Pemetrexed Disodium or Erlotinib Hydrochloride as Second-Line Therapy in Treating Patients With Advanced Non-small Cell Lung Cancer

Phase 3

Terminated

Conditions: Stage IIIA Non-Small Cell Lung Cancer
Stage IV Non-Small Cell Lung Cancer
Recurrent Non-Small Cell Lung Carcinoma
Stage IIIB Non-Small Cell Lung Cancer

Interventions: Drug: Pemetrexed Disodium
Drug: Erlotinib Hydrochloride

Registration Number: NCT00738881

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This randomized phase III trial studies pemetrexed disodium to see how well it works compared with erlotinib hydrochloride as second-line therapy in treating patients with non-small cell lung cancer that has spread to other places in the body. Pemetrexed disodium and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether pemetrexed disodium is more effective than erlotinib hydrochloride in treating advanced non-small cell lung cancer.

Detailed Description: PRIMARY OBJECTIVES:

I. To evaluate whether there are differences in progression-free survival due to treatment with erlotinib (erlotinib hydrochloride) compared to pemetrexed (pemetrexed disodium) for subsets of previously treated non-small cell lung cancer (NSCLC) patients defined by epidermal growth factor receptor (EGFR)-fluorescent in situ hybridization (FISH) positive versus negativity.

SECONDARY OBJECTIVES:

I. Ascertain the presence or absence of true differences due to treatment in the objective clinical endpoints of overall survival, confirmed response rate, and adverse event profile for subsets of patients defined on the basis of the epidermal growth factor receptor (EGFR)-FISH positivity versus negativity.

II. Ascertain the presence or absence of true differences due to treatment in objective clinical endpoints (i.e., progression free survival, overall survival, confirmed response rate, and adverse event profile) for subsets of patients defined on the basis of the epidermal growth factor receptor (EGFR) expression as measured by immunohistochemistry (IHC).

III. Ascertain the presence or absence of true differences due to treatment in objective clinical endpoints (i.e., progression free survival, overall survival, confirmed response rate, and adverse event profile) for subsets of patients defined on the basis of the epidermal growth factor receptor (EGFR) gene mutation status (MUT).

IV. To evaluate the prognostic effect of EGFR copy number as measured by FISH separately by treatment arm, i.e., is there a difference in outcome for FISH(+) patients receiving erlotinib compared to FISH (-) patients receiving erlotinib, and similarly is there a difference in outcome for FISH(+) patients receiving pemetrexed compared to FISH (-) patients receiving pemetrexed.

V. To evaluate the prognostic effect of EGFR expression as measured by IHC separately by treatment arm, i.e., is there a difference in outcome for IHC(+) patients receiving erlotinib compared to IHC (-) patients receiving erlotinib, and similarly is there a difference in outcome for IHC(+) patients receiving pemetrexed compared to IHC (-)patients receiving pemetrexed.

VI. To evaluate the prognostic effect of EGFR mutation status separately by treatment arm, i.e., is there a difference in outcome for MUT(+) patients receiving erlotinib compared to MUT(-) patients receiving erlotinib, and similarly is there a difference in outcome for MUT(+) patients receiving pemetrexed compared to MUT(-) patients receiving pemetrexed.

VII. To prospectively test the hypothesis that functionally relevant polymorphisms in the genes encoding for pemetrexed targets, as well as genes encoding for one or more of the key enzymes involved in the transport, activation, and inactivation of pemetrexed, either singly or in combination, play a role in the efficacy and/or toxicity of pemetrexed.

VIII. To prospectively test the hypothesis that functionally relevant polymorphisms in the EGFR gene as well as genes encoding for one or more of the key enzymes involved in the metabolism of erlotinib, either singly or in combination, play a role in the efficacy and/or toxicity of erlotinib.

IX. Evaluate proteomic signatures in blood samples as predictors of survival and response to treatment with erlotinib.

X. To evaluate expression of thymidylate synthase, dihydrofolate reductase, phosphoribosylglycineamide (GAR) formyltransferase, and methylthioadenosine phosphorylase gene expression in tumor samples, as measured by IHC or quantitative polymerase chain reaction, as predictors of survival and response to treatment with pemetrexed.

