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Three-Arm Randomized Phase II Study of Carboplatin and Paclitaxel in Combination With Cetuximab, IMC-A12 or Both in Patients With Advanced Non-Small Cell Lung Cancer Who Will Not Receive Bevacizumab-Based Therapy


Phase 2
18 Years
N/A
Not Enrolling
Both
Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Thank you

Trial Information

Three-Arm Randomized Phase II Study of Carboplatin and Paclitaxel in Combination With Cetuximab, IMC-A12 or Both in Patients With Advanced Non-Small Cell Lung Cancer Who Will Not Receive Bevacizumab-Based Therapy


PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival of patients with NSCLC randomized to
carboplatin plus paclitaxel plus cetuximab or carboplatin plus paclitaxel plus IMC-A12
(cixutumumab) or carboplatin plus paclitaxel plus cetuximab plus IMC-A12.

SECONDARY OBJECTIVES:

I. To evaluate the response rate, disease control rate (complete response plus partial
response plus stable disease), and toxicities for each arm.

II. To evaluate EGFR by IHC, mutation, and gene copy number, IGF-1R and IGF-2R expression
(both phosphorylated and unphosphorylated states), expression of p-AKT by IHC, and k-ras
mutation.

III. Plasma-based biomarkers will be evaluated for total and free insulin-like growth factor
1 and 2, IGF-growth factor binding protein 3 (IGFBP3) and circulating levels of EGF and TGF
alpha.

IV. To evaluate overall survival on each of the three arms.

OUTLINE: This is a multicenter study. Patients are stratified according to gender and
histology (squamous cell vs non-squamous cell). Patients are randomized to 1 of 3 treatment
arms.

ARM I: Patients receive carboplatin intravenously (IV) over 15-30 minutes and paclitaxel IV
over 3 hours on days 1 and 22 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and
36. Treatment repeats every 42 days for 2 courses. Patients with stable or responding
disease after 2 courses proceed to maintenance therapy with cetuximab alone on days 1, 8,
15, 22, 29, and 36. Treatment with cetuximab repeats every 42 days in the absence of disease
progression or unacceptable toxicity.

ARM II: Patients receive carboplatin and paclitaxel as in arm I. Patients also receive
cixutumumab IV over 1 hour on days 1, 15, and 29. Treatment repeats every 42 days for 2
courses. Patients with stable or responding disease after 2 courses proceed to maintenance
therapy with cixutumumab alone on days 1, 15, and 29. Treatment with cixutumumab repeats
every 42 days in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive carboplatin, paclitaxel, and cetuximab as in arm I. Patients also
receive cixutumumab as in arm II. Treatment repeats every 42 days for 2 courses. Patients
with stable or responding disease after 2 courses proceed to maintenance therapy with
cetuximab as in arm I and cixutumumab as in arm II.

Tumor tissue samples are collected at baseline for analysis of EGFR expression by IHC,
mutation, and gene copy number; IGF-1R and IGF-2R expression (both phosphorylated and
unphosphorylated states); p-AKT expression by IHC; and k-ras mutation. Blood, serum, and
plasma samples are collected periodically for biomarker analysis.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 1 year.


Inclusion Criteria:



- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

- Stage IIIB disease

- T4, NX with nodule in ipsilateral lung lobe allowed provided patient is not
a candidate for combined chemotherapy and radiotherapy

- Stage IV disease (includes M1a and M1b)

- Measurable disease as defined by RECIST criteria

- Ineligible for or refused treatment with bevacizumab

- No small cell lung cancer or mixed small cell and NSCLC

- No untreated or symptomatic CNS metastases

- Patients with a history of CNS metastases that are definitively treated, stable,
and controlled are eligible provided the following criteria are met:

- Definitive therapy (surgery and/or radiotherapy) has been administered

- Not planning to undergo additional treatment for brain metastases

- Clinically stable

- Off corticosteroids or on a stable dose of corticosteroids for ≥ 14 days
before study entry

- ECOG performance status 0-1

- Leukocytes > 3,000/mm^3

- ANC > 1,500/mm^3

- Hemoglobin > 9 g/dL

- Platelet count > 100,000/mm^3

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST < 3 times ULN (< 5 times ULN if elevations due to liver metastases)

