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NCT04929041Active, not recruitingPhase 2/3

Testing the Addition of Radiation Therapy to the Usual Treatment (Immunotherapy With or Without Chemotherapy) for Advanced Stage Non-small Cell Lung Cancer Patients Who Are PD-L1 Negative

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

Source: ClinicalTrials.gov · Last updated 1 Oct 2026

Brief summary (registry, in English)

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.

Status (registry)
Active, not recruiting
Phase (registry)
Phase 2/3
Study type
Interventional
Enrollment
427 (estimated)
First submitted
16 Jun 2021
Start date
7 Oct 2022
Primary completion date
12 Dec 2030
Lead sponsor
National Cancer Institute (NCI)
Diseases
Lung cancer
NCT number
NCT04929041

What you commit to

  • Study type: Interventional · Phase 2/3
  • Planned participants: 427
  • From 7 Oct 2022 to the primary completion date, 12 Dec 2030
  • 169 sites in 1 country
  • Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Who the study is looking for

  • 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)

Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (169)

Sites in registry order. Pick your city on the disease page to sort them by distance.

SiteCityCountrySite status
Summa Health System - Akron Campus
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AkronUnited StatesUnknown status
The Don and Sybil Harrington Cancer Center
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AmarilloUnited StatesUnknown status
McFarland Clinic - Ames
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AmesUnited StatesUnknown status
Mary Greeley Medical Center
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AmesUnited StatesUnknown status
UI Health Care Mission Cancer and Blood - Ankeny Clinic
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AnkenyUnited StatesUnknown status
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Ann ArborUnited StatesUnknown status
Northwest Wisconsin Cancer Center
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AshlandUnited StatesUnknown status
UM Sylvester Comprehensive Cancer Center at Aventura
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AventuraUnited StatesUnknown status
Alta Bates Summit Medical Center-Herrick Campus
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BerkeleyUnited StatesUnknown status
Saint Luke's Cancer Institute - Boise
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BoiseUnited StatesUnknown status
Bozeman Health Deaconess Hospital
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BozemanUnited StatesUnknown status
Trinity Health Medical Center - Brighton
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BrightonUnited StatesUnknown status
Trinity Health IHA Medical Group Hematology Oncology - Brighton
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BrightonUnited StatesUnknown status
Roswell Park Cancer Institute
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BuffaloUnited StatesUnknown status
Trinity Health Medical Center - Canton
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CantonUnited StatesUnknown status
Trinity Health IHA Medical Group Hematology Oncology - Canton
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CantonUnited StatesUnknown status
Saint Francis Medical Center
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Cape GirardeauUnited StatesUnknown status
Christiana Care Health System-Concord Health Center
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Chadds FordUnited StatesUnknown status
Medical University of South Carolina
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CharlestonUnited StatesUnknown status
Vandalia Health/CAMC Institute for Academic Medicine
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CharlestonUnited StatesUnknown status
Chelsea Hospital
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ChelseaUnited StatesUnknown status
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
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ChelseaUnited StatesUnknown status
Northwestern University
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ChicagoUnited StatesUnknown status
University of Illinois
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ChicagoUnited StatesUnknown status
University of Chicago Comprehensive Cancer Center
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ChicagoUnited StatesUnknown status
Morton Plant Hospital
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ClearwaterUnited StatesUnknown status
Mercy Cancer Center-West Lakes
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CliveUnited StatesUnknown status
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
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CliveUnited StatesUnknown status
Memorial Hospital North
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Colorado SpringsUnited StatesUnknown status
UCHealth Memorial Hospital Central
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Colorado SpringsUnited StatesUnknown status
UM Sylvester Comprehensive Cancer Center at Coral Gables
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Coral GablesUnited StatesUnknown status
Greater Regional Medical Center
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CrestonUnited StatesUnknown status
UChicago Medicine Northwest Indiana
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Crown PointUnited StatesUnknown status
Carle at The Riverfront
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DanvilleUnited StatesUnknown status
Geisinger Medical Center
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DanvilleUnited StatesUnknown status
Decatur Memorial Hospital