XI. To evaluate proteomic signatures in blood samples of patients as predictors of response and survival to treatment with erlotinib.

XII. To evaluate the following variables measured in tumor samples, as predictors of response and survival to treatment with pemetrexed: Expression of thymidylate synthase, dihydrofolate reductase and GAR formyltransferase genes methylthioadenosine phosphorylase expression by IHC or quantitative polymerase chain reaction (PCR).

XIII. To evaluate the following variables measured in tumor samples, as predictors of response and survival to treatment with erlotinib: Rat sarcoma (Ras) mutational status, EGFR mutational status and, epithelial to mesenchymal transition (EMT) status (measured by E-cadherin expression and vimentin expression) by IHC.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive pemetrexed disodium intravenously (IV) over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 23

Inclusion Criteria

Documented recurrence or disease progression of NSCLC
- NSCLC must be confirmed by pathologic examination, either on initial diagnosis or disease recurrence/progression; mixed histology allowed if all components consistent with NSCLC
Measurable disease, defined as at least one lesion whose longest diameter can be accurately measured as >= 2.0 cm by conventional techniques or as >= 1.0 cm by spiral computed tomography (CT); if spiral CT is used, it must be used for both pre- and post- treatment tumor assessments
Prior radiation therapy is permitted as long as:
- Recovered from the toxic effects of radiation treatment before study entry, except for alopecia
- =< 25% of bone marrow radiated
- Presence of measurable disease whether in-field disease progression/recurrence or disease outside the treatment fields of radiation port
Absolute neutrophil count (ANC) >= 1,500 uL
Platelet (PLT) >= 100,000 uL
Hemoglobin (Hgb) >= 10 g/dL
Total bilirubin: within normal institutional limits (WNL) OR direct bilirubin =< upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
International normalized ratio (INR) =< 1.5
Calculated creatinine clearance >= 45 mL/min using the Cockcroft-Gault formula
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
Negative pregnancy test done =< 7 days prior to pre-registration, for women of childbearing potential only
Ability to provide informed consent
Life expectancy >= 12 weeks
Tissue available and willing to submit tissue for central pathology review and EGFR evaluation; performed on original diagnostic/recurrent tissue (preferably paraffin-embedded tissue blocks); if institution unable to release tissue blocks, willing to submit 25 unstained slides (15 sections cut at 5 microns mounted on charged slides and 10 sections cut at 10 microns mounted on uncharged slides)
Must be previously treated for advanced disease with only 1 chemotherapy regimen which must contain cytotoxic agent(s); adjuvant/neoadjuvant treatment with cytotoxic agent(s) administered < 12 months (from date chemotherapy was started) prior to pre-registration will be considered as one prior treatment; NOTE: adjuvant/neoadjuvant treatment administered >= 12 months, use of targeted agents such as monoclonal antibodies prior to pre-registration will NOT be counted as one prior treatment; patient could have had adjuvant/neoadjuvant chemotherapy >= 12 months and 1 systemic chemotherapy regimen for metastatic or recurrent disease
Able to take folic acid, vitamin B12 supplementation, and dexamethasone
Able to permanently discontinue aspirin dose of >= 1.3 grams/day >= 10 days before and after pemetrexed treatment
Fertile patients must use effective contraception
Able to take folic acid, vitamin B_12 supplementation, and dexamethasone
Stable brain metastasis that have been treated with either whole brain radiation therapy or gamma knife surgery and are off steroid treatment for > 14 days prior to pre-registration, if applicable
Willingness to return to enrolling institution for treatment and follow-up

