A Randomized Phase II/III Trial of Modern Immunotherapy Based Systemic Therapy With or Without Radiation Therapy for PD-L1-Negative, Advanced Non-Small Cell Lung Cancer

Who is this study for? Patients with PD-L1-negative, advanced non-small cell lung cancer
Status: Recruiting
Location: See all (151) locations...
Intervention Type: Other, Procedure, Biological, Radiation
Study Type: Interventional
Study Phase: Phase 2/Phase 3
SUMMARY

This phase II/III trial compares the addition of radiation therapy to the usual treatment (immunotherapy with or without chemotherapy) versus (vs.) usual treatment alone in treating patients with non-small cell lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic) whose tumor is also negative for a molecular marker called PD-L1. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The addition of radiation therapy to usual treatment may stop the cancer from growing and increase the life of patients with advanced non-small cell lung cancer who are PD-L1 negative.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Histologic or cytologic diagnosis of stage IV NSCLC using version American Joint Committee on Cancer (AJCC) 8th edition (includes M1a, M1b, and M1c stage disease). Patients with stage IIIB and IIIC disease are eligible if they are not a candidate for combined chemotherapy and radiation

• PD-L1 expression tumor proportion score (TPS) \< 1% in tumor cells. If PD-L1 expression TPS is unevaluable or the testing could not be completed patients are not eligible. The assay must have been performed locally by a Clinical Laboratory Improvement Act (CLIA) (or equivalent) certified laboratory. The type of assay will be recorded

• For non-squamous patients only (adenocarcinoma or adenosquamous): EGFR, ALK and ROS1 testing must be done locally. No patients with known actionable EGFR mutations (except exon 20 insertion), ALK or ROS1 mutations that can be treated with oral tyrosine inhibitors

• Measurable disease based on RECIST 1.1, including at least two cancerous deposits. At least one deposit must be RECIST measurable (and not to be irradiated) while at least one OTHER deposit (measurable or non-measurable) must meet criteria for three 8 gray (Gy) doses of radiation

• Age \>= 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• No more than three weeks of treatment with systemic chemotherapy or immunotherapy for advanced NSCLC

• No more than three weeks of treatment with checkpoint inhibitors for metastatic lung cancer

• No treatment with chemotherapy or immunotherapy for non-metastatic disease (e.g., adjuvant therapy) within 6 months prior to registration

• No systemic immunostimulatory or immunosuppressive drugs, including \> 10 mg prednisone equivalent per day, within 2 weeks or 5 half-live of the drug, whichever is shorter. Steroid premedication per local standard is allowed

• \>= 1 week prior to registration since palliative (including central nervous system \[CNS\]) radiotherapy to any tumor site

• No prior allogeneic tissue/solid organ transplant

• No uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance with study requirements

• No current pneumonitis or history of non-infectious pneumonitis that required steroids

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration

• No active auto-immune disease that requires systemic therapy within 2 years prior to registration. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed

• No known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known hepatitis C virus (defined as HCV ribonucleic acid \[RNA\] \[qualitative\] is detected) infection

• No patients with symptomatic central nervous system metastases and/or carcinomatous meningitis. Patients with small asymptomatic brain metastases are eligible as are patients with treated brain metastases that require no steroids

• Not pregnant and not nursing, because this study involves radiation as well as potentially chemotherapy which have 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

• No patients with a currently active second malignancy that is progressing or has required active treatment within the last 2 years. Participants with non-melanoma skin cancers or carcinoma in-situ (e.g., breast carcinoma, urothelial carcinoma or cervical cancer in situ) or localized prostate cancer (T1-3, N0, M0) that have undergone potentially curative therapy are eligible

• No hypersensitivity (\>= grade 3) to immunotherapy and/or any of its excipients

• No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g.,FluMist \[registered trademark\]) are live attenuated vaccines and are not allowed. COVID-19 vaccine is allowed

• Absolute neutrophil count (ANC) \>= 1,500/mm\^3

• Platelet count \>= 100,000/mm\^3

• Calculated (Calc.) creatinine clearance \>= 45 mL/min

• Total bilirubin =\< 1.5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN)