- Creatinine < 1.5 times ULN OR creatinine clearance > 60 mL/min

- Fasting serum glucose < 120 mg/dL

- PTT ≤ 1.2 times ULN and INR ≤ 1.5 (unless patient is on anticoagulation therapy)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after the
last dose of cixutumumab

- No poorly controlled diabetes mellitus

- Patients with a history of diabetes mellitus are eligible provided their blood
glucose is within normal range and they are on a stable dietary or therapeutic
regimen for this condition

- No peripheral neuropathy > grade 1 as per CTCAE v 4.0

- No history of or suspected interstitial pneumonitis or pulmonary fibrosis on imaging

- No significant uncontrolled cardiac disease within the past 6 months, including any
of the following:

- Uncontrolled hypertension (BP > 150/100 mm Hg)

- Unstable angina

- Recent myocardial infarction

- Uncontrolled congestive heart failure

- Cardiomyopathy with decreased ejection fraction

- No arterial thrombosis, pulmonary embolus, deep vein thrombosis, or hemorrhagic
disorders within the past 28 days

- No other prior or concurrent malignancy, except for the following:

- Curatively treated malignancy with no known active disease for ≥ 3 years AND is
considered to be at low risk for recurrence by the treating physician

- Adequately treated nonmelanoma skin cancer or lentigo maligna with no evidence
of disease

- Adequately treated cervical carcinoma in situ with no evidence of disease

- Prostatic intraepithelial neoplasia with no evidence of prostate cancer

- No history of any medical or psychiatric condition, addictive disorder, or laboratory
abnormality that, in the opinion of the investigator, may increase the risks
associated with study participation or study treatments or may interfere with the
conduct of the study or interpretation of study results

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to cixutumumab

- Concurrent therapeutic anticoagulation allowed provided there is no bleeding and
patient is on a stable dose of anticoagulation therapy (e.g., Warfarin with an INR of
2-3) for > 2 weeks prior to study entry

- No prior agents targeting the EGFR or IGFR pathways

- No prior therapy for advanced NSCLC, except for surgery and/or radiotherapy

- No prior systemic therapy, including bevacizumab for advanced stage NSCLC

- At least 21 days since prior radiotherapy

- More than 4 weeks since prior major surgery or hormonal therapy (other than hormone
replacement therapy) and recovered

- More than 1 year since prior neoadjuvant or adjuvant chemotherapy

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 Time Frame:

From randomization to death or disease progression, whichever occurs first, assessed up to 3 years

Safety Issue:

No

Principal Investigator

Nasser Hanna

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-01976

NCT ID:

NCT00986674

Start Date:

September 2009

Completion Date:

Related Keywords:

  • Recurrent 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

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
Bronson Methodist Hospital Kalamazoo, Michigan  49007
West Michigan Cancer Center Kalamazoo, Michigan  49007-3731
Borgess Medical Center Kalamazooaa, Michigan  49001
Fairview Ridges Hospital Burnsville, Minnesota  55337
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
Geisinger Medical Center Danville, Pennsylvania  17822-0001
Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania  19104-4283
Marshfield Clinic Marshfield, Wisconsin  54449
Methodist Medical Center of Illinois Peoria, Illinois  61636
Memorial Hospital of South Bend South Bend, Indiana  46601
Newark Beth Israel Medical Center Newark, New Jersey  07112
Via Christi Regional Medical Center Wichita, Kansas  67214
Scott and White Memorial Hospital Temple, Texas  76508
Medical Center of Central Georgia Macon, Georgia  31201
University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001
North Colorado Medical Center Greeley, Colorado  80631
McKee Medical Center Loveland, Colorado  80539
Cancer Center of Kansas - Chanute Chanute, Kansas  66720
Cancer Center of Kansas - Dodge City Dodge City, Kansas  67801
Cancer Center of Kansas - Newton Newton, Kansas  67114
Cancer Center of Kansas - Salina Salina, Kansas  67042
Cancer Center of Kansas - Wellington Wellington, Kansas  67152
Associates in Womens Health Wichita, Kansas  67203
Cancer Center of Kansas - Winfield Winfield, Kansas  67156
Adena Regional Medical Center Chillicothe, Ohio  54601
Grady Memorial Hospital Delaware, Ohio  43015
Fairfield Medical Center Lancaster, Ohio  43130
Paoli Memorial Hospital Paoli, Pennsylvania  19301-1792
Elkhart General Hospital Elkhart, Indiana  46515
University Medical Center of Southern Nevada Las Vegas, Nevada  89102
Memorial Hospital Carthage, Illinois  62321
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
Community Cancer Center of Monroe Monroe, Michigan  48162
Creighton University Medical Center Omaha, Nebraska  68131-2197
Lima Memorial Hospital Lima, Ohio  45804
Mercy Hospital of Tiffin Tiffin, Ohio  44883
Fulton County Health Center Wauseon, Ohio  43567
Bryn Mawr Hospital Bryn Mawr, Pennsylvania  19010
Exempla Lutheran Medical Center Wheat Ridge, Colorado  80033
Eureka Hospital Eureka, Illinois  61530
Mercy Hospital Coon Rapids, Minnesota  55433
Graham Hospital Association Canton, Illinois  61520
Holy Family Medical Center Des Plaines, Illinois  60016
Saint Joseph Medical Center Joliet, Illinois  60435
Trinity Medical Center Moline, Illinois  61265-1291
Pekin Hospital Pekin, Illinois  61554
Bixby Medical Center Adrian, Michigan  49221
Saint Joseph Mercy Hospital Ann Arbor, Michigan  48106
Fairview-Southdale Hospital Edina, Minnesota  55435
Abbott-Northwestern Hospital Minneapolis, Minnesota  55407
Saint Francis Regional Medical Center Shakopee, Minnesota  55379
Rice Memorial Hospital Willmar, Minnesota  56201
Saint Luke's Hospital Maumee, Ohio  43537
Lancaster General Hospital Lancaster, Pennsylvania  17604-3555
Geisinger Medical Group State College, Pennsylvania  16801
Fox Valley Hematology and Oncology Appleton, Wisconsin  54911
Cancer Center of Kansas - Fort Scott Fort Scott, Kansas  66701
Cancer Center of Kansas-Independence Independence, Kansas  67301
Lawrence Memorial Hospital Lawrence, Kansas  66044
Mary Rutan Hospital Bellefontaine, Ohio  43311
Knox Community Hospital Mount Vernon, Ohio  43050
Fisher-Titus Medical Center Norwalk, Ohio  44857
Marshfield Clinic Cancer Care at Regional Cancer Center Eau Claire, Wisconsin  54701
UW Cancer Center Johnson Creek Johnson Creek, Wisconsin  53038
Marshfield Clinic - Weston Center Weston, Wisconsin  54476
Marshfield Clinic - Wisconsin Rapids Center Wisconsin Rapids, Wisconsin  54494
Longmont United Hospital Longmont, Colorado  80501
Greater Baltimore Medical Center Baltimore, Maryland  21204
Manchester Memorial Hospital Manchester, Connecticut  06040-4188
University of Virginia Charlottesville, Virginia  22908