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DecaturUnited StatesUnknown status
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
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Deerfield BeachUnited StatesUnknown status
Northwestern Medicine Cancer Center Kishwaukee
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DeKalbUnited StatesUnknown status
UI Health Care Mission Cancer and Blood - Laurel Clinic
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Des MoinesUnited StatesUnknown status
Mercy Medical Center - Des Moines
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Des MoinesUnited StatesUnknown status
UI Health Care Mission Cancer and Blood - Des Moines Clinic
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Des MoinesUnited StatesUnknown status
Iowa Methodist Medical Center
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Des MoinesUnited StatesUnknown status
City of Hope Comprehensive Cancer Center
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DuarteUnited StatesUnknown status
Miller-Dwan Hospital
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DuluthUnited StatesUnknown status
Duke University Medical Center
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DurhamUnited StatesUnknown status
Marshfield Medical Center-EC Cancer Center
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Eau ClaireUnited StatesUnknown status
Crossroads Cancer Center
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EffinghamUnited StatesUnknown status
Carle Physician Group-Effingham
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EffinghamUnited StatesUnknown status
Parkland Health Center - Farmington
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FarmingtonUnited StatesUnknown status
Hurley Medical Center
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FlintUnited StatesUnknown status
Genesys Hurley Cancer Institute
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FlintUnited StatesUnknown status
Cancer Care and Hematology-Fort Collins
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Fort CollinsUnited StatesUnknown status
Poudre Valley Hospital
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Fort CollinsUnited StatesUnknown status
Saint Luke's Cancer Institute - Fruitland
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FruitlandUnited StatesUnknown status
Northwestern Medicine Cancer Center Delnor
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GenevaUnited StatesUnknown status
Northwestern Medicine Glenview Outpatient Center
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GlenviewUnited StatesUnknown status
Northwestern Medicine Grayslake Outpatient Center
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GrayslakeUnited StatesUnknown status
UCHealth Greeley Hospital
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GreeleyUnited StatesUnknown status
Legacy Mount Hood Medical Center
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GreshamUnited StatesUnknown status
Ingalls Memorial Hospital
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HarveyUnited StatesUnknown status
Penn State Milton S. Hershey Medical Center
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HersheyUnited StatesUnknown status
City of Hope at Irvine Lennar
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IrvineUnited StatesUnknown status
Bronson Methodist Hospital
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KalamazooUnited StatesUnknown status
West Michigan Cancer Center
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KalamazooUnited StatesUnknown status
Mayo Clinic Health System-Franciscan Healthcare
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La CrosseUnited StatesUnknown status
Gundersen Lutheran Medical Center
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La CrosseUnited StatesUnknown status
Northwestern Medicine Lake Forest Hospital
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Lake ForestUnited StatesUnknown status
Northwell Health/Center for Advanced Medicine
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Lake SuccessUnited StatesUnknown status
City of Hope Antelope Valley
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LancasterUnited StatesUnknown status
University of Michigan Health - Sparrow Lansing
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LansingUnited StatesUnknown status
Cancer Centers of Southwest Oklahoma Research
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LawtonUnited StatesUnknown status
Geisinger Medical Oncology-Lewisburg
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LewisburgUnited StatesUnknown status
University of Kentucky/Markey Cancer Center
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LexingtonUnited StatesUnknown status
CommonSpirit Saint Joseph Medical Center - East Lexington
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LexingtonUnited StatesUnknown status
University of Arkansas for Medical Sciences
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Little RockUnited StatesUnknown status
Trinity Health Saint Mary Mercy Livonia Hospital
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LivoniaUnited StatesUnknown status
Medical Center of the Rockies
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LovelandUnited StatesUnknown status
Marshfield Medical Center-Marshfield
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MarshfieldUnited StatesUnknown status
Fremont - Rideout Cancer Center
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MarysvilleUnited StatesUnknown status
Carle Physician Group-Mattoon/Charleston
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MattoonUnited StatesUnknown status
Saint Luke's Cancer Institute - Meridian
