joseph's Hospital Atlanta Georgia
United States Emory University Hospital Midtown Atlanta Georgia
United States Emory University Hospital/Winship Cancer Institute Atlanta Georgia
United States Grady Health System Atlanta Georgia
United States Rush - Copley Medical Center Aurora Illinois
United States UCHealth University of Colorado Hospital Aurora Colorado
United States AIS Cancer Center at San Joaquin Community Hospital Bakersfield California
United States Advocate Good Shepherd Hospital Barrington Illinois
United States Memorial Sloan Kettering Basking Ridge Basking Ridge New Jersey
United States Wilmot Cancer Center at Batavia Batavia New York
United States McLaren Cancer Institute-Bay City Bay City Michigan
United States Sanford Bismarck Medical Center Bismarck North Dakota
United States Illinois CancerCare-Bloomington Bloomington Illinois
United States Saint Joseph Medical Center Bloomington Illinois
United States Saint Joseph Mercy Brighton Brighton Michigan
United States Trinity Health IHA Medical Group Hematology Oncology - Brighton Brighton Michigan
United States Montefiore Medical Center - Moses Campus Bronx New York
United States Montefiore Medical Center-Einstein Campus Bronx New York
United States Montefiore Medical Center-Weiler Hospital Bronx New York
United States Mills-Peninsula Medical Center Burlingame California
United States Aurora Cancer Care-Southern Lakes VLCC Burlington Wisconsin
United States University of Vermont and State Agricultural College Burlington Vermont
United States University of Vermont Medical Center Burlington Vermont
United States Sands Cancer Center Canandaigua New York
United States Cleveland Clinic Mercy Hospital Canton Ohio
United States Illinois CancerCare-Canton Canton Illinois
United States Saint Francis Medical Center Cape Girardeau Missouri
United States Illinois CancerCare-Carthage Carthage Illinois
United States Miami Valley Hospital South Centerville Ohio
United States Centralia Oncology Clinic Centralia Illinois
United States Christiana Care Health System-Concord Health Center Chadds Ford Pennsylvania
United States Chambersburg Hospital Chambersburg Pennsylvania
United States Atrium Health Pineville/LCI-Pineville Charlotte North Carolina
United States Atrium Health University City/LCI-University Charlotte North Carolina
United States Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina
United States Novant Health Presbyterian Medical Center Charlotte North Carolina
United States Saint Joseph Mercy Chelsea Chelsea Michigan
United States Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital Chelsea Michigan
United States Advocate Illinois Masonic Medical Center Chicago Illinois
United States Northwestern University Chicago Illinois
United States McLaren Cancer Institute-Clarkston Clarkston Michigan
United States Morton Plant Hospital Clearwater Florida
United States Wake Forest University at Clemmons Clemmons North Carolina
United States Medical Oncology and Hematology Associates-West Des Moines Clive Iowa
United States Memorial Hospital North Colorado Springs Colorado
United States Rocky Mountain Cancer Centers-Penrose Colorado Springs Colorado
United States UCHealth Memorial Hospital Central Colorado Springs Colorado
United States Memorial Sloan Kettering Commack Commack New York
United States Atrium Health Cabarrus/LCI-Concord Concord North Carolina
United States MD Anderson in The Woodlands Conroe Texas
United States AMG Crystal Lake - Oncology Crystal Lake Illinois
United States Carle at The Riverfront Danville Illinois
United States Geisinger Medical Center Danville Pennsylvania
United States Dayton Blood and Cancer Center Dayton Ohio
United States Dayton Physician LLC-Miami Valley Hospital North Dayton Ohio
United States Miami Valley Hospital Dayton Ohio
United States Miami Valley Hospital North Dayton Ohio
United States Cancer Care Specialists of Illinois - Decatur Decatur Illinois
United States Decatur Memorial Hospital Decatur Illinois
United States Northwestern Medicine Cancer Center Kishwaukee DeKalb Illinois
United States UCHealth - Cherry Creek Denver Colorado
United States Iowa Methodist Medical Center Des Moines Iowa
United States Medical Oncology and Hematology Associates-Des Moines Des Moines Iowa
United States Mission Cancer and Blood - Laurel Des Moines Iowa
United States Wayne State University/Karmanos Cancer Institute Detroit Michigan
United States HSHS Sacred Heart Hospital Eau Claire Wisconsin
United States Carle Physician Group-Effingham Effingham Illinois
United States Crossroads Cancer Center Effingham Illinois