Exclusion Criteria

Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
Any clinically significant infection, at the treating physician's discretion
Known human immunodeficiency virus (HIV) positive patients
Impairment of gastrointestinal (GI) function, inability to swallow pills in the absence of a feeding tube, or GI disease that may significantly alter absorption of oral medications (e.g. ulcerative disease, uncontrolled nausea and vomiting, malabsorption syndromes, bowel obstruction, etc)
Serious condition that, in the opinion of the investigator, would compromise the patient's ability to complete the study or increase the risk for serious adverse events
Any of the following prior therapies:
- Prior radiation to > 25% of bone marrow
- EGFR tyrosine kinase inhibitors
- Pemetrexed
- Chemotherapy =< 3 weeks prior to pre-registration
- Mitomycin C/nitrosoureas =< 6 weeks prior to pre-registration
- Immunotherapy =< 2 weeks prior to pre-registration
- Biologic therapy =< 2 weeks prior to pre-registration
- Gene therapy =< 2 weeks prior to pre-registration
- Full field radiation therapy =< 4 weeks prior to pre-registration
- Limited field radiation therapy =< 2 weeks prior to pre-registration
- Major surgery (i.e., laparotomy), open biopsy, or significant traumatic injury =< 4 weeks prior to pre-registration or anticipation of need for major surgical procedure during the course of the study; minor surgery =< 2 weeks prior to pre-registration; insertion of a vascular access device is not considered major or minor surgery in this regard
Other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) =< 4 weeks prior to pre-registration
Steroid therapy for brain metastasis =< 14 days prior to pre-registration
Symptomatic serosal effusion (>= Common Terminology Criteria for Adverse Events [CTCAE] v3.0 grade 2 dyspnea) that is not amenable to drainage prior to pre-registration
Other invasive solid or hematologic malignancy; exceptions: prior malignancy was diagnosed and definitively treated >= 5 years previously with no subsequent evidence of recurrence; patients with a history of low-grade (Gleason score =< 6) localized prostate cancer will be eligible even if diagnosed < 3 years prior to pre-registration; these patients may continue on medications concomitantly to maintain their disease remission as necessary; patients with carcinoma in situ, regardless of organ involvement, or non-melanoma cutaneous carcinomas are eligible if these were definitively treated >= 3 years previously with no subsequent evidence of recurrence; Note: patients with breast cancer that was definitively treated > 5 years earlier but continue to receive aromatase inhibitors are NOT eligible
Only non-measurable disease, defined as all other lesions, including small lesions whose longest diameter measures < 2 cm with conventional techniques or < 1.0 cm with spiral CT, and truly non-measurable lesions, which include the following as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria dated June 1999:
- Bone lesions
- Leptomeningeal disease
- Ascites
- Pleural/pericardial effusion
- Inflammatory breast disease
- Lymphangitis cutis/pulmonis
- Abdominal masses that are not confirmed and followed by imaging techniques
- Cystic lesions
- Single disease site in prior radiation field
Any of the following concurrent severe and/or uncontrolled medical conditions:
- Angina pectoris
- History of congestive heart failure =< 3 months prior to pre-registration, unless ejection fraction > 40%
- Myocardial infarction =< 6 months prior to pre-registration
- Cardiac arrhythmia
- Diabetes mellitus
- Hypertension
- Any other severe underlying diseases which are, in the judgment of the investigator, inappropriate for entry into this study
Respiratory symptoms > CTCAE grade 1

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (pemetrexed disodium)	Pemetrexed Disodium	Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Arm I (erlotinib hydrochloride)	Erlotinib Hydrochloride	Patients receive erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	Time from randomization to the first date of documented disease progression or death, assessed up to 5 years	Estimated using the method of Kaplan-Meier survival curves to compare PFS between the erlotinib and pemetrexed arms using an intent-to-treat (ITT) analysis. Due to the small sample size (21 of the required 954 patients \~2%), analyses within the FISH(+) and FISH(-) groups were not performed, and no formal analyses for the primary or the secondary efficacy outcomes were performed.

Secondary Outcome Measures

Name	Time	Method
Time to Treatment Failure	The time from date of randomization to the date at which the patient is removed from the treatment, assessed up to 5 years	The distribution of all time to event data will be estimated using the method of Kaplan-Meier survival curves.
Overall Survival	Time from randomization to time of death from any cause, assessed up to 5 years	Will be estimated using the method of Kaplan-Meier survival curves. A 1-sided stratified log rank test \[accounting for all the stratification factors except FISH status and cooperative group\] will be used to compare overall survival between the erlotinib and pemetrexed arms within the FISH(+) and FISH(-) subgroups, compare overall and progression free survival between the erlotinib and pemetrexed arms within the subgroups defined on the basis of the epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC), and EGFR gene mutation status (MUT). Cox proportional hazards model will be used to assess potential differences.
Confirmed Response Rate Defined as Complete Response (CR) or a Partial Response (PR) Per Response Evaluation Criteria In Solid Tumors (RECIST)	Up to 5 years	Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. The proportion of patients with confirmed CR and PR will be computed within each treatment arm and exact binomial confidence intervals for the true proportion computed. Chi-square test and Fisher's exact test will be used to compare the response rates between the treatment arms within the subgroups defined by FISH status, IHC, and MUT.

