Stage IV Lung Cancer AJCC v8 Clinical Trial
Official title:
A Randomized Phase II/III Trial of Modern Immunotherapy Based Systemic Therapy With or Without SBRT for PD-L1-Negative, Advanced Non-Small Cell Lung Cancer
Verified date | March 2024 |
Source | National Cancer Institute (NCI) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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. Stereotactic body radiation therapy (SBRT) is a type of radiation therapy that uses high energy x-rays to kill tumor cells and shrink tumors. This method uses special equipment to position a patient and precisely deliver radiation to tumors with fewer doses over a shorter period and may cause less damage to normal tissue than conventional radiation therapy. 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.
Status | Recruiting |
Enrollment | 427 |
Est. completion date | December 31, 2027 |
Est. primary completion date | December 31, 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - 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 SBRT - 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) |
Country | Name | City | State |
---|---|---|---|
United States | Summa Health System - Akron Campus | Akron | Ohio |
United States | The Don and Sybil Harrington Cancer Center | Amarillo | Texas |
United States | Mary Greeley Medical Center | Ames | Iowa |
United States | McFarland Clinic - Ames | Ames | Iowa |
United States | Trinity Health Saint Joseph Mercy Hospital Ann Arbor | Ann Arbor | Michigan |
United States | UM Sylvester Comprehensive Cancer Center at Aventura | Aventura | Florida |
United States | Alta Bates Summit Medical Center-Herrick Campus | Berkeley | California |
United States | Saint Luke's Cancer Institute - Boise | Boise | Idaho |
United States | Trinity Health IHA Medical Group Hematology Oncology - Brighton | Brighton | Michigan |
United States | Trinity Health Medical Center - Brighton | Brighton | Michigan |
United States | Roswell Park Cancer Institute | Buffalo | New York |
United States | Trinity Health IHA Medical Group Hematology Oncology - Canton | Canton | Michigan |
United States | Trinity Health Medical Center - Canton | Canton | Michigan |
United States | Saint Francis Medical Center | Cape Girardeau | Missouri |
United States | Christiana Care Health System-Concord Health Center | Chadds Ford | Pennsylvania |
United States | Medical University of South Carolina | Charleston | South Carolina |
United States | West Virginia University Charleston Division | Charleston | West Virginia |
United States | Chelsea Hospital | Chelsea | Michigan |
United States | Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital | Chelsea | Michigan |
United States | Northwestern University | Chicago | Illinois |
United States | University of Chicago Comprehensive Cancer Center | Chicago | Illinois |
United States | University of Illinois | Chicago | Illinois |
United States | Mercy Cancer Center-West Lakes | Clive | Iowa |
United States | Mission Cancer and Blood - West Des Moines | Clive | Iowa |
United States | Memorial Hospital North | Colorado Springs | Colorado |
United States | UCHealth Memorial Hospital Central | Colorado Springs | Colorado |
United States | UM Sylvester Comprehensive Cancer Center at Coral Gables | Coral Gables | Florida |
United States | Greater Regional Medical Center | Creston | Iowa |
United States | Carle at The Riverfront | Danville | Illinois |
United States | Geisinger Medical Center | Danville | Pennsylvania |
United States | Decatur Memorial Hospital | Decatur | Illinois |
United States | UM Sylvester Comprehensive Cancer Center at Deerfield Beach | Deerfield Beach | Florida |
United States | Northwestern Medicine Cancer Center Kishwaukee | DeKalb | Illinois |
United States | Mercy Medical Center - Des Moines | Des Moines | Iowa |
United States | Mission Cancer and Blood - Laurel | Des Moines | Iowa |
United States | City of Hope Comprehensive Cancer Center | Duarte | California |
United States | Duke University Medical Center | Durham | North Carolina |
United States | Marshfield Medical Center-EC Cancer Center | Eau Claire | Wisconsin |
United States | Carle Physician Group-Effingham | Effingham | Illinois |
United States | Crossroads Cancer Center | Effingham | Illinois |
United States | Parkland Health Center - Farmington | Farmington | Missouri |
United States | Genesys Hurley Cancer Institute | Flint | Michigan |
United States | Hurley Medical Center | Flint | Michigan |
United States | Cancer Care and Hematology-Fort Collins | Fort Collins | Colorado |