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MeridianUnited StatesUnknown status
University of Miami Miller School of Medicine-Sylvester Cancer Center
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MiamiUnited StatesUnknown status
UM Sylvester Comprehensive Cancer Center at Kendall
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MiamiUnited StatesUnknown status
Beebe South Coastal Health Campus
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MillvilleUnited StatesUnknown status
Hennepin County Medical Center
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MinneapolisUnited StatesUnknown status
Marshfield Medical Center - Minocqua
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MinocquaUnited StatesUnknown status
Memorial Medical Center
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ModestoUnited StatesUnknown status
ProHealth D N Greenwald Center
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MukwonagoUnited StatesUnknown status
Saint Luke's Cancer Institute - Nampa
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NampaUnited StatesUnknown status
Providence Queen of The Valley
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NapaUnited StatesUnknown status
Helen F Graham Cancer Center
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NewarkUnited StatesUnknown status
Medical Oncology Hematology Consultants PA
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NewarkUnited StatesUnknown status
UC Comprehensive Cancer Center at Silver Cross
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New LenoxUnited StatesUnknown status
CTCA at Southeastern Regional Medical Center
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NewnanUnited StatesUnknown status
Cancer Center of Western Wisconsin
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New RichmondUnited StatesUnknown status
Lenox Hill Hospital
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New YorkUnited StatesUnknown status
Mount Sinai Chelsea
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New YorkUnited StatesUnknown status
Mount Sinai West
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New YorkUnited StatesUnknown status
Manhattan Eye Ear and Throat Hospital
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New YorkUnited StatesUnknown status
Mount Sinai Hospital
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New YorkUnited StatesUnknown status
ProHealth Oconomowoc Memorial Hospital
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OconomowocUnited StatesUnknown status
HSHS Saint Elizabeth's Hospital
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O'FallonUnited StatesUnknown status
Mercy Hospital Oklahoma City
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Oklahoma CityUnited StatesUnknown status
University of Oklahoma Health Sciences Center
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Oklahoma CityUnited StatesUnknown status
University of Chicago Medicine-Orland Park
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Orland ParkUnited StatesUnknown status
Upstate Cancer Center at Oswego
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OswegoUnited StatesUnknown status
Upstate Cancer Center Radiation Oncology at Oswego
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OswegoUnited StatesUnknown status
Mayo Clinic Hospital in Arizona
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PhoenixUnited StatesUnknown status
UM Sylvester Comprehensive Cancer Center at Plantation
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PlantationUnited StatesUnknown status
Michigan Healthcare Professionals Pontiac
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PontiacUnited StatesUnknown status
Trinity Health Saint Joseph Mercy Oakland Hospital
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PontiacUnited StatesUnknown status
Legacy Good Samaritan Hospital and Medical Center
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PortlandUnited StatesUnknown status
Oregon Health and Science University
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PortlandUnited StatesUnknown status
Duke Cancer Center Raleigh
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RaleighUnited StatesUnknown status
Penn State Health Saint Joseph Medical Center
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ReadingUnited StatesUnknown status
Beebe Health Campus
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Rehoboth BeachUnited StatesUnknown status
Marshfield Medical Center-Rice Lake
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Rice LakeUnited StatesUnknown status
VCU Massey Cancer Center at Stony Point
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RichmondUnited StatesUnknown status
VCU Massey Comprehensive Cancer Center
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RichmondUnited StatesUnknown status
North Memorial Medical Health Center
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RobbinsdaleUnited StatesUnknown status
UW Health Carbone Cancer Center Rockford
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RockfordUnited StatesUnknown status
Phelps Health Delbert Day Cancer Institute
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RollaUnited StatesUnknown status
University of California Davis Comprehensive Cancer Center
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SacramentoUnited StatesUnknown status
Oncology Hematology Associates of Saginaw Valley PC
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SaginawUnited StatesUnknown status
MyMichigan Medical Center Saginaw
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SaginawUnited StatesUnknown status
Coborn Cancer Center at Saint Cloud Hospital