Trial Locations

Locations (268): Lynn Regional Cancer Center - West
🇺🇸
Boca Raton, Florida, United States
Illinois CancerCare-Canton
🇺🇸
Canton, Illinois, United States
Illinois CancerCare-Carthage
🇺🇸
Carthage, Illinois, United States
Memorial Hospital
🇺🇸
Carthage, Illinois, United States
Eureka Hospital
🇺🇸
Eureka, Illinois, United States
Kalispell Regional Medical Center
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Kalispell, Montana, United States
Guardian Oncology and Center for Wellness
🇺🇸
Missoula, Montana, United States
Mount Nittany Medical Center
🇺🇸
State College, Pennsylvania, United States
Illinois CancerCare-Macomb
🇺🇸
Macomb, Illinois, United States
Glacier Oncology PLLC
🇺🇸
Kalispell, Montana, United States
Saint John Macomb-Oakland Hospital
🇺🇸
Warren, Michigan, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
Regions Hospital
🇺🇸
Saint Paul, Minnesota, United States
Community Medical Hospital
🇺🇸
Missoula, Montana, United States
Kalispell Medical Oncology
🇺🇸
Kalispell, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸
Missoula, Montana, United States
Toledo Clinic Cancer Centers-Maumee
🇺🇸
Maumee, Ohio, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Kaiser Permanente-Fremont
🇺🇸
Fremont, California, United States
Kaiser Permanente-Deer Valley Medical Center
🇺🇸
Antioch, California, United States
Valley Care Health System - Pleasanton
🇺🇸
Pleasanton, California, United States
Kaiser Permanente-Redwood City
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Redwood City, California, United States
Kaiser Permanente-South San Francisco
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South San Francisco, California, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸
Santa Clara, California, United States
Kaiser Permanente-Vallejo
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Vallejo, California, United States
Kaiser Permanente Medical Center-Vacaville
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Vacaville, California, United States
SCL Health Lutheran Medical Center
🇺🇸
Wheat Ridge, Colorado, United States
Longmont United Hospital
🇺🇸
Longmont, Colorado, United States
Saint Joseph Medical Center
🇺🇸
Bloomington, Illinois, United States
Hematology and Oncology Associates
🇺🇸
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Galesburg Cottage Hospital
🇺🇸
Galesburg, Illinois, United States
Mcdonough District Hospital
🇺🇸
Macomb, Illinois, United States
Holy Family Medical Center
🇺🇸
Monmouth, Illinois, United States
Community Cancer Center Foundation
🇺🇸
Normal, Illinois, United States
Illinois CancerCare-Community Cancer Center
🇺🇸
Normal, Illinois, United States
Illinois CancerCare-Monmouth
🇺🇸
Monmouth, Illinois, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸
Ottawa, Illinois, United States
Illinois Valley Hospital
🇺🇸
Peru, Illinois, United States
Illinois Oncology Research Association CCOP
🇺🇸
Peoria, Illinois, United States
Hematology Oncology Associates-Quad Cities
🇺🇸
Bettendorf, Iowa, United States
Hematology Oncology Associates of Illinois - Skokie
🇺🇸
Skokie, Illinois, United States
Memorial Medical Center
🇺🇸
Springfield, Illinois, United States
Saint Margaret's Hospital
🇺🇸
Spring Valley, Illinois, United States
Reid Hospital and Health Care Services
🇺🇸
Richmond, Indiana, United States
Cedar Rapids Oncology Association
🇺🇸
Cedar Rapids, Iowa, United States
Mercy Medical Center-Sioux City
🇺🇸
Sioux City, Iowa, United States
Greater Baltimore Medical Center
🇺🇸
Baltimore, Maryland, United States
Cancer Trials Support Unit
🇺🇸
Rockville, Maryland, United States
