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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 Institute Buffalo, New York  14263
Mayo Clinic Rochester, Minnesota  55905
Hurley Medical Center Flint, Michigan  48503
Boulder Community Hospital Boulder, Colorado  80301-9019
Porter Adventist Hospital Denver, Colorado  80210
Rose Medical Center Denver, Colorado  80220
Swedish Medical Center Englewood, Colorado  80110
Sky Ridge Medical Center Lone Tree, Colorado  80124
North Suburban Medical Center Thornton, Colorado  80229
Hutchinson Area Health Care Hutchinson, Minnesota  55350
Meeker County Memorial Hospital Lichfield, Minnesota  55355
Geisinger Medical Center Danville, Pennsylvania  17822-0001
Loyola University Medical Center Maywood, Illinois  60153
Rapid City Regional Hospital Rapid City, South Dakota  57709
Methodist Medical Center of Illinois Peoria, Illinois  61636
Cape Cod Hospital Hyannis, Massachusetts  02601
Virginia Piper Cancer Institute Minneapolis, Minnesota  55407
Boston Medical Center Boston, Massachusetts  02118
Kaiser Permanente Medical Center - Santa Clara Santa Clara, California  95051-5386
Iowa Methodist Medical Center Des Moines, Iowa  50309
Iowa Lutheran Hospital Des Moines, Iowa  50316-2301
Great Falls Clinic Great Falls, Montana  59405
Mount Nittany Medical Center State College, Pennsylvania  16803
North Colorado Medical Center Greeley, Colorado  80631
McKee Medical Center Loveland, Colorado  80539
Munson Medical Center Traverse City, Michigan  49684
Northern Rockies Radiation Oncology Center Billings, Montana  59101
Bozeman Deaconess Hospital Bozeman, Montana  59715
Kalispell Medical Oncology Kalispell, Montana  59901
Kalispell Regional Medical Center Kalispell, Montana  59901
Welch Cancer Center Sheridan, Wyoming  82801
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center Columbus, Ohio  43210-1240
Memorial Hospital Carthage, Illinois  62321
Hematology and Oncology Associates Chicago, Illinois  60611
Galesburg Cottage Hospital Galesburg, Illinois  61401
Galesburg Clinic Galesburg, Illinois  61401
Mason District Hospital Havana, Illinois  62644
McDonough District Hospital Macomb, Illinois  61455
BroMenn Regional Medical Center Normal, Illinois  61761
Proctor Hospital Peoria, Illinois  61614
Perry Memorial Hospital Princeton, Illinois  61356
Genesis Medical Center - West Campus Davenport, Iowa  52804
Mecosta County Medical Center Big Rapids, Michigan  49307
Community Cancer Center of Monroe Monroe, Michigan  48162
Bismarck Cancer Center Bismarck, North Dakota  58501
Wood County Oncology Center Bowling Green, Ohio  43402
Grandview Hospital Dayton, Ohio  45405
Lima Memorial Hospital Lima, Ohio  45804
Northwest Ohio Oncology Center Maumee, Ohio  43537
Mercy Hospital of Tiffin Tiffin, Ohio  44883
Fulton County Health Center Wauseon, Ohio  43567
Danville Regional Medical Center Danville, Virginia  24541
Exempla Lutheran Medical Center Wheat Ridge, Colorado  80033
Eureka Hospital Eureka, Illinois  61530
Bristol Hospital Bristol, Connecticut  06011-0977
Graham Hospital Association Canton, Illinois  61520
Holy Family Medical Center Des Plaines, Illinois  60016
Hematology Oncology Associates of Illinois-Highland Park Highland Park, Illinois  60035
Saint Joseph Medical Center Joliet, Illinois  60435
Pekin Hospital Pekin, Illinois  61554
Medical Oncology and Hematology Associates Des Moines, Iowa  50309
Bixby Medical Center Adrian, Michigan  49221
Saint Joseph Mercy Hospital Ann Arbor, Michigan  48106
Regions Hospital Saint Paul, Minnesota  55101
Rice Memorial Hospital Willmar, Minnesota  56201
Altru Cancer Center Grand Forks, North Dakota  58206
Saint Luke's Hospital Maumee, Ohio  43537
Geisinger Medical Group State College, Pennsylvania  16801
Center for Cancer Care and Research St. Louis, Missouri  63141
Miami Valley Hospital Dayton, Ohio  45409