United States Advocate Sherman Hospital Elgin Illinois
United States Ephrata Cancer Center Ephrata Pennsylvania
United States Illinois CancerCare-Eureka Eureka Illinois
United States Sanford Broadway Medical Center Fargo North Dakota
United States Sanford Roger Maris Cancer Center Fargo North Dakota
United States Parkland Health Center - Farmington Farmington Missouri
United States Weisberg Cancer Treatment Center Farmington Hills Michigan
United States McLaren Cancer Institute-Flint Flint Michigan
United States Cancer Care and Hematology-Fort Collins Fort Collins Colorado
United States Poudre Valley Hospital Fort Collins Colorado
United States Atrium Medical Center-Middletown Regional Hospital Franklin Ohio
United States Illinois CancerCare-Galesburg Galesburg Illinois
United States CaroMont Regional Medical Center Gastonia North Carolina
United States Northwestern Medicine Cancer Center Delnor Geneva Illinois
United States Aurora Health Care Germantown Health Center Germantown Wisconsin
United States Adams Cancer Center Gettysburg Pennsylvania
United States Aurora Cancer Care-Grafton Grafton Wisconsin
United States Altru Cancer Center Grand Forks North Dakota
United States UCHealth Greeley Hospital Greeley Colorado
United States Aurora BayCare Medical Center Green Bay Wisconsin
United States Saint Vincent Hospital Cancer Center Green Bay Green Bay Wisconsin
United States Miami Valley Cancer Care and Infusion Greenville Ohio
United States Legacy Mount Hood Medical Center Gresham Oregon
United States Memorial Sloan Kettering Westchester Harrison New York
United States Advocate South Suburban Hospital Hazel Crest Illinois
United States UCHealth Highlands Ranch Hospital Highlands Ranch Colorado
United States Hawaii Cancer Care Inc - Waterfront Plaza Honolulu Hawaii
United States Kuakini Medical Center Honolulu Hawaii
United States Queen's Cancer Cenrer - POB I Honolulu Hawaii
United States Queen's Cancer Center - Kuakini Honolulu Hawaii
United States Queen's Medical Center Honolulu Hawaii
United States Straub Clinic and Hospital Honolulu Hawaii
United States The Cancer Center of Hawaii-Liliha Honolulu Hawaii
United States University of Hawaii Cancer Center Honolulu Hawaii
United States M D Anderson Cancer Center Houston Texas
United States MD Anderson West Houston Houston Texas
United States Novant Health Cancer Institute - Huntersville Huntersville North Carolina
United States Novant Health Presbyterian Medical Center Huntersville Huntersville North Carolina
United States UW Cancer Center Johnson Creek Johnson Creek Wisconsin
United States Aurora Cancer Care-Kenosha South Kenosha Wisconsin
United States Novant Health Cancer Institute - Kernersville Kernersville North Carolina
United States Illinois CancerCare-Kewanee Clinic Kewanee Illinois
United States Karmanos Cancer Institute at McLaren Greater Lansing Lansing Michigan
United States Sparrow Hospital Lansing Michigan
United States McLaren Cancer Institute-Lapeer Region Lapeer Michigan
United States MD Anderson League City League City Texas
United States Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center Lebanon New Hampshire
United States Sechler Family Cancer Center Lebanon Pennsylvania
United States Geisinger Medical Oncology-Lewisburg Lewisburg Pennsylvania
United States University of Kentucky/Markey Cancer Center Lexington Kentucky
United States AMG Libertyville - Oncology Libertyville Illinois
United States Condell Memorial Hospital Libertyville Illinois
United States Trinity Health Saint Mary Mercy Livonia Hospital Livonia Michigan
United States UCHealth Lone Tree Health Center Lone Tree Colorado
United States Los Angeles General Medical Center Los Angeles California
United States USC / Norris Comprehensive Cancer Center Los Angeles California
United States Medical Center of the Rockies Loveland Colorado
United States Illinois CancerCare-Macomb Macomb Illinois
United States University of Wisconsin Carbone Cancer Center Madison Wisconsin
United States Aurora Bay Area Medical Group-Marinette Marinette Wisconsin
United States Fremont - Rideout Cancer Center Marysville California
United States Levine Cancer Institute - Union West Matthews North Carolina
United States Matthews Radiation Oncology Center Matthews North Carolina
United States Novant Health Cancer Institute - Matthews Matthews North Carolina
United States Carle Physician Group-Mattoon/Charleston Mattoon Illinois
United States Froedtert Menomonee Falls Hospital Menomonee Falls Wisconsin
United States Memorial Sloan Kettering Monmouth Middletown New Jersey
