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A Phase III Randomized Trial of Metformin Versus Placebo on Recurrence and Survival in Early Stage Breast Cancer


Phase 3
18 Years
74 Years
Open (Enrolling)
Both
Breast Cancer

Thank you

Trial Information

A Phase III Randomized Trial of Metformin Versus Placebo on Recurrence and Survival in Early Stage Breast Cancer


OBJECTIVES:

Primary

- To compare invasive disease-free survival of patients with early-stage breast cancer
treated with metformin vs placebo in addition to standard adjuvant therapy.

Secondary

- To compare overall survival of these patients.

- To compare distant disease-free survival of these patients.

- To compare breast cancer-free interval in these patients.

- To compare invasive disease-free survival of patients who are hormone receptor-negative
(both estrogen receptor and progesterone receptor).

- To compare changes in body mass index in these patients.

- To compare adverse events in these patients.

- To compare other medical endpoints, including a new diagnosis of diabetes mellitus or
cardiovascular hospitalization (including an emergency room visit or overnight stay) or
death (stroke or myocardial infarction), in these patients.

- To compare health-related quality of life measured using the EORTC QLQ-C30
(supplemented by a trial-specific checklist), the Block Alive Screener, and physical
activity items from the Nurses Health Study Questionnaire II on a subset of these
patients.

- To compare embedded correlative science outcomes including plasma insulin and molecular
markers of metformin action in these patients.

- To compare metabolic parameters including metabolic components of the insulin
resistance syndrome as defined by the ATP III criteria in a subset of these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to hormone-receptor
status (estrogen receptor- and/or progesterone receptor- positive vs both receptors
negative), body mass index (≤ 30 vs > 30 kg/m²), HER2 status (positive vs negative), and
prior chemotherapy (any vs none). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral metformin hydrochloride twice daily (once daily in weeks
1-4). Treatment continues for up to 5 years in the absence of disease progression or
unacceptable toxicity.

- Arm II: Patients receive oral placebo twice daily (once daily in weeks 1-4). Treatment
continues for up to 5 years in the absence of disease progression or unacceptable
toxicity.

Blood and tumor samples are collected periodically for correlative studies.

Patients may complete quality-of-life, physical activity, and diet questionnaires at
baseline and at 6, 12, 24, 36, 48, and 60 months. (Sub-set of patients).

After completion of study treatment, patients are followed annually.

Inclusion Criteria


Eligibility Criteria:

- Subjects must have histologically confirmed invasive breast cancer and be enrolled in
the trial within 12 months after the first histologic diagnosis of invasive breast
cancer. A core biopsy interpreted as invasive cancer meets this criterion; otherwise,
the date of first histologic diagnosis will be the date of first surgical procedure
that identifies invasive cancer (biopsy, lumpectomy or mastectomy). Neoadjuvant
subjects should have no evidence of clinical T4 disease prior to chemotherapy and
surgery. Bilateral breast carcinoma is allowed provided diagnoses are synchronous -
that is, within 3 months of one another - and at least one of the two breast
carcinomas meet the eligibility criteria and neither violates the eligibility
criteria.

- All subjects (both adjuvant and neo-adjuvant) must have sentinel lymph node biopsy
and/or axillary lymph node dissection.

Sentinel lymph node biopsy alone is allowed in the following instances:

1. sentinel lymph node biopsy is negative: pN0

2. sentinel lymph node biopsy is positive for isolated tumour cells only: pN0 (i+)

3. * clinically node negative, T1-2 tumours with sentinel lymph node biopsy positive in
≤ 2 lymph nodes without extra-capsular extension or matted nodes and undergoing
breast conserving surgery and tangential whole breast irradiation (* excludes
subjects treated with neo-adjuvant systemic therapy)

Definitive surgery and/or chemotherapy have been completed at least 4 weeks prior to
randomization. Surgical margins must be clear of invasive carcinoma. If there is
microscopic residual ductal in situ disease present at lumpectomy or total mastectomy
margins, further excision is highly recommended. If further excision is not undertaken,
the subject may still be entered on study, provided that in addition to breast or chest
wall irradiation, a boost to the tumour bed is delivered. In situ lobular disease at the
margin is acceptable.

Adjuvant subjects with the following pT pN combinations are eligible:

- pT1c, pN0 AND negative estrogen and progesterone receptors AND HER2 negative OR

- pT2N0 and at least one of the following tumour characteristics: histologic grade 3,
lymphovascular invasion, negative estrogen and progesterone receptors, HER2 positive,
Oncotype Dx recurrence score ≥ 25 (or if Oncotype Dx recurrence score is not
available, Ki67 > 14%) OR

- Subjects with pT3, pN0 OR

- Subjects with pT1-3, pN1-3

The eligibility of neo-adjuvant subjects is assessed on the basis of cTNM. The same
eligible TNM combinations apply.

- HER2 status must be known. (Positive = 3+ over-expression by IHC in > 30% of invasive
tumour cells OR HER2 gene amplification by FISH/CISH > 6 HER2 gene copies per
nucleus, OR a FISH/CISH ratio: HER2 gene copies to chromosome 17 signals of ≥ 2.2.
All other results will be considered negative).

- Patients must have had a bilateral mammogram within 12 months prior to randomization,
unless the initial surgery was a total mastectomy, in which case only a mammogram of
the remaining breast is required. (Subjects with bilateral total mastectomies and no
mammogram within 12 months prior to randomization must, instead, have a physical
examination of the chest wall to ensure there is no residual or recurrent disease at
the time of randomization. The date of this examination is used in place of the
mammogram date on the eligibility checklist.)