Spartanburg Regional Medical Center Spartanburg, South Carolina  29303
Hospital District Sixth of Harper County Anthony, Kansas  67003
Menorah Medical Center Overland Park, Kansas  66209
Shawnee Mission Medical Center Shawnee Mission, Kansas  66204
North Kansas City Hospital Kansas City, Missouri  64116
Research Medical Center Kansas City, Missouri  64132
Saint Luke's East - Lee's Summit Lee's Summit, Missouri  64086
Liberty Hospital Liberty, Missouri  64068
Heartland Regional Medical Center Saint Joseph, Missouri  64506
Bozeman Deaconess Cancer Center Bozeman, Montana  59715
Northern Montana Hospital Havre, Montana  59501
Wayne Hospital Greenville, Ohio  45331
Clinton Memorial Hospital Wilmington, Ohio  45177
Rocky Mountain Oncology Casper, Wyoming  82609
Longmont United Hospital Longmont, Colorado  80501
Greene Memorial Hospital Xenia, Ohio  45385
Greater Baltimore Medical Center Baltimore, Maryland  21204
Rutherford Hospital Rutherfordton, North Carolina  28139
Mayo Clinic in Arizona Scottsdale, Arizona  85259-5404
Mayo Clinic in Florida Jacksonville, Florida  32224
Memorial Medical Center Springfield, Illinois  62781
Metro Health Hospital Grand Rapids, Michigan  49506
Guardian Oncology and Center for Wellness Missoula, Montana  59804
Northwestern University Chicago, Illinois  60611
Tahoe Forest Cancer Center Truckee, California  96161
Hennepin County Medical Center Minneapolis, Minnesota  
Saint Louis University Hospital St. Louis, Missouri  63110-0250
University of Rochester Rochester, New York  14642
Toledo Clinic Oregon, Ohio  43616
Mid Dakota Clinic Bismarck, North Dakota  58501
Presbyterian - Saint Lukes Medical Center - Health One Denver, Colorado  80218
Montana Cancer Consortium CCOP Billings, Montana  59101
Flower Hospital Sylvania, Ohio  43560-2197
UC Davis Comprehensive Cancer Center Sacramento, California  95817
Thomas Jefferson University Hospital Philadelphia, Pennsylvania  19131
Decatur Memorial Hospital Decatur, Illinois  62526
Oncology Associates Cedar Rapids, Iowa  52403
Virginia Commonwealth University Richmond, Virginia  
Montana Cancer Specialists Missoula, Montana  59807-7877
Boca Raton Comprehensive Cancer Center Boca Raton, Florida  33486
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
OSF Saint Francis Medical Center Peoria, Illinois  61637
Kaiser Permanente, Fremont Fremont, California  94538
Kaiser Permanente, Hayward Hayward, California  94545
Fremont - Rideout Cancer Center Marysville, California  95901
Kaiser Permanente-Oakland Oakland, California  94611
Valley Care Health System - Pleasanton Pleasanton, California  94588
Kaiser Permanente-Redwood City Redwood City, California  94063
Kaiser Permanente-Richmond Richmond, California  94801
Kaiser Permanente-Roseville Roseville, California  95661
Kaiser Permanente-South Sacramento Sacramento, California  95823
Kaiser Permanente - Sacramento Sacramento, California  95825
Kaiser Permanente-San Francisco San Francisco, California  94115
Kaiser Permanente-Santa Teresa-San Jose San Jose, California  95119
Kaiser Permanente-San Rafael San Rafael, California  94903
Kaiser Permanente-Santa Rosa Santa Rosa, California  95403
Kaiser Permanente-South San Francisco South San Francisco, California  94080
Kaiser Permanente-Stockton Stockton, California  95210
Kaiser Permanente-Vallejo Vallejo, California  94589
Kaiser Permanente-Walnut Creek Walnut Creek, California  94596
The Medical Center of Aurora Aurora, Colorado  80012
Penrose-Saint Francis Healthcare Colorado Springs, Colorado  80907
Saint Anthony Central Hospital Denver, Colorado  80204
Exempla Saint Joseph Hospital Denver, Colorado  80218
Colorado Cancer Research Program CCOP Denver, Colorado  80224-2522
Saint Mary's Hospital and Regional Medical Center Grand Junction, Colorado  81502
Saint Mary Corwin Medical Center Pueblo, Colorado  81004