Locations
United States
Arkansas
University of Arkansas for Medical Sciences
RECRUITING
Little Rock
Arizona
Mayo Clinic Hospital in Arizona
ACTIVE_NOT_RECRUITING
Phoenix
California
Alta Bates Summit Medical Center-Herrick Campus
RECRUITING
Berkeley
City of Hope Comprehensive Cancer Center
RECRUITING
Duarte
City of Hope at Irvine Lennar
RECRUITING
Irvine
City of Hope Antelope Valley
RECRUITING
Lancaster
Fremont - Rideout Cancer Center
RECRUITING
Marysville
Memorial Medical Center
RECRUITING
Modesto
Providence Queen of The Valley
RECRUITING
Napa
University of California Davis Comprehensive Cancer Center
RECRUITING
Sacramento
City of Hope South Pasadena
RECRUITING
South Pasadena
Gene Upshaw Memorial Tahoe Forest Cancer Center
RECRUITING
Truckee
City of Hope Upland
RECRUITING
Upland
Colorado
Memorial Hospital North
ACTIVE_NOT_RECRUITING
Colorado Springs
UCHealth Memorial Hospital Central
ACTIVE_NOT_RECRUITING
Colorado Springs
Cancer Care and Hematology-Fort Collins
ACTIVE_NOT_RECRUITING
Fort Collins
Poudre Valley Hospital
ACTIVE_NOT_RECRUITING
Fort Collins
UCHealth Greeley Hospital
ACTIVE_NOT_RECRUITING
Greeley
Medical Center of the Rockies
ACTIVE_NOT_RECRUITING
Loveland
Washington, D.c.
MedStar Washington Hospital Center
ACTIVE_NOT_RECRUITING
Washington
Delaware
Beebe South Coastal Health Campus
RECRUITING
Millville
Helen F Graham Cancer Center
RECRUITING
Newark
Medical Oncology Hematology Consultants PA
RECRUITING
Newark
Beebe Health Campus
RECRUITING
Rehoboth Beach
Florida
UM Sylvester Comprehensive Cancer Center at Aventura
RECRUITING
Aventura
Morton Plant Hospital
RECRUITING
Clearwater
UM Sylvester Comprehensive Cancer Center at Coral Gables
RECRUITING
Coral Gables
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
RECRUITING
Deerfield Beach
UM Sylvester Comprehensive Cancer Center at Kendall
RECRUITING
Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
RECRUITING
Miami
UM Sylvester Comprehensive Cancer Center at Plantation
RECRUITING
Plantation
Saint Joseph's Hospital/Children's Hospital-Tampa
RECRUITING
Tampa
Winter Haven Hospital
RECRUITING
Winter Haven
Georgia
CTCA at Southeastern Regional Medical Center
RECRUITING
Newnan
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
RECRUITING
Savannah
Iowa
Mary Greeley Medical Center
RECRUITING
Ames
McFarland Clinic - Ames
RECRUITING
Ames
Mission Cancer and Blood - Ankeny
SUSPENDED
Ankeny
Mercy Cancer Center-West Lakes
RECRUITING
Clive
Mission Cancer and Blood - West Des Moines
SUSPENDED
Clive
Greater Regional Medical Center
RECRUITING
Creston
Mercy Medical Center - Des Moines
RECRUITING
Des Moines
Mission Cancer and Blood - Laurel
SUSPENDED
Des Moines
Mercy Medical Center-West Lakes
RECRUITING
West Des Moines
Idaho
Saint Luke's Cancer Institute - Boise
RECRUITING
Boise
Saint Luke's Cancer Institute - Fruitland
RECRUITING
Fruitland
Saint Luke's Cancer Institute - Meridian
RECRUITING
Meridian
Saint Luke's Cancer Institute - Nampa
RECRUITING
Nampa
Saint Luke's Cancer Institute - Twin Falls
RECRUITING
Twin Falls
Illinois
Northwestern University
RECRUITING
Chicago
University of Chicago Comprehensive Cancer Center
RECRUITING
Chicago
University of Illinois
RECRUITING
Chicago
Carle at The Riverfront
RECRUITING
Danville
Decatur Memorial Hospital
RECRUITING
Decatur
Northwestern Medicine Cancer Center Kishwaukee