Hickman Cancer Center
🇺🇸
Adrian, Michigan, United States
Oakwood Hospital and Medical Center
🇺🇸
Dearborn, Michigan, United States
Spectrum Health at Butterworth Campus
🇺🇸
Grand Rapids, Michigan, United States
Mercy Health Saint Mary's
🇺🇸
Grand Rapids, Michigan, United States
Saint Mary Mercy Hospital
🇺🇸
Livonia, Michigan, United States
Sparrow Hospital
🇺🇸
Lansing, Michigan, United States
Mercy Memorial Hospital
🇺🇸
Monroe, Michigan, United States
Toledo Clinic Cancer Centers-Monroe
🇺🇸
Monroe, Michigan, United States
Mercy Health Mercy Campus
🇺🇸
Muskegon, Michigan, United States
Essentia Health Cancer Center
🇺🇸
Duluth, Minnesota, United States
Hutchinson Area Health Care
🇺🇸
Hutchinson, Minnesota, United States
Saint Vincent Healthcare
🇺🇸
Billings, Montana, United States
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
🇺🇸
Mount Holly, New Jersey, United States
Veterans Adminstration New Jersey Health Care System
🇺🇸
East Orange, New Jersey, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Sanford Bismarck Medical Center
🇺🇸
Bismarck, North Dakota, United States
Syracuse Veterans Administration Medical Center
🇺🇸
Syracuse, New York, United States
Toledo Clinic Cancer Centers-Bowling Green
🇺🇸
Bowling Green, Ohio, United States
North Coast Cancer Care-Clyde
🇺🇸
Clyde, Ohio, United States
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸
Franklin, Ohio, United States
Hematology Oncology Center Incorporated
🇺🇸
Elyria, Ohio, United States
Saint Vincent Mercy Medical Center
🇺🇸
Toledo, Ohio, United States
Flower Hospital
🇺🇸
Sylvania, Ohio, United States
The Toledo Hospital/Toledo Children's Hospital
🇺🇸
Toledo, Ohio, United States
Greene Memorial Hospital
🇺🇸
Xenia, Ohio, United States
Geisinger Medical Center-Cancer Center Hazleton
🇺🇸
Hazleton, Pennsylvania, United States
Geisinger Medical Group
🇺🇸
State College, Pennsylvania, United States
Fredericksburg Oncology Inc
🇺🇸
Fredericksburg, Virginia, United States
Kaiser Permanente-San Francisco
🇺🇸
San Francisco, California, United States
Kaiser Permanente San Leandro
🇺🇸
San Leandro, California, United States
Saint Luke's South Hospital
🇺🇸
Overland Park, Kansas, United States
Stormont-Vail Regional Health Center
🇺🇸
Topeka, Kansas, United States
Welch Cancer Center
🇺🇸
Sheridan, Wyoming, United States
Boston Medical Center
🇺🇸
Boston, Massachusetts, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Swedish Medical Center
🇺🇸
Englewood, Colorado, United States
Billings Clinic Cancer Center
🇺🇸
Billings, Montana, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸
Butte, Montana, United States
Montana Cancer Specialists
🇺🇸
Missoula, Montana, United States
Great Falls Clinic
🇺🇸
Great Falls, Montana, United States
Frontier Cancer Center and Blood Institute-Billings
🇺🇸
Billings, Montana, United States
Bozeman Deaconess Hospital
🇺🇸
Bozeman, Montana, United States
Berdeaux, Donald MD (UIA Investigator)
🇺🇸
Great Falls, Montana, United States
Northern Rockies Radiation Oncology Center
🇺🇸
Billings, Montana, United States
Dayton CCOP
🇺🇸
Dayton, Ohio, United States
Heartland Regional Medical Center
🇺🇸
Saint Joseph, Missouri, United States
Saint Luke's East - Lee's Summit
🇺🇸
Lee's Summit, Missouri, United States
Liberty Hospital
🇺🇸
Liberty, Missouri, United States
Liberty Radiation Oncology Center
🇺🇸
Liberty, Missouri, United States
Saint Louis University Hospital
🇺🇸
Saint Louis, Missouri, United States
Missouri Baptist Medical Center
🇺🇸
Saint Louis, Missouri, United States
Kaiser Permanente-Santa Rosa
🇺🇸
Santa Rosa, California, United States
Kaiser Permanente-Walnut Creek
🇺🇸
Walnut Creek, California, United States