United States Aurora Cancer Care-Milwaukee Milwaukee Wisconsin
United States Aurora Saint Luke's Medical Center Milwaukee Wisconsin
United States Aurora Sinai Medical Center Milwaukee Wisconsin
United States Medical College of Wisconsin Milwaukee Wisconsin
United States Zablocki Veterans Administration Medical Center Milwaukee Wisconsin
United States Atrium Health Union/LCI-Union Monroe North Carolina
United States Memorial Sloan Kettering Bergen Montvale New Jersey
United States Novant Health Cancer Institute - Mooresville Mooresville North Carolina
United States Novant Health Cancer Institute - Mount Airy Mount Airy North Carolina
United States McLaren Cancer Institute-Macomb Mount Clemens Michigan
United States ProHealth D N Greenwald Center Mukwonago Wisconsin
United States Memorial Sloan Kettering Cancer Center New York New York
United States New York Proton Center New York New York
United States Christiana Care Health System-Christiana Hospital Newark Delaware
United States Helen F Graham Cancer Center Newark Delaware
United States Medical Oncology Hematology Consultants PA Newark Delaware
United States Cancer Care Center of O'Fallon O'Fallon Illinois
United States Drexel Town Square Health Center Oak Creek Wisconsin
United States Advocate Christ Medical Center Oak Lawn Illinois
United States ProHealth Oconomowoc Memorial Hospital Oconomowoc Wisconsin
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Vince Lombardi Cancer Clinic - Oshkosh Oshkosh Wisconsin
United States Illinois CancerCare-Ottawa Clinic Ottawa Illinois
United States Advocate Lutheran General Hospital Park Ridge Illinois
United States Illinois CancerCare-Pekin Pekin Illinois
United States Illinois CancerCare-Peoria Peoria Illinois
United States Methodist Medical Center of Illinois Peoria Illinois
United States Mercy Health Perrysburg Cancer Center Perrysburg Ohio
United States Illinois CancerCare-Peru Peru Illinois
United States McLaren Cancer Institute-Northern Michigan Petoskey Michigan
United States Thomas Jefferson University Hospital Philadelphia Pennsylvania
United States University of Pennsylvania/Abramson Cancer Center Philadelphia Pennsylvania
United States Cancer Center at Saint Joseph's Phoenix Arizona
United States 21st Century Oncology-Pontiac Pontiac Michigan
United States Saint Joseph Mercy Oakland Pontiac Michigan
United States McLaren-Port Huron Port Huron Michigan
United States Legacy Good Samaritan Hospital and Medical Center Portland Oregon
United States Illinois CancerCare-Princeton Princeton Illinois
United States Aurora Cancer Care-Racine Racine Wisconsin
United States Renown Regional Medical Center Reno Nevada
United States Ascension Saint Mary's Hospital Rhinelander Wisconsin
United States Highland Hospital Rochester New York
United States University of Rochester Rochester New York
United States Wilmot Cancer Institute Radiation Oncology at Greece Rochester New York
United States Levine Cancer Institute-Rock Hill Rock Hill South Carolina
United States Rock Hill Radiation Therapy Center Rock Hill South Carolina
United States Sutter Cancer Centers Radiation Oncology Services-Roseville Roseville California
United States Sutter Roseville Medical Center Roseville California
United States William Beaumont Hospital-Royal Oak Royal Oak Michigan
United States Sutter Medical Center Sacramento Sacramento California
United States Coborn Cancer Center at Saint Cloud Hospital Saint Cloud Minnesota
United States Norris Cotton Cancer Center-North Saint Johnsbury Vermont
United States Mercy Hospital Saint Louis Saint Louis Missouri
United States Mercy Hospital South Saint Louis Missouri
United States Missouri Baptist Medical Center Saint Louis Missouri
United States Sainte Genevieve County Memorial Hospital Sainte Genevieve Missouri
United States Novant Health Cancer Institute - Rowan Salisbury North Carolina
United States Rowan Regional Medical Center Salisbury North Carolina
United States California Pacific Medical Center-Pacific Campus San Francisco California
United States Mills Health Center San Mateo California
United States Saint Vincent Hospital Cancer Center at Sheboygan Sheboygan Wisconsin
United States Vince Lombardi Cancer Clinic-Sheboygan Sheboygan Wisconsin
United States Atrium Health Cleveland/LCI-Cleveland Shelby North Carolina
United States Sanford Cancer Center Oncology Clinic Sioux Falls South Dakota
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States Memorial Medical Center Springfield Illinois
United States Southern Illinois University School of Medicine Springfield Illinois