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Saint CloudUnited StatesUnknown status
Sainte Genevieve County Memorial Hospital
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Sainte GenevieveUnited StatesUnknown status
Regions Hospital
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Saint PaulUnited StatesUnknown status
MaineHealth Cancer Care Center of York County
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SanfordUnited StatesUnknown status
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
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SavannahUnited StatesUnknown status
MaineHealth Maine Medical Center- Scarborough
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ScarboroughUnited StatesUnknown status
City of Hope South Pasadena
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South PasadenaUnited StatesUnknown status
MaineHealth Cancer Care and IV Therapy - South Portland
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South PortlandUnited StatesUnknown status
Mercy Hospital Springfield
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SpringfieldUnited StatesUnknown status
Springfield Clinic
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SpringfieldUnited StatesUnknown status
Springfield Memorial Hospital
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SpringfieldUnited StatesUnknown status
Southern Illinois University School of Medicine
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SpringfieldUnited StatesUnknown status
Marshfield Medical Center-River Region at Stevens Point
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Stevens PointUnited StatesUnknown status
Mercy Hospital South
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St LouisUnited StatesUnknown status
Missouri Baptist Medical Center
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St LouisUnited StatesUnknown status
Mercy Hospital Saint Louis
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St LouisUnited StatesUnknown status
Missouri Baptist Sullivan Hospital
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SullivanUnited StatesUnknown status
Upstate Cancer Center at Hill Radiation Oncology
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SyracuseUnited StatesUnknown status
SUNY Upstate Medical Center-Community Campus
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SyracuseUnited StatesUnknown status
State University of New York Upstate Medical University
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SyracuseUnited StatesUnknown status
Saint Joseph's Hospital/Children's Hospital-Tampa
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TampaUnited StatesUnknown status
VCU Health Tappahannock Hospital
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TappahannockUnited StatesUnknown status
MyMichigan Medical Center Tawas
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Tawas CityUnited StatesUnknown status
Gene Upshaw Memorial Tahoe Forest Cancer Center
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TruckeeUnited StatesUnknown status
Legacy Meridian Park Hospital
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TualatinUnited StatesUnknown status
Saint Luke's Cancer Institute - Twin Falls
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Twin FallsUnited StatesUnknown status
City of Hope Upland
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UplandUnited StatesUnknown status
Carle Cancer Center
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UrbanaUnited StatesUnknown status
Legacy Salmon Creek Hospital
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VancouverUnited StatesUnknown status
Legacy Cancer Institute Medical Oncology and Day Treatment
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VancouverUnited StatesUnknown status
Upstate Cancer Center at Verona
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VeronaUnited StatesUnknown status
Providence Saint Mary Regional Cancer Center
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Walla WallaUnited StatesUnknown status
Northwestern Medicine Cancer Center Warrenville
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WarrenvilleUnited StatesUnknown status
MedStar Washington Hospital Center
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Washington D.C.United StatesUnknown status
UI Health Care Mission Cancer and Blood - Waukee Clinic
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WaukeeUnited StatesUnknown status
UW Cancer Center at ProHealth Care
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WaukeshaUnited StatesUnknown status
Saint Mary's Oncology/Hematology Associates of West Branch
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West BranchUnited StatesUnknown status
The Iowa Clinic PC
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West Des MoinesUnited StatesUnknown status
Mercy Medical Center-West Lakes
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West Des MoinesUnited StatesUnknown status
Marshfield Medical Center - Weston
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WestonUnited StatesUnknown status
Geisinger Wyoming Valley/Henry Cancer Center
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Wilkes-BarreUnited StatesUnknown status
Wake Forest University Health Sciences
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Winston-SalemUnited StatesUnknown status
Winter Haven Hospital
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Winter HavenUnited StatesUnknown status
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
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YpsilantiUnited StatesUnknown status

This page is information, not medical advice. Discuss any trial with your doctor.