Sparks Regional Medical Center
🇺🇸
Fort Smith, Arkansas, United States
Kaiser Permanente-Richmond
🇺🇸
Richmond, California, United States
Kaiser Permanente-Roseville
🇺🇸
Roseville, California, United States
Kaiser Permanente-Santa Teresa-San Jose
🇺🇸
San Jose, California, United States
Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Kaiser Permanente-Oakland
🇺🇸
Oakland, California, United States
Kaiser Permanente-San Rafael
🇺🇸
San Rafael, California, United States
Fremont - Rideout Cancer Center
🇺🇸
Marysville, California, United States
Saint Mary's Hospital and Regional Medical Center
🇺🇸
Grand Junction, Colorado, United States
Tahoe Forest Cancer Center
🇺🇸
Truckee, California, United States
Penrose-Saint Francis Healthcare
🇺🇸
Colorado Springs, Colorado, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Mayo Clinic in Florida
🇺🇸
Jacksonville, Florida, United States
Boca Raton Comprehensive Cancer Center
🇺🇸
Boca Raton, Florida, United States
Sky Ridge Medical Center
🇺🇸
Lone Tree, Colorado, United States
Middlesex Hospital
🇺🇸
Middletown, Connecticut, United States
McKee Medical Center
🇺🇸
Loveland, Colorado, United States
North Suburban Medical Center
🇺🇸
Thornton, Colorado, United States
Bristol Hospital
🇺🇸
Bristol, Connecticut, United States
MacNeal Hospital and Cancer Center
🇺🇸
Berwyn, Illinois, United States
Graham Hospital Association
🇺🇸
Canton, Illinois, United States
Illinois CancerCare-Bloomington
🇺🇸
Bloomington, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸
Eureka, Illinois, United States
Illinois CancerCare-Havana
🇺🇸
Havana, Illinois, United States
Midwest Center for Hematology Oncology
🇺🇸
Joliet, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸
Kewanee, Illinois, United States
Illinois CancerCare Galesburg
🇺🇸
Galesburg, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸
Peoria, Illinois, United States
Illinois CancerCare-Cottage
🇺🇸
Galesburg, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸
Princeton, Illinois, United States
NorthShore Hematology Oncology-Libertyville
🇺🇸
Libertyville, Illinois, United States
Illinois Cancer Specialists-Niles
🇺🇸
Niles, Illinois, United States
Hematology Oncology Associates of Illinois-Highland Park
🇺🇸
Highland Park, Illinois, United States
DuPage Medical Group-Ogden
🇺🇸
Naperville, Illinois, United States
Mason District Hospital
🇺🇸
Havana, Illinois, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Bromenn Regional Medical Center
🇺🇸
Normal, Illinois, United States
Perry Memorial Hospital
🇺🇸
Princeton, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸
Ottawa, Illinois, United States
Pekin Cancer Treatment Center
🇺🇸
Pekin, Illinois, United States
Proctor Hospital
🇺🇸
Peoria, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸
Pekin, Illinois, United States
Pekin Hospital
🇺🇸
Pekin, Illinois, United States
OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC
🇺🇸
Peoria, Illinois, United States
Illinois CancerCare-Peru
🇺🇸
Peru, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸
Peoria, Illinois, United States
Siouxland Regional Cancer Center
🇺🇸
Sioux City, Iowa, United States
Menorah Medical Center
🇺🇸
Overland Park, Kansas, United States
Illinois CancerCare-Spring Valley
🇺🇸
Spring Valley, Illinois, United States
Genesis Medical Center - East Campus
🇺🇸
Davenport, Iowa, United States
Bixby Medical Center
🇺🇸
Adrian, Michigan, United States
Spectrum Health Big Rapids Hospital
🇺🇸
Big Rapids, Michigan, United States
Shawnee Mission Medical Center-KCCC
🇺🇸
Shawnee Mission, Kansas, United States
Genesis Medical Center - West Campus
🇺🇸