United States Springfield Clinic Springfield Illinois
United States Novant Health Cancer Institute - Statesville Statesville North Carolina
United States Wake Forest Baptist Health - Hematology Oncology - Statesville Statesville North Carolina
United States Ascension Saint Michael's Hospital Stevens Point Wisconsin
United States Saint Vincent Hospital Cancer Center at Sturgeon Bay Sturgeon Bay Wisconsin
United States MD Anderson in Sugar Land Sugar Land Texas
United States Missouri Baptist Sullivan Hospital Sullivan Missouri
United States Aurora Medical Center in Summit Summit Wisconsin
United States BJC Outpatient Center at Sunset Hills Sunset Hills Missouri
United States Novant Cancer Institute Radiation Oncology - Supply Supply North Carolina
United States Novant Health Cancer Institute - Thomasville Thomasville North Carolina
United States Munson Medical Center Traverse City Michigan
United States Upper Valley Medical Center Troy Ohio
United States William Beaumont Hospital - Troy Troy Michigan
United States Legacy Meridian Park Hospital Tualatin Oregon
United States Banner University Medical Center - Tucson Tucson Arizona
United States University of Arizona Cancer Center-North Campus Tucson Arizona
United States Memorial Sloan Kettering Nassau Uniondale New York
United States Carle Cancer Center Urbana Illinois
United States Westchester Medical Center Valhalla New York
United States Legacy Cancer Institute Medical Oncology and Day Treatment Vancouver Washington
United States Legacy Salmon Creek Hospital Vancouver Washington
United States Northwestern Medicine Cancer Center Warrenville Warrenville Illinois
United States Illinois CancerCare - Washington Washington Illinois
United States UW Cancer Center at ProHealth Care Waukesha Wisconsin
United States Aspirus Regional Cancer Center Wausau Wisconsin
United States Aurora Cancer Care-Milwaukee West Wauwatosa Wisconsin
United States Wilmot Cancer Institute at Webster Webster New York
United States Aurora West Allis Medical Center West Allis Wisconsin
United States Froedtert West Bend Hospital/Kraemer Cancer Center West Bend Wisconsin
United States Reading Hospital West Reading Pennsylvania
United States Ascension Via Christi Hospitals Wichita Wichita Kansas
United States Geisinger Wyoming Valley/Henry Cancer Center Wilkes-Barre Pennsylvania
United States Novant Health Cancer Institute - Wilkesboro Wilkesboro North Carolina
United States Wake Forest Baptist Health - Wilkes Medical Center Wilkesboro North Carolina
United States Asplundh Cancer Pavilion Willow Grove Pennsylvania
United States Novant Health Cancer Institute Radiation Oncology - Wilmington Wilmington North Carolina
United States Novant Health New Hanover Regional Medical Center Wilmington North Carolina
United States Novant Health Forsyth Medical Center Winston-Salem North Carolina
United States Wake Forest University Health Sciences Winston-Salem North Carolina
United States Aspirus Cancer Care - Wisconsin Rapids Wisconsin Rapids Wisconsin
United States WellSpan Health-York Cancer Center York Pennsylvania
United States WellSpan Health-York Hospital York Pennsylvania
United States Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus Ypsilanti Michigan

Sponsors (2)

Lead Sponsor Collaborator
NRG Oncology National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Functional mean lung dose Collection of 4 dimensional (4D) CT planning CTs and calculation of radiation dose to regional lung ventilation will be performed among randomized patients with 4D CT planning CTs. To evaluate functional dose metrics, ventilation maps will be registered to the average 4DCT reference frame. Functional dose metrics and standard dose metrics will be calculated and evaluated. Functional mean lung dose will be defined as the mean dose delivered to functional lung. Dose to total lung and dose to functional lung will then be correlated with pulmonary toxicity including grade 2 or higher radiation pneumonitis or any grade 3 or higher cough, dyspnea, hypoxia or respiratory failure. Logistic regression models will be used to explore the correlation between pulmonary toxicity and functional mean lung dose. Up to 8 years
Other Incidence of toxicities Descriptive analyses will be reported, based on corresponding analysis plans within patients who actually receive proton and photon radiotherapy (e.g., per-protocol population), respectively. Up to 8 years
Primary Overall Survival (OS) 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. Between date of randomization and date of death due to any cause, assessed up to 8 years