University of Pittsburgh Pittsburgh, Pennsylvania  15261
Case Western Reserve University Cleveland, Ohio  44106
Albert Einstein Medical Center Philadelphia, Pennsylvania  19141
Riverside Methodist Hospital Columbus, Ohio  43214
Licking Memorial Hospital Newark, Ohio  43055-2899
Columbus CCOP Columbus, Ohio  43206
Indiana University Medical Center Indianapolis, Indiana  46202
Presbyterian - Saint Lukes Medical Center - Health One Denver, Colorado  80218
Wichita CCOP Wichita, Kansas  67214-3882
Alegent Health Immanuel Medical Center Omaha, Nebraska  68122
Alegent Health Bergan Mercy Medical Center Omaha, Nebraska  68124
Flower Hospital Sylvania, Ohio  43560-2197
Metro-Minnesota CCOP St. Louis Park, Minnesota  
Lankenau Hospital Wynnewood, Pennsylvania  19096
Northern Indiana Cancer Research Consortium South Bend, Indiana  
OSF Saint Francis Medical Center Peoria, Illinois  61637
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
Danbury Hospital Danbury, Connecticut  06810
Saint Francis Hospital and Medical Center Hartford, Connecticut  06105
Evanston CCOP-NorthShore University HealthSystem Evanston, Illinois  60201
Stoffel, Thomas J MD (UIA Investigator) Moline, Illinois  61265
Garneau, Stewart C MD (UIA Investigator) Moline, Illinois  61265
Sharis, Christine M MD (UIA Investigator) Moline, Illinois  61265
Porubcin, Michael MD (UIA Investigator) Moline, Illinois  61265
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
Saint Margaret's Hospital Spring Valley, Illinois  61362
Richard L. Roudebush Veterans Affairs Medical Center Indianapolis, Indiana  46202
Wishard Hospital Indianapolis, Indiana  46202
Constantinou, Costas L MD (UIA Investigator) Bettendorf, Iowa  52722
Cedar Rapids Oncology Association Cedar Rapids, Iowa  52403
Mercy Hospital Cedar Rapids, Iowa  52403
Mercy Medical Center-Sioux City Sioux City, Iowa  51104
Saint Luke's Regional Medical Center Sioux City, Iowa  51104
Cancer Center of Kansas - El Dorado El Dorado, Kansas  67042
Cancer Center of Kansas-Kingman Kingman, Kansas  67068
Cancer Center of Kansas - Parsons Parsons, Kansas  67357
Cancer Center of Kansas - Pratt Pratt, Kansas  67124
Cancer Center of Kansas-Wichita Medical Arts Tower Wichita, Kansas  67208
Cancer Center of Kansas - Main Office Wichita, Kansas  67214
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
Green Bay Oncology - Escanaba Escanaba, Michigan  49431
Green Bay Oncology - Iron Mountain Iron Mountain, Michigan  49801
Allegiance Health Jackson, Michigan  49201
Sparrow Hospital Lansing, Michigan  48912
Saint Mary Mercy Hospital Livonia, Michigan  48154
Mercy Memorial Hospital Monroe, Michigan  48162
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
Lakeland Hospital St. Joseph, Michigan  49085
Saint John Macomb-Oakland Hospital Warren, Michigan  48093
Miller-Dwan Hospital Duluth, Minnesota  55805
Unity Hospital Fridley, Minnesota  55432
Saint John's Hospital - Healtheast Maplewood, Minnesota  55109
Minnesota Oncology Hematology PA-Maplewood Maplewood, Minnesota  55109
North Memorial Medical Health Center Robbinsdale, Minnesota  55422
Park Nicollet Clinic - Saint Louis Park Saint Louis Park, Minnesota  55416
Minnesota Oncology and Hematology PA-Woodbury Woodbury, Minnesota  55125
Lincoln Medical Education Foundation Cancer Resource Center Lincoln, Nebraska  68510
Missouri Valley Cancer Consortium CCOP Omaha, Nebraska  68106
Nevada Cancer Research Foundation CCOP Las Vegas, Nevada  89106
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
Doctors Hospital Columbus, Ohio  43228
Grant Medical Center Columbus, Ohio  43215
Mount Carmel Health Center West Columbus, Ohio  43222
Hematology Oncology Center Incorporated Elyria, Ohio  44035
Marietta Memorial Hospital Marietta, Ohio  45750
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
Saint Vincent Mercy Medical Center Toledo, Ohio  43608
Saint Ann's Hospital Westerville, Ohio  43081
Genesis HealthCare System Zanesville, Ohio  43701
Natalie W Bryant Cancer Center Tulsa, Oklahoma  74136