Middlesex Hospital Middletown, Connecticut  06457
Hopedale Medical Complex - Hospital Hopedale, Illinois  61747
Midwest Center for Hematology Oncology Joliet, Illinois  60432
North Shore Hematology Oncology Libertyville, Illinois  60048
Community Cancer Center Foundation Normal, Illinois  61761
Illinois CancerCare-Ottawa Clinic Ottawa, Illinois  61350
Ottawa Regional Hospital and Healthcare Center Ottawa, Illinois  61350
Pekin Cancer Treatment Center Pekin, Illinois  61554
Illinois Oncology Research Association CCOP Peoria, Illinois  61615
Illinois CancerCare-Peoria Peoria, Illinois  61615
Illinois Valley Hospital Peru, Illinois  61354
Hematology Oncology Associates of Illinois - Skokie Skokie, Illinois  60076
Saint Margaret's Hospital Spring Valley, Illinois  61362
Saint Francis Hospital and Health Centers Beech Grove, Indiana  46107
Reid Hospital and Health Care Services Richmond, Indiana  47374
McFarland Clinic Ames, Iowa  50010
Hematology Oncology Associates-Quad Cities Bettendorf, Iowa  52722
Cedar Rapids Oncology Association Cedar Rapids, Iowa  52403
Mercy Hospital Cedar Rapids, Iowa  52403
Medical Oncology and Hematology Associates-West Des Moines Clive, Iowa  50325
Genesis Medical Center - East Campus Davenport, Iowa  52803
Iowa Oncology Research Association CCOP Des Moines, Iowa  50309
Mercy Capitol Des Moines, Iowa  50307
Mercy Medical Center - Des Moines Des Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des Moines Des Moines, Iowa  50309
Mercy Medical Center-Sioux City Sioux City, Iowa  51104
Saint Luke's Regional Medical Center Sioux City, Iowa  51104
Siouxland Hematology - Oncology Associates Sioux City, Iowa  51101
Covenant Medical Center Waterloo, Iowa  50702
Stormont-Vail Regional Health Center Topeka, Kansas  66604
Caritas Saint Elizabeth's Medical Center Brighton, Massachusetts  02135-2997
Hickman Cancer Center Adrian, Michigan  49221
Michigan Cancer Research Consortium Community Clinical Oncology Program Ann Arbor, Michigan  48106
Oakwood Hospital Dearborn, Michigan  48123
Saint John Hospital and Medical Center Detroit, Michigan  48236
Grand Rapids Clinical Oncology Program Grand Rapids, Michigan  49503
Saint Mary's Health Care Grand Rapids, Michigan  49503
Spectrum Health at Butterworth Campus Grand Rapids, Michigan  49503
Allegiance Health Jackson, Michigan  49201
Sparrow Hospital Lansing, Michigan  48912
Saint Mary Mercy Hospital Livonia, Michigan  48154
Mercy Memorial Hospital Monroe, Michigan  48162
Mercy Health Partners-Mercy Campus Muskegon, Michigan  49443
Saint Joseph Mercy Oakland Pontiac, Michigan  48341-2985
Saint Joseph Mercy Port Huron Port Huron, Michigan  48060
Saint Mary's of Michigan Saginaw, Michigan  48601
Saint John Macomb-Oakland Hospital Warren, Michigan  48093
Saint Mary's Medical Center Duluth, Minnesota  55805
Miller-Dwan Hospital Duluth, Minnesota  55805
Saint John's Hospital - Healtheast Maplewood, Minnesota  55109
Saint Luke's Cancer Institute Kansas City, Missouri  64111
Saint Luke's Hospital of Kansas City Kansas City, Missouri  64111
Saint Joseph Health Center Kansas City, Missouri  64114
Liberty Radiation Oncology Clinic Kansas City, Missouri  64116
Truman Medical Center Kansas City, Missouri  64108
Missouri Baptist Medical Center Saint Louis, Missouri  63131
Hematology-Oncology Centers of the Northern Rockies PC Billings, Montana  59101
Saint Vincent Healthcare Billings, Montana  59101
Billings Clinic Billings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment Center Butte, Montana  59701
Berdeaux, Donald MD (UIA Investigator) Great Falls, Montana  59405
Saint Peter's Community Hospital Helena, Montana  59601
Glacier Oncology PLLC Kalispell, Montana  59901
Community Medical Hospital Missoula, Montana  59801
Saint Patrick Hospital - Community Hospital Missoula, Montana  59802
