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A Phase III Biomarker Validation Study of Second-line Therapy in Patients With Advanced Non- Small Cell Lung Cancer (NSCLC) Randomized to Pemetrexed Versus Erlotinib


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Recurrent Non-small Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Thank you

Trial Information

A Phase III Biomarker Validation Study of Second-line Therapy in Patients With Advanced Non- Small Cell Lung Cancer (NSCLC) Randomized to Pemetrexed Versus Erlotinib


PRIMARY OBJECTIVES:

I. Compare the progression-free survival of epidermal growth factor receptor (EGFR)
FISH-positive or -negative patients with advanced non-small cell lung cancer treated with
erlotinib hydrochloride versus pemetrexed disodium as second-line therapy.

Secondary I. Compare the overall survival, confirmed response rate, and adverse event
profile in these patients based on EGFR-FISH status (positive vs negative).

II. Compare the progression-free survival, overall survival, confirmed response rate, and
adverse event profile in these patients based on EGFR expression as measured by
immunohistochemistry (IHC).

III. Compare the progression-free survival, overall survival, confirmed response rate, and
adverse event profile in these patients based on EGFR gene mutation status.

IV. Evaluate the prognostic effect of EGFR copy number, as measured by FISH, on the outcome
of these patients.

V. Evaluate the prognostic effect of EGFR expression, as measured by IHC, on the outcome of
these patients.

VI. Evaluate the prognostic effect of EGFR mutation status on the outcome of these patients.

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

VIII. 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 hydrochloride, either singly or in combination, play a role in the efficacy
and/or toxicity of erlotinib hydrochloride.

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

X. Evaluate thymidylate synthase, dihydrofolate reductase, 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 disodium.

XI. Evaluate the Ras mutation status, EGFR mutation status, and epithelial to mesenchymal
transition status (E-cadherin expression and vimentin expression) in tumor samples, as
measured by IHC, as predictors of survival and response to treatment with erlotinib
hydrochloride.

OUTLINE: This is a multicenter study. Patients are stratified according to FISH status
(negative vs positive), ECOG performance status (0 vs 1 vs 2), gender, smoking status (never
smoked vs light smoker [≤ 15 pack years] vs heavy smoker [> 15 pack years]), disease
histology (adenocarcinoma vs other), and best response to prior chemotherapy (complete
response/partial response vs stable disease vs progressive disease). Patients are randomized
to 1 of 2 treatment arms.

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

ARM II: 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. Tumor tissue
samples are collected at baseline for correlative laboratory studies, including analysis of
epidermal growth factor receptor (EGFR) gene expression by FISH; EGFR protein expression by
immunohistochemistry (IHC); EGFR and K-ras mutation status; epithelial to mesenchymal
transition status (E-cadherin expression and vimentin expression) by IHC; thymidylate
synthase, dihydrofolate reductase, and GAR formyltransferase gene expression by quantitative
polymerase chain reaction; and methylthioadenosine phosphorylase gene expression by IHC.

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


Inclusion Criteria:



- Histologically confirmed non-small cell lung cancer (NSCLC), either oninitial
diagnosis or at the time of disease recurrence/progression

- Mixed histology allowed if all components are consistent with NSCLC

- Recurrent or progressive disease

- 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
CT scan

- Measurable disease must be outside of any previously irradiated treatment
field(s) unless there is disease progression or recurrence within the irradiated
field(s)

- No nonmeasurable disease only, defined as any of the following:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural/pericardial effusion

- Inflammatory breast disease

- Lymphangitis cutis/pulmonis

- Abdominal masses not confirmed and followed by imaging techniques

- Cystic lesions

- Single disease site in prior radiotherapy field

- Tumor tissue samples must be available and adequate for epidermal growth factor
receptor (EGFR) evaluation by FISH

- Previously treated with only one cytotoxic chemotherapy regimen for advanced disease

- Neoadjuvant/adjuvant cytotoxic chemotherapy administered< 12 months (from date
chemotherapy was started) prior to study entry will be counted as one prior
treatment

- Neoadjuvant/adjuvant chemotherapy administered ≥ 12 months prior to study entry
and use of targeted agents (e.g., monoclonal antibodies) will not be counted as
one prior treatment