Pottstown Memorial Medical Center Pottstown, Pennsylvania  19464
Scranton Hematology Oncology Scranton, Pennsylvania  18510
Mercy Hospital Scranton, Pennsylvania  18501
Geisinger Wyoming Valley Wilkes-Barre, Pennsylvania  18711
Mainline Health CCOP Wynnewood, Pennsylvania  19096
Fredericksburg Oncology Inc Fredericksburg, Virginia  22401
Wheeling Hospital Wheeling, West Virginia  26003
Saint Vincent Hospital Green Bay, Wisconsin  54301
Green Bay Oncology Limited at Saint Mary's Hospital Green Bay, Wisconsin  54303
Saint Mary's Hospital Green Bay, Wisconsin  54303
Green Bay Oncology at Saint Vincent Hospital Green Bay, Wisconsin  54301-3526
UW Health Oncology - 1 South Park Madison, Wisconsin  53715
Bay Area Medical Center Marinette, Wisconsin  54143
Marshfield Clinic-Minocqua Center Minocqua, Wisconsin  54548
Green Bay Oncology - Oconto Falls Oconto Falls, Wisconsin  54154
Marshfield Clinic at James Beck Cancer Center Rhinelander, Wisconsin  54501
Marshfield Clinic-Rice Lake Center Rice Lake, Wisconsin  54868
Green Bay Oncology - Sturgeon Bay Sturgeon Bay, Wisconsin  54235
Marshfield Clinic-Wausau Center Wausau, Wisconsin  54401
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-Havana Havana, Illinois  62644
Illinois CancerCare-Kewanee Clinic Kewanee, Illinois  61443
Illinois CancerCare-Macomb Macomb, Illinois  61455
Illinois CancerCare-Monmouth Monmouth, Illinois  61462
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
Cancer Center of Kansas-Liberal Liberal, Kansas  67901
North Coast Cancer Care-Clyde Clyde, Ohio  43410
Vanderbilt-Ingram Cancer Center Cool Springs Franklin, Tennessee  37067
Nashville Oncology Associates PC Nashville, Tennessee  37203
West Virginia University Charleston Charleston, West Virginia  25304
Marshfield Clinic-Chippewa Center Chippewa Falls, Wisconsin  54729
Holy Family Memorial Hospital Manitowoc, Wisconsin  54221
Marshfield Clinic Cancer Care at Saint Michael's Hospital Stevens Point, Wisconsin  54481
Riverview Hospital Wisconsin Rapids, Wisconsin  54494
Hinsdale Hematology Oncology Associates Incorporated Hinsdale, Illinois  60521
Spector, David MD (UIA Investigator) Moline, Illinois  61265
UHHS-Chagrin Highlands Medical Center Orange Village, Ohio  44122
UHHS-Westlake Medical Center Westlake, Ohio  44145
Gundersen Lutheran La Crosse, Wisconsin  54601
New York Oncology Hematology PC -Albany Medical Center Albany, New York  12208
New York Oncology Hematology PC - Albany Albany, New York  12206
New York Oncology Hematology PC - Amsterdam Amsterdam, New York  12010
New York Oncology Hematology PC-Hudson Hudson, New York  12534
New York Oncology Hematology PC - Latham Latham, New York  12110
New York Oncology Hematology PC - Rexford Rexford, New York  12148
New York Oncology Hematology PC - Troy Troy, New York  12180
Stanford University Hospitals and Clinics Stanford, California  94305
Siouxland Hematology Oncology Associates Sioux City, Iowa  51101
IU Health Arnett Lafayette, Indiana  
Oncology Associates at Mercy Medical Center Cedar Rapids, Iowa  52403
Marie Yeager Cancer Center Saint Joseph, Michigan  49085
Summa Akron City Hospital Akron, Ohio  44304
The Toledo Hospital/Toledo Children's Hospital Toledo, Ohio  43606
Genesys Regional Medical Center-West Flint Campus Flint, Michigan  48532
Essentia Health Duluth Clinic CCOP Duluth, Minnesota  55805
Essentia Health Saint Mary's Medical Center Duluth, Minnesota  55805
Toledo Clinic Cancer Centers-Oregon Oregon, Ohio  43616
Geisinger Medical Center-Cancer Center Hazelton Hazleton, Pennsylvania  18201
Community Howard Regional Health Kokomo, Indiana  46904
Indiana University Health La Porte Hospital La Porte, Indiana  46350
Saint Joseph Regional Medical Center-Mishawaka Mishawaka, Indiana  46545-1470
Springfield Regional Medical Center Springfield, Ohio  45505
Toledo Clinic Cancer Centers-Bowling Green Bowling Green, Ohio  43402
Toledo Clinic Cancer Centers-Maumee Maumee, Ohio  43537-1839
Toledo Clinic Cancer Centers-Toledo Toledo, Ohio  43623