Davenport, Iowa, United States
Oncology Associates at Mercy Medical Center
🇺🇸
Cedar Rapids, Iowa, United States
Medical Oncology and Hematology Associates-West Des Moines
🇺🇸
Clive, Iowa, United States
Franciscan St. Francis Health-Beech Grove
🇺🇸
Beech Grove, Indiana, United States
The Memorial Hospital at Easton
🇺🇸
Easton, Maryland, United States
Steward Saint Elizabeth's Medical Center
🇺🇸
Brighton, Massachusetts, United States
Bronson Battle Creek
🇺🇸
Battle Creek, Michigan, United States
Covenant Medical Center
🇺🇸
Waterloo, Iowa, United States
Cape Cod Hospital
🇺🇸
Hyannis, Massachusetts, United States
Saint Luke's Regional Medical Center
🇺🇸
Sioux City, Iowa, United States
Hospital District Sixth of Harper County
🇺🇸
Anthony, Kansas, United States
Genesys Regional Medical Center-West Flint Campus
🇺🇸
Flint, Michigan, United States
Saint Mary's of Michigan
🇺🇸
Saginaw, Michigan, United States
Miller-Dwan Hospital
🇺🇸
Duluth, Minnesota, United States
Minnesota Cooperative Group Outreach Program
🇺🇸
Minneapolis, Minnesota, United States
Munson Medical Center
🇺🇸
Traverse City, Michigan, United States
Essentia Health Saint Mary's Medical Center
🇺🇸
Duluth, Minnesota, United States
Meeker County Memorial Hospital
🇺🇸
Litchfield, Minnesota, United States
Virginia Piper Cancer Institute
🇺🇸
Minneapolis, Minnesota, United States
Metro Health Hospital
🇺🇸
Wyoming, Michigan, United States
Hennepin County Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸
Maplewood, Minnesota, United States
Rice Memorial Hospital
🇺🇸
Willmar, Minnesota, United States
CHI Health Good Samaritan
🇺🇸
Kearney, Nebraska, United States
North Coast Cancer Care
🇺🇸
Sandusky, Ohio, United States
Margaret R Pardee Memorial Hospital
🇺🇸
Hendersonville, North Carolina, United States
Montana Cancer Consortium NCORP
🇺🇸
Billings, Montana, United States
Bozeman Deaconess Cancer Center
🇺🇸
Bozeman, Montana, United States
Virtua West Jersey Hospital Voorhees
🇺🇸
Voorhees, New Jersey, United States
Northern Montana Hospital
🇺🇸
Havre, Montana, United States
Saint Peter's Community Hospital
🇺🇸
Helena, Montana, United States
Hunterdon Medical Center
🇺🇸
Flemington, New Jersey, United States
Samaritan North Health Center
🇺🇸
Dayton, Ohio, United States
Saint Alexius Medical Center
🇺🇸
Bismarck, North Dakota, United States
Rutherford Hospital
🇺🇸
Rutherfordton, North Carolina, United States
Saint Luke's Hospital
🇺🇸
Maumee, Ohio, United States
Mercy Saint Anne Hospital
🇺🇸
Toledo, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
Wayne Memorial Hospital
🇺🇸
Goldsboro, North Carolina, United States
Wayne Hospital
🇺🇸
Greenville, Ohio, United States
University of Toledo
🇺🇸
Toledo, Ohio, United States
Mercy Hospital of Tiffin
🇺🇸
Tiffin, Ohio, United States
Kettering Medical Center
🇺🇸
Kettering, Ohio, United States
Toledo Clinic Cancer Centers-Toledo
🇺🇸
Toledo, Ohio, United States
Blanchard Valley Hospital
🇺🇸
Findlay, Ohio, United States
Lima Memorial Hospital
🇺🇸
Lima, Ohio, United States
Toledo Community Hospital Oncology Program CCOP
🇺🇸
Toledo, Ohio, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Toledo Clinic Cancer Centers-Oregon
🇺🇸
Oregon, Ohio, United States
Fulton County Health Center
🇺🇸
Wauseon, Ohio, United States
Upper Valley Medical Center
🇺🇸
Troy, Ohio, United States
Clinton Memorial Hospital
🇺🇸
Wilmington, Ohio, United States
Danville Regional Medical Center
🇺🇸
Danville, Virginia, United States
Thomas Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Allan Blair Cancer Centre
🇨🇦
Regina, Saskatchewan, Canada
AnMed Health Hospital
🇺🇸
Anderson, South Carolina, United States