Good Samaritan Hospital Kearney, Nebraska  68847
Veterans Adminstration New Jersey Health Care System East Orange, New Jersey  07018-1095
Hunterdon Medical Center Flemington, New Jersey  08822
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County Mount Holly, New Jersey  08060
Virtua West Jersey Hospital Voorhees Voorhees, New Jersey  08043
State University of New York Upstate Medical University Syracuse, New York  13210
Wayne Memorial Hospital Goldsboro, North Carolina  27534
Margaret R Pardee Memorial Hospital Hendersonville, North Carolina  28791
Saint Alexius Medical Center Bismarck, North Dakota  58501
Medcenter One Health Systems Bismarck, North Dakota  58501
Good Samaritan Hospital - Dayton Dayton, Ohio  45406
Dayton CCOP Dayton, Ohio  45429
Samaritan North Health Center Dayton, Ohio  45415
Hematology Oncology Center Incorporated Elyria, Ohio  44035
Blanchard Valley Hospital Findlay, Ohio  45840
Atrium Medical Center-Middletown Regional Hospital Franklin, Ohio  45005-1066
Kettering Medical Center Kettering, Ohio  45429
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center Maumee, Ohio  43537
Saint Charles Hospital Oregon, Ohio  43616
North Coast Cancer Care Sandusky, Ohio  44870
Toledo Community Hospital Oncology Program CCOP Toledo, Ohio  43617
Mercy Cancer Center at Saint Anne Mercy Hospital Toledo, Ohio  43623
University of Toledo Toledo, Ohio  43614
The Toledo Hospital Toledo, Ohio  43606
Saint Vincent Mercy Medical Center Toledo, Ohio  43608
Upper Valley Medical Center Troy, Ohio  45373
Scranton Hematology Oncology Scranton, Pennsylvania  18510
Mercy Hospital Scranton, Pennsylvania  18501
Geisinger Wyoming Valley Wilkes-Barre, Pennsylvania  18711
AnMed Health Hospital Anderson, South Carolina  29621
Upstate Carolina CCOP Spartanburg, South Carolina  29303
Fredericksburg Oncology Inc Fredericksburg, Virginia  22401
Lynn Regional Cancer Center - West Boca Raton, Florida  33428
Illinois CancerCare-Bloomington Bloomington%, Illinois  61701
Illinois CancerCare-Canton Canton, Illinois  61520
Illinois CancerCare-Carthage Carthage, Illinois  62321
Illinois CancerCare-Eureka Eureka, Illinois  61530
Illinois CancerCare-Cottage Galesburg, Illinois  61401
Illinois CancerCare-Havana Havana, Illinois  62644
Illinois CancerCare-Kewanee Clinic Kewanee, Illinois  61443
Illinois CancerCare-Macomb Macomb, Illinois  61455
Illinois CancerCare-Monmouth Monmouth, Illinois  61462
DuPage Medical Group-Ogden Naperville, Illinois  60563
Illinois CancerCare-Community Cancer Center Normal, Illinois  61761
Illinois CancerCare-Pekin Pekin, Illinois  61603
Illinois CancerCare-Peru Peru, Illinois  61354
Illinois CancerCare-Princeton Princeton, Illinois  61356
Illinois CancerCare-Spring Valley Spring Valley, Illinois  61362
The Memorial Hospital at Easton Easton, Maryland  21601
Syracuse Veterans Administration Medical Center Syracuse, New York  13210
North Coast Cancer Care-Clyde Clyde, Ohio  43410
Kaiser Permanente-Deer Valley Medical Center Antioch, California  94531
Kaiser Permanente Medical Center-Vacaville Vacaville, California  95688
Hematology Oncology Associates-Berwyn Berwyn, Illinois  60402
OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC Peoria, Illinois  61615-7827
Saint Luke's South Hospital Overland Park, Kansas  66213
Memorial Hospital Of Martinsville Martinsville, Virginia  24115
Sparks Regional Medical Center Fort Smith, Arkansas  72901
Genesys Regional Medical Center-West Flint Campus Flint, Michigan  48532
Essentia Health Duluth Clinic CCOP Duluth, Minnesota  55805
Toledo Clinic Cancer Centers-Oregon Oregon, Ohio  43616
Geisinger Medical Center-Cancer Center Hazelton Hazleton, Pennsylvania  18201
Illinois Cancer Specialists-Niles Niles, Illinois  60714
Bronson Battle Creek Battle Creek, Michigan  49017
Riverview Medical Center/Booker Cancer Center Red Bank, New Jersey  07701