United States | Poudre Valley Hospital | Fort Collins | Colorado |
United States | Beebe South Coastal Health Campus | Frankford | Delaware |
United States | Saint Luke's Cancer Institute - Fruitland | Fruitland | Idaho |
United States | Northwestern Medicine Cancer Center Delnor | Geneva | Illinois |
United States | Northwestern Medicine Glenview Outpatient Center | Glenview | Illinois |
United States | Northwestern Medicine Grayslake Outpatient Center | Grayslake | Illinois |
United States | UCHealth Greeley Hospital | Greeley | Colorado |
United States | Ingalls Memorial Hospital | Harvey | Illinois |
United States | Penn State Milton S Hershey Medical Center | Hershey | Pennsylvania |
United States | City of Hope at Irvine Lennar | Irvine | California |
United States | Bronson Methodist Hospital | Kalamazoo | Michigan |
United States | West Michigan Cancer Center | Kalamazoo | Michigan |
United States | Gundersen Lutheran Medical Center | La Crosse | Wisconsin |
United States | Mayo Clinic Health System-Franciscan Healthcare | La Crosse | Wisconsin |
United States | Northwestern Medicine Lake Forest Hospital | Lake Forest | Illinois |
United States | Northwell Health/Center for Advanced Medicine | Lake Success | New York |
United States | City of Hope Antelope Valley | Lancaster | California |
United States | University of Michigan Health - Sparrow Lansing | Lansing | Michigan |
United States | Cancer Centers of Southwest Oklahoma Research | Lawton | Oklahoma |
United States | Geisinger Medical Oncology-Lewisburg | Lewisburg | Pennsylvania |
United States | Saint Joseph Hospital East | Lexington | Kentucky |
United States | University of Kentucky/Markey Cancer Center | Lexington | Kentucky |
United States | Trinity Health Saint Mary Mercy Livonia Hospital | Livonia | Michigan |
United States | Medical Center of the Rockies | Loveland | Colorado |
United States | Marshfield Medical Center-Marshfield | Marshfield | Wisconsin |
United States | Fremont - Rideout Cancer Center | Marysville | California |
United States | Carle Physician Group-Mattoon/Charleston | Mattoon | Illinois |
United States | Saint Luke's Cancer Institute - Meridian | Meridian | Idaho |
United States | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida |
United States | Hennepin County Medical Center | Minneapolis | Minnesota |
United States | Marshfield Clinic-Minocqua Center | Minocqua | Wisconsin |
United States | ProHealth D N Greenwald Center | Mukwonago | Wisconsin |
United States | Saint Luke's Cancer Institute - Nampa | Nampa | Idaho |
United States | Providence Queen of The Valley | Napa | California |
United States | UC Comprehensive Cancer Center at Silver Cross | New Lenox | Illinois |
United States | Lenox Hill Hospital | New York | New York |
United States | Manhattan Eye Ear and Throat Hospital | New York | New York |
United States | Mount Sinai Chelsea | New York | New York |
United States | Mount Sinai Hospital | New York | New York |
United States | Mount Sinai West | New York | New York |
United States | Helen F Graham Cancer Center | Newark | Delaware |
United States | Medical Oncology Hematology Consultants PA | Newark | Delaware |
United States | CTCA at Southeastern Regional Medical Center | Newnan | Georgia |
United States | ProHealth Oconomowoc Memorial Hospital | Oconomowoc | Wisconsin |
United States | Mercy Hospital Oklahoma City | Oklahoma City | Oklahoma |
United States | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma |
United States | University of Chicago Medicine-Orland Park | Orland Park | Illinois |
United States | Upstate Cancer Center at Oswego | Oswego | New York |
United States | Mayo Clinic Hospital in Arizona | Phoenix | Arizona |
United States | Michigan Healthcare Professionals Pontiac | Pontiac | Michigan |
United States | Trinity Health Saint Joseph Mercy Oakland Hospital | Pontiac | Michigan |
United States | Duke Raleigh Hospital | Raleigh | North Carolina |
United States | Beebe Health Campus | Rehoboth Beach | Delaware |
United States | Marshfield Medical Center-Rice Lake | Rice Lake | Wisconsin |
United States | VCU Massey Cancer Center at Stony Point | Richmond | Virginia |
United States | Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia |
United States | North Memorial Medical Health Center | Robbinsdale | Minnesota |
United States | Mayo Clinic in Rochester | Rochester | Minnesota |
United States | Delbert Day Cancer Institute at PCRMC | Rolla | Missouri |
United States | University of California Davis Comprehensive Cancer Center | Sacramento | California |