- No symptomatic serosal effusion (≥ grade 2 dyspnea as measured by CTCAE v3.0) that is
not amenable to drainage

- No brain metastasis, unless the following criteria are met:

- Brain metastasis is stable and has been previously treated with either
whole-brain radiotherapy or gamma-knife surgery

- More than 14 days since prior steroid treatment

- ECOG performance status 0-2

- Life expectancy ≥ 12 weeks

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 10 g/dL

- Total bilirubin normal (ULN) OR direct bilirubinnormal

- AST and ALT ≤ 2.5 times ULN

- INR ≤ 1.5

- Creatinine clearance ≥ 45 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to take folic acid, vitamin B_12 supplementation, and dexamethasone

- No known HIV positivity

- No clinically significant infection

- No impaired 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, or bowel obstruction)

- No serious condition that, in the opinion of the investigator, would preclude the
patient's ability to complete the study therapy or increase the risk for serious
adverse events

- No other invasive malignant solid tumor or hematologic malignancy, except for any of
the following:

- Prior carcinoma in situ, regardless of organ involvement, or nonmelanoma
cutaneous carcinoma that was definitively treated ≥ 3 years ago with no
subsequent evidence of recurrence

- Other prior malignancy diagnosed and definitively treated ≥ 5 years ago with no
subsequent evidence of recurrence

- Prior breast cancer that was definitively treated > 5 years ago allowed
provided patient is not receiving aromatase inhibitors

- Prio rlow-grade (Gleason score ≤ 6) localized prostate cancer that was
diagnosed < 3 years ago allowed

- Concurrent medications to maintain disease remission allowed

- No concurrent severe and/or uncontrolled medical condition, including any of the
following:

- Angina pectoris

- Congestive heart failure within the past 3 months, unless ejection fraction >
40%

- Myocardial infarction within the past 6 months

- Cardiac arrhythmia

- Diabetes mellitus

- Hypertension

- Any other severe underlying disease that, in the judgment of the investigator,
would preclude study entry

- No respiratory symptoms > CTCAE grade 1

- No significant traumatic injury within the past 4 weeks

- No concurrent prophylactic colony-stimulating factors

- Recovered from prior radiotherapy, except for alopecia

- No prior radiotherapy to > 25% of bone marrow

- No prior EGFR tyrosine kinase inhibitors or pemetrexed disodium

- More than 3 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)

- More than 2 weeks since prior immunotherapy, gene therapy, or other biologic therapy

- More than 2 weeks since prior limited-field radiotherapy (4 weeks for full-field
radiotherapy)

- More than 2 weeks since prior minor surgery*

- More than 4 weeks since prior major surgery (i.e., laparotomy)* or open biopsy

- More than 4 weeks since prior hormonal therapy

- More than 4 weeks since prior and no other concurrent ancillary therapy considered
investigational (i.e., utilized for a non-FDA-approved indication and in the context
of a research investigation)

- No aspirin dose ≥ 1.3 g/day for ≥ 10days before, during, and for ≥ 10 days after
treatment with pemetrexed disodium

- No other concurrent chemotherapy, immunotherapy, hormonal therapy, or radiotherapy

- Radiotherapy for symptom palliation (e.g., painful pre-existing bony metastasis)
allowed

- No other concurrent anticancer therapy

- No concurrent major surgery

- No concurrent antiretroviral therapy

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS)

Outcome Description:

Estimated using the method of Kaplan-Meier survival curves and a 1-sided stratified log rank test [accounting for all the stratification factors except FISH status and cooperative group] will be used to compare PFS between the erlotinib and pemetrexed arms within the FISH(+) and FISH(-) subgroups. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess whether the distribution of PFS times differ with respect to treatment regimen after having adjusted for the stratification factors as well as other potential prognostic and treatment covariates.