RECRUITING
Dekalb
Carle Physician Group-Effingham
RECRUITING
Effingham
Crossroads Cancer Center
RECRUITING
Effingham
Northwestern Medicine Cancer Center Delnor
RECRUITING
Geneva
Northwestern Medicine Glenview Outpatient Center
RECRUITING
Glenview
Northwestern Medicine Grayslake Outpatient Center
RECRUITING
Grayslake
Ingalls Memorial Hospital
RECRUITING
Harvey
Northwestern Medicine Lake Forest Hospital
RECRUITING
Lake Forest
Carle Physician Group-Mattoon/Charleston
RECRUITING
Mattoon
UC Comprehensive Cancer Center at Silver Cross
RECRUITING
New Lenox
HSHS Saint Elizabeth's Hospital
RECRUITING
O'fallon
University of Chicago Medicine-Orland Park
RECRUITING
Orland Park
Southern Illinois University School of Medicine
RECRUITING
Springfield
Springfield Clinic
RECRUITING
Springfield
Springfield Memorial Hospital
RECRUITING
Springfield
Carle Cancer Center
RECRUITING
Urbana
Northwestern Medicine Cancer Center Warrenville
RECRUITING
Warrenville
Kentucky
Saint Joseph Hospital East
RECRUITING
Lexington
University of Kentucky/Markey Cancer Center
RECRUITING
Lexington
Maine
MaineHealth Cancer Care Center of York County
RECRUITING
Sanford
Maine Medical Center- Scarborough Campus
RECRUITING
Scarborough
Maine Medical Partners - South Portland
RECRUITING
South Portland
Michigan
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
RECRUITING
Ann Arbor
Trinity Health IHA Medical Group Hematology Oncology - Brighton
RECRUITING
Brighton
Trinity Health Medical Center - Brighton
RECRUITING
Brighton
Trinity Health IHA Medical Group Hematology Oncology - Canton
RECRUITING
Canton
Trinity Health Medical Center - Canton
RECRUITING
Canton
Chelsea Hospital
RECRUITING
Chelsea
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
RECRUITING
Chelsea
Genesys Hurley Cancer Institute
RECRUITING
Flint
Hurley Medical Center
RECRUITING
Flint
Bronson Methodist Hospital
RECRUITING
Kalamazoo
West Michigan Cancer Center
RECRUITING
Kalamazoo
University of Michigan Health - Sparrow Lansing
RECRUITING
Lansing
Trinity Health Saint Mary Mercy Livonia Hospital
RECRUITING
Livonia
Michigan Healthcare Professionals Pontiac
RECRUITING
Pontiac
Trinity Health Saint Joseph Mercy Oakland Hospital
RECRUITING
Pontiac
MyMichigan Medical Center Saginaw
RECRUITING
Saginaw
Oncology Hematology Associates of Saginaw Valley PC
RECRUITING
Saginaw
MyMichigan Medical Center Tawas
RECRUITING
Tawas City
Saint Mary's Oncology/Hematology Associates of West Branch
SUSPENDED
West Branch
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
RECRUITING
Ypsilanti
Minnesota
Miller-Dwan Hospital
RECRUITING
Duluth
Hennepin County Medical Center
RECRUITING
Minneapolis
North Memorial Medical Health Center
RECRUITING
Robbinsdale
Mayo Clinic in Rochester
WITHDRAWN
Rochester
Regions Hospital
RECRUITING
Saint Paul
Missouri
Saint Francis Medical Center
RECRUITING
Cape Girardeau
Parkland Health Center - Farmington
RECRUITING
Farmington
Delbert Day Cancer Institute at PCRMC
RECRUITING
Rolla
Missouri Baptist Medical Center
RECRUITING
Saint Louis
Sainte Genevieve County Memorial Hospital
RECRUITING
Sainte Genevieve
Missouri Baptist Sullivan Hospital
RECRUITING
Sullivan
BJC Outpatient Center at Sunset Hills
RECRUITING
Sunset Hills
Montana
Bozeman Health Deaconess Hospital
RECRUITING
Bozeman
North Carolina