Primary Progression-Free Survival (PFS) 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. Between date of randomization and first date of documented progression or death due to any cause, assessed up to 8 years
Secondary Objective Response Rate (ORR) ORR (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) is defined as the number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR) and will be based on all randomized patients who have measurable disease. Therefore, data obtained up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR. The ORR will be compared between arm 2 versus arm 1 using a Fisher's exact test. A binary response variable for ORR will be used for the analysis with the categories of CR and PR versus stable disease (SD), progressive disease (PD) and inevaluable (NE). Up to 8 years
Secondary Time to progression Local control will be defined as freedom from local progression, in which a failure is defined as intrathoracic tumor progression (failure in the lobe of the primary tumor or mediastinal lymph nodes) by RECIST 1.1 criteria. Local control will be analyzed as competing risks data based on cause-specific hazards approaches, where deaths without local failure will be considered as a competing event and analyzed as "censoring" of local failure. The rates at various timepoints (e.g., every 6 months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method. The associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided. Up to 8 years
Secondary Time to primary, locoregional, or distant failure Competing risks analysis will be used to analyze times to primary failure, locoregional failure and distant failure as the first failure. Competing events include primary failure, locoregional failure, distant failure and deaths without any failures. Rates at various timepoints (i.e., every 6 months after randomization) for each arm will be estimated using the cumulative incidence function. The associated 95% CI will be calculated using the Delta method and based on a log-log transformation applied on the estimated cumulative incidence functions. Statistical inferences of the development of each failure between arms will be based on cause-specific hazards using the log-rank test and Cox proportional hazard model. In addition, Gray's test and the Fine-Gray model will also be used to provide statistical inferences between arms based on cumulative incidence functions and subdistribution hazards. Up to 8 years
Secondary Changes in pulmonary function Includes forced expiratory volume in 1 second (FEV1) and diffusion capacity of the lung for carbon monoxide (DLCO). Changes in pulmonary function (FEV1 and DLCO) will be summarized with descriptive statistics, and compared with Wilcoxon rank-sum test. The descriptive statistics of changes in FEV1 and diffusion capacity before and after treatment will be reported by treatment arm and by response categories (complete response; partial response; stable disease; progressive disease). Linear regression will be used to model changes with adjustment for treatment arms and possibly other baseline covariates, if applicable. The grade 3-5 NRG Oncology Pulmonary Toxicity Scale for changes will be reported with the frequency and grade by arm. Logistic regression will be used to model the distribution of the NRG Oncology Pulmonary Toxicity Scale by arms with and without adjustment for covariates. From randomization to 6 months or 12 months
Secondary Patient Reported Outcomes Functional Assessment of Cancer Therapy Lung Questionnaire trial outcome index deterioration rates at 3 months and associated 95% confidence interval will be calculated for each treatment group, based on all randomized subjects. Clopper-Pearson method will be used for calculating 95% CI. The deterioration rates of each arm will also be compared using Cochran-Mantel-Haenszel Test, stratified by PD-L1 expression and T-stage. At 3, 12, and 24 months
Secondary Incidence of adverse events For each patient, the maximum severity reported will be used in the summaries. Adverse events will be summarized regardless of relationship to protocol treatment as assessed by the investigator. Treatment-related adverse events using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) will be presented in statistical analysis reports/publications in CTCAE version 5. Adverse event rates will be reported with the frequency and severity (e.g., type, grade, and attribution) by arm. Up to 8 years
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