Outcome Time Frame:

Time from randomization to the first date of documented disease progression or death, assessed up to 5 years

Safety Issue:

No

Principal Investigator

Alex Adjei

Investigator Role:

Principal Investigator

Investigator Affiliation:

North Central Cancer Treatment Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00663

NCT ID:

NCT00738881

Start Date:

October 2008

Completion Date:

Related Keywords:

  • Recurrent Non-Small Cell Lung Cancer
  • Stage IIIA Non-Small Cell Lung Cancer
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Mayo ClinicRochester, Minnesota  55905
Hurley Medical CenterFlint, Michigan  48503
Boulder Community HospitalBoulder, Colorado  80301-9019
Porter Adventist HospitalDenver, Colorado  80210
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
Sky Ridge Medical CenterLone Tree, Colorado  80124
North Suburban Medical CenterThornton, Colorado  80229
Hutchinson Area Health CareHutchinson, Minnesota  55350
Meeker County Memorial HospitalLichfield, Minnesota  55355
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Loyola University Medical CenterMaywood, Illinois  60153
Rapid City Regional HospitalRapid City, South Dakota  57709
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Cape Cod HospitalHyannis, Massachusetts  02601
Virginia Piper Cancer InstituteMinneapolis, Minnesota  55407
Boston Medical CenterBoston, Massachusetts  02118
Kaiser Permanente Medical Center - Santa ClaraSanta Clara, California  95051-5386
Iowa Methodist Medical CenterDes Moines, Iowa  50309
Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Great Falls ClinicGreat Falls, Montana  59405
Mount Nittany Medical CenterState College, Pennsylvania  16803
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Munson Medical CenterTraverse City, Michigan  49684
Northern Rockies Radiation Oncology CenterBillings, Montana  59101
Bozeman Deaconess HospitalBozeman, Montana  59715
Kalispell Medical OncologyKalispell, Montana  59901
Kalispell Regional Medical CenterKalispell, Montana  59901
Welch Cancer CenterSheridan, Wyoming  82801
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Memorial HospitalCarthage, Illinois  62321
Hematology and Oncology AssociatesChicago, Illinois  60611
Galesburg Cottage HospitalGalesburg, Illinois  61401
Galesburg ClinicGalesburg, Illinois  61401
Mason District HospitalHavana, Illinois  62644
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Proctor HospitalPeoria, Illinois  61614
Perry Memorial HospitalPrinceton, Illinois  61356
Genesis Medical Center - West CampusDavenport, Iowa  52804
Mecosta County Medical CenterBig Rapids, Michigan  49307
Community Cancer Center of MonroeMonroe, Michigan  48162
Bismarck Cancer CenterBismarck, North Dakota  58501
Wood County Oncology CenterBowling Green, Ohio  43402
Grandview HospitalDayton, Ohio  45405
Lima Memorial HospitalLima, Ohio  45804
Northwest Ohio Oncology CenterMaumee, Ohio  43537
Mercy Hospital of TiffinTiffin, Ohio  44883
Fulton County Health CenterWauseon, Ohio  43567
Danville Regional Medical CenterDanville, Virginia  24541
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Eureka HospitalEureka, Illinois  61530
Bristol HospitalBristol, Connecticut  06011-0977
Graham Hospital AssociationCanton, Illinois  61520
Holy Family Medical CenterDes Plaines, Illinois  60016
Hematology Oncology Associates of Illinois-Highland ParkHighland Park, Illinois  60035
Saint Joseph Medical CenterJoliet, Illinois  60435
Pekin HospitalPekin, Illinois  61554
Medical Oncology and Hematology AssociatesDes Moines, Iowa  50309
Bixby Medical CenterAdrian, Michigan  49221
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Regions HospitalSaint Paul, Minnesota  55101
Rice Memorial HospitalWillmar, Minnesota  56201
Altru Cancer CenterGrand Forks, North Dakota  58206