United States | Missouri Baptist Medical Center | Saint Louis | Missouri |
United States | Regions Hospital | Saint Paul | Minnesota |
United States | Sainte Genevieve County Memorial Hospital | Sainte Genevieve | Missouri |
United States | MaineHealth Cancer Care Center of York County | Sanford | Maine |
United States | Lewis Cancer and Research Pavilion at Saint Joseph's/Candler | Savannah | Georgia |
United States | Maine Medical Center- Scarborough Campus | Scarborough | Maine |
United States | City of Hope South Pasadena | South Pasadena | California |
United States | Maine Medical Partners - South Portland | South Portland | Maine |
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 | Marshfield Medical Center-River Region at Stevens Point | Stevens Point | Wisconsin |
United States | Missouri Baptist Sullivan Hospital | Sullivan | Missouri |
United States | BJC Outpatient Center at Sunset Hills | Sunset Hills | Missouri |
United States | State University of New York Upstate Medical University | Syracuse | New York |
United States | SUNY Upstate Medical Center-Community Campus | Syracuse | New York |
United States | Gene Upshaw Memorial Tahoe Forest Cancer Center | Truckee | California |
United States | Saint Luke's Cancer Institute - Twin Falls | Twin Falls | Idaho |
United States | City of Hope Upland | Upland | California |
United States | Carle Cancer Center | Urbana | Illinois |
United States | Upstate Cancer Center at Verona | Verona | New York |
United States | Northwestern Medicine Cancer Center Warrenville | Warrenville | Illinois |
United States | MedStar Washington Hospital Center | Washington | District of Columbia |
United States | UW Cancer Center at ProHealth Care | Waukesha | Wisconsin |
United States | Mercy Medical Center-West Lakes | West Des Moines | Iowa |
United States | Marshfield Medical Center - Weston | Weston | Wisconsin |
United States | Geisinger Wyoming Valley/Henry Cancer Center | Wilkes-Barre | Pennsylvania |
United States | Wake Forest University Health Sciences | Winston-Salem | North Carolina |
United States | Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus | Ypsilanti | Michigan |
Lead Sponsor | Collaborator |
---|---|
National Cancer Institute (NCI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Progression-free survival (PFS) (Phase II) | Will be performed on an intent-to-treat (ITT) basis. | From randomization to disease progression or death of all causes, whichever comes first, assessed up to 5 years | |
Primary | Overall survival (OS) (Phase III) | Will be performed on an ITT basis. The comparison of the distributions of OS between treatment arms will be done with a one-sided stratified log-rank test). The rates at various time points (e.g., every 6 months after randomization) and medians of OS for each arm will be estimated using the Kaplan-Meier estimator. The associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Hazard ratios will be estimated using a stratified Cox regression model. The final phase III analysis of OS will be considered as "positive" if the stratified log-rank test statistics Z-value greater than the critical value adjusted for type 1 error using group sequential methods. Multivariable Cox models will be used to evaluate the treatment effect on survival time and its interaction with baseline covariates, including stage, systemic therapy, histology and performance status. | From randomization and death of all causes, assessed up to 5 years | |
Secondary | PFS | Assessed per Response Evaluation Criteria in Solid Tumors (RECIST). | From randomization to disease progression or death of all causes, whichever comes first, assessed up to 5 years | |
Secondary | Objective response rate (ORR) | Assessed per RECIST for both irradiated and un-irradiated areas. The ORRs between treatments will be compared with Fisher's exact test. The difference of ORR between treatments will be estimated by the Miettinen-Nurminen method and its 95% CI will be given. Multivariable logistic regression will be used to evaluate the treatment effect on ORR while adjusting for significant baseline covariates. | Up to 5 years | |
Secondary | Quality of life | Up to 5 years | ||
Secondary | Incidence of treatment-related adverse events | Treatment-related toxicity will be summarized by grade, type, and system organ class. Comparisons of the percentages of patients experiencing an adverse event between Arm A and Arm B will be performed using Fisher's exact test. | Up to 5 years |
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