Duke University Medical Center
ACTIVE_NOT_RECRUITING
Durham
Duke Raleigh Hospital
RECRUITING
Raleigh
Wake Forest University Health Sciences
RECRUITING
Winston-salem
New York
Roswell Park Cancer Institute
ACTIVE_NOT_RECRUITING
Buffalo
Northwell Health/Center for Advanced Medicine
RECRUITING
Lake Success
Lenox Hill Hospital
RECRUITING
New York
Manhattan Eye Ear and Throat Hospital
RECRUITING
New York
Mount Sinai Chelsea
RECRUITING
New York
Mount Sinai Hospital
RECRUITING
New York
Mount Sinai West
RECRUITING
New York
Upstate Cancer Center at Oswego
RECRUITING
Oswego
State University of New York Upstate Medical University
RECRUITING
Syracuse
SUNY Upstate Medical Center-Community Campus
RECRUITING
Syracuse
Upstate Cancer Center at Verona
RECRUITING
Verona
Ohio
Summa Health System - Akron Campus
RECRUITING
Akron
Oklahoma
Cancer Centers of Southwest Oklahoma Research
RECRUITING
Lawton
Mercy Hospital Oklahoma City
RECRUITING
Oklahoma City
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Pennsylvania
Christiana Care Health System-Concord Health Center
RECRUITING
Chadds Ford
Geisinger Medical Center
RECRUITING
Danville
Penn State Milton S Hershey Medical Center
RECRUITING
Hershey
Geisinger Medical Oncology-Lewisburg
RECRUITING
Lewisburg
Penn State Health Saint Joseph Medical Center
RECRUITING
Reading
Geisinger Wyoming Valley/Henry Cancer Center
RECRUITING
Wilkes-barre
South Carolina
Medical University of South Carolina
RECRUITING
Charleston
Texas
The Don and Sybil Harrington Cancer Center
RECRUITING
Amarillo
Virginia
VCU Massey Cancer Center at Stony Point
RECRUITING
Richmond
Virginia Commonwealth University/Massey Cancer Center
RECRUITING
Richmond
Wisconsin
Northwest Wisconsin Cancer Center
RECRUITING
Ashland
Marshfield Medical Center-EC Cancer Center
RECRUITING
Eau Claire
Gundersen Lutheran Medical Center
RECRUITING
La Crosse
Mayo Clinic Health System-Franciscan Healthcare
ACTIVE_NOT_RECRUITING
La Crosse
Marshfield Medical Center-Marshfield
RECRUITING
Marshfield
Marshfield Medical Center - Minocqua
RECRUITING
Minocqua
ProHealth D N Greenwald Center
RECRUITING
Mukwonago
Cancer Center of Western Wisconsin
RECRUITING
New Richmond
ProHealth Oconomowoc Memorial Hospital
RECRUITING
Oconomowoc
Marshfield Medical Center-Rice Lake
RECRUITING
Rice Lake
Marshfield Medical Center-River Region at Stevens Point
RECRUITING
Stevens Point
UW Cancer Center at ProHealth Care
RECRUITING
Waukesha
Marshfield Medical Center - Weston
RECRUITING
Weston
West Virginia
West Virginia University Charleston Division
RECRUITING
Charleston
Time Frame
Start Date: 2022-10-07
Estimated Completion Date: 2027-12-31
Participants
Target number of participants: 427
Treatments
Experimental: Arm A (immunotherapy, +/- chemotherapy)
Patients receive nivolumab intravenously (IV) over 30 minutes on days 1 and 22 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity or patients may receive standard of care systemic immunotherapy. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening.
Experimental: Arm B (immunotherapy, +/- chemotherapy, radiation therapy)
Patients receive 1 of 6 treatment options as in Arm A. Patients also undergo 3 fractions of radiation therapy every other day. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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