Saint Luke's HospitalMaumee, Ohio  43537
Geisinger Medical GroupState College, Pennsylvania  16801
Center for Cancer Care and ResearchSt. Louis, Missouri  63141
Miami Valley HospitalDayton, Ohio  45409
Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Hospital District Sixth of Harper CountyAnthony, Kansas  67003
Menorah Medical CenterOverland Park, Kansas  66209
Shawnee Mission Medical CenterShawnee Mission, Kansas  66204
North Kansas City HospitalKansas City, Missouri  64116
Research Medical CenterKansas City, Missouri  64132
Saint Luke's East - Lee's SummitLee's Summit, Missouri  64086
Liberty HospitalLiberty, Missouri  64068
Heartland Regional Medical CenterSaint Joseph, Missouri  64506
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
Northern Montana HospitalHavre, Montana  59501
Wayne HospitalGreenville, Ohio  45331
Clinton Memorial HospitalWilmington, Ohio  45177
Rocky Mountain OncologyCasper, Wyoming  82609
Longmont United HospitalLongmont, Colorado  80501
Greene Memorial HospitalXenia, Ohio  45385
Greater Baltimore Medical CenterBaltimore, Maryland  21204
Rutherford HospitalRutherfordton, North Carolina  28139
Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404
Mayo Clinic in FloridaJacksonville, Florida  32224
Memorial Medical CenterSpringfield, Illinois  62781
Metro Health HospitalGrand Rapids, Michigan  49506
Guardian Oncology and Center for WellnessMissoula, Montana  59804
Northwestern UniversityChicago, Illinois  60611
Tahoe Forest Cancer CenterTruckee, California  96161
Hennepin County Medical CenterMinneapolis, Minnesota  
Saint Louis University HospitalSt. Louis, Missouri  63110-0250
University of RochesterRochester, New York  14642
Toledo ClinicOregon, Ohio  43616
Mid Dakota ClinicBismarck, North Dakota  58501
Presbyterian - Saint Lukes Medical Center - Health OneDenver, Colorado  80218
Montana Cancer Consortium CCOPBillings, Montana  59101
Flower HospitalSylvania, Ohio  43560-2197
UC Davis Comprehensive Cancer CenterSacramento, California  95817
Thomas Jefferson University HospitalPhiladelphia, Pennsylvania  19131
Decatur Memorial HospitalDecatur, Illinois  62526
Oncology AssociatesCedar Rapids, Iowa  52403
Virginia Commonwealth UniversityRichmond, Virginia  
Montana Cancer SpecialistsMissoula, Montana  59807-7877
Boca Raton Comprehensive Cancer CenterBoca Raton, Florida  33486
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
OSF Saint Francis Medical CenterPeoria, Illinois  61637
Kaiser Permanente, FremontFremont, California  94538
Kaiser Permanente, HaywardHayward, California  94545
Fremont - Rideout Cancer CenterMarysville, California  95901
Kaiser Permanente-OaklandOakland, California  94611
Valley Care Health System - PleasantonPleasanton, California  94588
Kaiser Permanente-Redwood CityRedwood City, California  94063
Kaiser Permanente-RichmondRichmond, California  94801
Kaiser Permanente-RosevilleRoseville, California  95661
Kaiser Permanente-South SacramentoSacramento, California  95823
Kaiser Permanente - SacramentoSacramento, California  95825
Kaiser Permanente-San FranciscoSan Francisco, California  94115
Kaiser Permanente-Santa Teresa-San JoseSan Jose, California  95119
Kaiser Permanente-San RafaelSan Rafael, California  94903
Kaiser Permanente-Santa RosaSanta Rosa, California  95403
Kaiser Permanente-South San FranciscoSouth San Francisco, California  94080
Kaiser Permanente-StocktonStockton, California  95210
Kaiser Permanente-VallejoVallejo, California  94589
Kaiser Permanente-Walnut CreekWalnut Creek, California  94596
The Medical Center of AuroraAurora, Colorado  80012
Penrose-Saint Francis HealthcareColorado Springs, Colorado  80907
Saint Anthony Central HospitalDenver, Colorado  80204
Exempla Saint Joseph HospitalDenver, Colorado  80218
Colorado Cancer Research Program CCOPDenver, Colorado  80224-2522