Rocky Mountain Oncology
🇺🇸
Casper, Wyoming, United States
Mid Dakota Clinic
🇺🇸
Bismarck, North Dakota, United States
Saint Anthony Hospital
🇺🇸
Lakewood, Colorado, United States
North Colorado Medical Center
🇺🇸
Greeley, Colorado, United States
Saint Mary Corwin Medical Center
🇺🇸
Pueblo, Colorado, United States
The Medical Center of Aurora
🇺🇸
Aurora, Colorado, United States
Saint John Hospital and Medical Center
🇺🇸
Detroit, Michigan, United States
Porter Adventist Hospital
🇺🇸
Denver, Colorado, United States
Exempla Saint Joseph Hospital
🇺🇸
Denver, Colorado, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸
Denver, Colorado, United States
Rose Medical Center
🇺🇸
Denver, Colorado, United States
Colorado Cancer Research Program CCOP
🇺🇸
Denver, Colorado, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Allegiance Health
🇺🇸
Jackson, Michigan, United States
Grand Rapids Clinical Oncology Program
🇺🇸
Grand Rapids, Michigan, United States
Saint Joseph Mercy Port Huron
🇺🇸
Port Huron, Michigan, United States
Saint Joseph Mercy Oakland
🇺🇸
Pontiac, Michigan, United States
Saint Charles Hospital
🇺🇸
Oregon, Ohio, United States
Kaiser Permanente-Stockton
🇺🇸
Stockton, California, United States
Grandview Hospital
🇺🇸
Dayton, Ohio, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Hopedale Medical Complex - Hospital
🇺🇸
Hopedale, Illinois, United States
Mercy Hospital
🇺🇸
Scranton, Pennsylvania, United States
Center for Cancer Care and Research
🇺🇸
Saint Louis, Missouri, United States
Altru Cancer Center
🇺🇸
Grand Forks, North Dakota, United States
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
🇺🇸
Maumee, Ohio, United States
Spartanburg Medical Center
🇺🇸
Spartanburg, South Carolina, United States
Good Samaritan Hospital - Dayton
🇺🇸
Dayton, Ohio, United States
Scranton Hematology Oncology
🇺🇸
Scranton, Pennsylvania, United States
Rapid City Regional Hospital
🇺🇸
Rapid City, South Dakota, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸
Wilkes-Barre, Pennsylvania, United States
Memorial Hospital Of Martinsville
🇺🇸
Martinsville, Virginia, United States
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
Kaiser Permanente-South Sacramento
🇺🇸
Sacramento, California, United States
Kaiser Permanente - Sacramento
🇺🇸
Sacramento, California, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
Michigan Cancer Research Consortium CCOP
🇺🇸
Ann Arbor, Michigan, United States
Southeast Cancer Consortium-Upstate NCORP
🇺🇸
Winston-Salem, North Carolina, United States
Mercy Capitol
🇺🇸
Des Moines, Iowa, United States
Iowa Methodist Medical Center
🇺🇸
Des Moines, Iowa, United States
Iowa Oncology Research Association CCOP
🇺🇸
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Laurel
🇺🇸
Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸
Des Moines, Iowa, United States
Iowa Lutheran Hospital
🇺🇸
Des Moines, Iowa, United States
Truman Medical Center
🇺🇸
Kansas City, Missouri, United States
Saint Luke's Cancer Institute
🇺🇸
Kansas City, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸
Kansas City, Missouri, United States
Saint Joseph Health Center
🇺🇸
Kansas City, Missouri, United States
North Kansas City Hospital
🇺🇸
Kansas City, Missouri, United States
Research Medical Center
🇺🇸
Kansas City, Missouri, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
Boulder Community Hospital
🇺🇸
Boulder, Colorado, United States
OSF Saint Francis Medical Center
🇺🇸
Peoria, Illinois, United States
McFarland Clinic PC-William R Bliss Cancer Center
🇺🇸
Ames, Iowa, United States
Riverview Medical Center/Booker Cancer Center
🇺🇸
Red Bank, New Jersey, United States