Saint Mary's Hospital and Regional Medical CenterGrand Junction, Colorado  81502
Saint Mary Corwin Medical CenterPueblo, Colorado  81004
Middlesex HospitalMiddletown, Connecticut  06457
Hopedale Medical Complex - HospitalHopedale, Illinois  61747
Midwest Center for Hematology OncologyJoliet, Illinois  60432
North Shore Hematology OncologyLibertyville, Illinois  60048
Community Cancer Center FoundationNormal, Illinois  61761
Illinois CancerCare-Ottawa ClinicOttawa, Illinois  61350
Ottawa Regional Hospital and Healthcare CenterOttawa, Illinois  61350
Pekin Cancer Treatment CenterPekin, Illinois  61554
Illinois Oncology Research Association CCOPPeoria, Illinois  61615
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Illinois Valley HospitalPeru, Illinois  61354
Hematology Oncology Associates of Illinois - SkokieSkokie, Illinois  60076
Saint Margaret's HospitalSpring Valley, Illinois  61362
Saint Francis Hospital and Health CentersBeech Grove, Indiana  46107
Reid Hospital and Health Care ServicesRichmond, Indiana  47374
McFarland ClinicAmes, Iowa  50010
Hematology Oncology Associates-Quad CitiesBettendorf, Iowa  52722
Cedar Rapids Oncology AssociationCedar Rapids, Iowa  52403
Mercy HospitalCedar Rapids, Iowa  52403
Medical Oncology and Hematology Associates-West Des MoinesClive, Iowa  50325
Genesis Medical Center - East CampusDavenport, Iowa  52803
Iowa Oncology Research Association CCOPDes Moines, Iowa  50309
Mercy CapitolDes Moines, Iowa  50307
Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des MoinesDes Moines, Iowa  50309
Mercy Medical Center-Sioux CitySioux City, Iowa  51104
Saint Luke's Regional Medical CenterSioux City, Iowa  51104
Siouxland Hematology - Oncology AssociatesSioux City, Iowa  51101
Covenant Medical CenterWaterloo, Iowa  50702
Stormont-Vail Regional Health CenterTopeka, Kansas  66604
Caritas Saint Elizabeth's Medical CenterBrighton, Massachusetts  02135-2997
Hickman Cancer CenterAdrian, Michigan  49221
Michigan Cancer Research Consortium Community Clinical Oncology ProgramAnn Arbor, Michigan  48106
Oakwood HospitalDearborn, Michigan  48123
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Grand Rapids Clinical Oncology ProgramGrand Rapids, Michigan  49503
Saint Mary's Health CareGrand Rapids, Michigan  49503
Spectrum Health at Butterworth CampusGrand Rapids, Michigan  49503
Allegiance HealthJackson, Michigan  49201
Sparrow HospitalLansing, Michigan  48912
Saint Mary Mercy HospitalLivonia, Michigan  48154
Mercy Memorial HospitalMonroe, Michigan  48162
Mercy Health Partners-Mercy CampusMuskegon, Michigan  49443
Saint Joseph Mercy OaklandPontiac, Michigan  48341-2985
Saint Joseph Mercy Port HuronPort Huron, Michigan  48060
Saint Mary's of MichiganSaginaw, Michigan  48601
Saint John Macomb-Oakland HospitalWarren, Michigan  48093
Saint Mary's Medical CenterDuluth, Minnesota  55805
Miller-Dwan HospitalDuluth, Minnesota  55805
Saint John's Hospital - HealtheastMaplewood, Minnesota  55109
Saint Luke's Cancer InstituteKansas City, Missouri  64111
Saint Luke's Hospital of Kansas CityKansas City, Missouri  64111
Saint Joseph Health CenterKansas City, Missouri  64114
Liberty Radiation Oncology ClinicKansas City, Missouri  64116
Truman Medical CenterKansas City, Missouri  64108
Missouri Baptist Medical CenterSaint Louis, Missouri  63131
Hematology-Oncology Centers of the Northern Rockies PCBillings, Montana  59101
Saint Vincent HealthcareBillings, Montana  59101
Billings ClinicBillings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment CenterButte, Montana  59701
Berdeaux, Donald MD (UIA Investigator)Great Falls, Montana  59405
Saint Peter's Community HospitalHelena, Montana  59601
Glacier Oncology PLLCKalispell, Montana  59901
Community Medical HospitalMissoula, Montana  59801
Saint Patrick Hospital - Community HospitalMissoula, Montana  59802
Good Samaritan HospitalKearney, Nebraska  68847
Veterans Adminstration New Jersey Health Care SystemEast Orange, New Jersey  07018-1095
Hunterdon Medical CenterFlemington, New Jersey  08822
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington CountyMount Holly, New Jersey  08060
Virtua West Jersey Hospital VoorheesVoorhees, New Jersey  08043
State University of New York Upstate Medical UniversitySyracuse, New York  13210
Wayne Memorial HospitalGoldsboro, North Carolina  27534
Margaret R Pardee Memorial HospitalHendersonville, North Carolina  28791
Saint Alexius Medical CenterBismarck, North Dakota  58501
Medcenter One Health SystemsBismarck, North Dakota  58501
Good Samaritan Hospital - DaytonDayton, Ohio  45406
Dayton CCOPDayton, Ohio  45429
Samaritan North Health CenterDayton, Ohio  45415
Hematology Oncology Center IncorporatedElyria, Ohio  44035
Blanchard Valley HospitalFindlay, Ohio  45840
Atrium Medical Center-Middletown Regional HospitalFranklin, Ohio  45005-1066
Kettering Medical CenterKettering, Ohio  45429
Toledo Radiation Oncology at Northwest Ohio Onocolgy CenterMaumee, Ohio  43537
Saint Charles HospitalOregon, Ohio  43616
North Coast Cancer CareSandusky, Ohio  44870
Toledo Community Hospital Oncology Program CCOPToledo, Ohio  43617
Mercy Cancer Center at Saint Anne Mercy HospitalToledo, Ohio  43623
University of ToledoToledo, Ohio  43614
The Toledo HospitalToledo, Ohio  43606
Saint Vincent Mercy Medical CenterToledo, Ohio  43608
Upper Valley Medical CenterTroy, Ohio  45373
Scranton Hematology OncologyScranton, Pennsylvania  18510
Mercy HospitalScranton, Pennsylvania  18501
Geisinger Wyoming ValleyWilkes-Barre, Pennsylvania  18711
AnMed Health HospitalAnderson, South Carolina  29621
Upstate Carolina CCOPSpartanburg, South Carolina  29303
Fredericksburg Oncology IncFredericksburg, Virginia  22401
Lynn Regional Cancer Center - WestBoca Raton, Florida  33428
Illinois CancerCare-BloomingtonBloomington%, Illinois  61701
Illinois CancerCare-CantonCanton, Illinois  61520
Illinois CancerCare-CarthageCarthage, Illinois  62321
Illinois CancerCare-EurekaEureka, Illinois  61530
Illinois CancerCare-CottageGalesburg, Illinois  61401
Illinois CancerCare-HavanaHavana, Illinois  62644
Illinois CancerCare-Kewanee ClinicKewanee, Illinois  61443
Illinois CancerCare-MacombMacomb, Illinois  61455
Illinois CancerCare-MonmouthMonmouth, Illinois  61462
DuPage Medical Group-OgdenNaperville, Illinois  60563
Illinois CancerCare-Community Cancer CenterNormal, Illinois  61761
Illinois CancerCare-PekinPekin, Illinois  61603
Illinois CancerCare-PeruPeru, Illinois  61354
Illinois CancerCare-PrincetonPrinceton, Illinois  61356
Illinois CancerCare-Spring ValleySpring Valley, Illinois  61362
The Memorial Hospital at EastonEaston, Maryland  21601
Syracuse Veterans Administration Medical CenterSyracuse, New York  13210
North Coast Cancer Care-ClydeClyde, Ohio  43410
Kaiser Permanente-Deer Valley Medical CenterAntioch, California  94531
Kaiser Permanente Medical Center-VacavilleVacaville, California  95688
Hematology Oncology Associates-BerwynBerwyn, Illinois  60402
OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CCPeoria, Illinois  61615-7827
Saint Luke's South HospitalOverland Park, Kansas  66213
Memorial Hospital Of MartinsvilleMartinsville, Virginia  24115
Sparks Regional Medical CenterFort Smith, Arkansas  72901
Genesys Regional Medical Center-West Flint CampusFlint, Michigan  48532
Essentia Health Duluth Clinic CCOPDuluth, Minnesota  55805
Toledo Clinic Cancer Centers-OregonOregon, Ohio  43616
Geisinger Medical Center-Cancer Center HazeltonHazleton, Pennsylvania  18201
Illinois Cancer Specialists-NilesNiles, Illinois  60714
Bronson Battle CreekBattle Creek, Michigan  49017
Riverview Medical Center/Booker Cancer CenterRed Bank, New Jersey  07701