- Investigations, including chest X-ray or CT chest, bone scan (with radiographs of
suspicious areas) and abdominal ultrasound or liver scan or CT abdomen have been
performed between the first histologic diagnosis and the time of randomization.

- Chest X-Ray, 2 view (or Chest CT) is mandatory

- Bone scans (with x-rays of abnormal areas) are required only if there are signs
or symptoms of metastatic disease

- Abdominal imaging is required only if there are signs or symptoms of metastatic
disease

- Hematology investigations (WBC, Granulocytes, Platelets, Hemoglobin) have been
completed within 28 days prior to randomization and results are available.

- Biochemistry investigations have been completed within 28 days prior to randomization
and values are within the parameters required by the protocol.

AST < 1.8 X ULN; ALT < 1.8 X ULN; Alkaline Phosphatase < 2 X ULN; Serum Creatinine < 115
μmol/L (1.3mg/dL) Serum Bilirubin < institution ULN (except for subjects with Gilbert's
Disease who are eligible despite elevated serum bilirubin level)

- ECOG Performance Status of 0,1 or 2 (at baseline evaluation visit within 28 days
prior to randomization).

- Age ≥ 18 and < 75 and life expectancy of at least 5 years (18 years of age was used
as a cut-off due to the lack of data indicating that breast cancer is a health issue
in the < 18 years age group and metformin safety in pediatric patients has not been
confirmed. Age > 80 carries increased risk of lactic acidosis and study intervention
is for 5 years).

- Subjects must be accessible for treatment and follow-up. Investigators must assure
themselves the subjects randomized on this trial will be available for complete
documentation of the treatment, adverse events, and follow-up.

- In accordance with NCIC CTG policy, protocol treatment is to begin within 10 working
days of patient randomization.

- Subject consent must be obtained according to local Institutional and/or University
Human Experimentation Committee requirements. It will be the responsibility of the
local participating investigators to obtain the necessary local clearance, and to
indicate in writing to the NCIC CTG Study Coordinator that such clearance has been
obtained, before the trial can commence in that centre. Because of differing
requirements, a standard consent form for the trial will not be provided but a sample
form is given in Appendix XII. A copy of the initial full board REB approval and
approved consent form must be sent to the central office. The patient must sign the
consent form prior to randomization or registration. Please note that the consent
form for this study must contain a statement which gives permission for the NCIC CTG
and monitoring agencies to review patient records (see Section 16 for further
details).

For the first 888 eligible English or French-speaking subjects only (sub-set enrollment
completed 2011NOV04):

- Subject is able (i.e. sufficiently fluent) and willing to complete the Quality of
Life (EORTC QLQ C-30 and Trial Specific Checklist) in English or French. The baseline
assessment must already have been completed at the time of enrollment. Inability
(illiteracy in English or French, loss of sight or other equivalent reason) to
complete questionnaires will not make the patient ineligible for the study; however,
ability but unwillingness to complete the questionnaires will make the patient
ineligible. (Once the target number of 888 subjects is achieved, this criterion will
no longer need to be fulfilled.) [See Appendix VI]. Sub-set enrollment completed
2011NOV04.

- English-speaking subjects who have completed the Quality of Life Questionnaire who
are able (i.e. sufficiently fluent) and willing to complete Nurses Health Study II
Physical Activity Questionnaire and Block Alive Screener in English. The baseline
assessment must already have been completed at the time of enrollment. Inability
(illiteracy in English, loss of sight or other equivalent reason) to complete
questionnaires will not make the patient ineligible for the study; however, ability
but unwillingness to complete the questionnaires will make the patient ineligible.
(This component of the study will close at the same time as the Quality Of Life
sub-study.) Sub-set enrollment completed 2011NOV04.

Ineligibility Criteria:

- Subjects with a history of other malignancies, except: adequately treated
non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other
solid tumours curatively treated with no evidence of disease for ≥ 5 years.

- Subjects with locally recurrent or metastatic breast carcinoma. (Subjects with prior
invasive breast cancer at any time are not eligible. Subjects with prior DCIS only in
either breast are eligible provided the DCIS has been curatively treated including
surgery, radiotherapy and/or Tamoxifen).

- Subjects whose axillary node status is unknown.

- Known diabetes (type 1 or 2) or baseline fasting glucose > 7.0 mmol/L (126 mg/dL).
(Sampled and assayed according to local institution's procedures.)

- Known hypersensitivity or intolerance to metformin.

- Any condition associated with increased risk of metformin-associated lactic acidosis
(e.g. congestive heart failure defined as New York Heart Association {NYHA} Class III
or IV functional status [see Appendix IX], history of acidosis of any type; habitual
* Currently taking metformin, sulfonylureas, thiazolidinediones or insulin for any
reason.

- Current or planned pregnancy or lactation in women of child-bearing potential. Men
should not father a child. (An effective method of birth control should be used while
on study treatment which could include abstinence, IUD, condoms or other barrier
methods of birth control because the safety of metformin in pregnancy or in male
fertility has not been established).

- Concurrent or planned participation in randomized trials of weight loss or exercise
interventions or trials targeting insulin, IGF-1 or their receptors, or involving
P13K inhibitors (at the time of randomization)*.

- These interventions would interfere with the primary endpoint. (Also, in general,
double randomizations in breast cancer trials for MA.32 patients are permitted only
if the patient meets all the eligibility criteria for MA.32 and the sponsor of the
previous trial has no objection to the patient also being enrolled in MA.32).

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Invasive disease-free survival

Outcome Time Frame:

6 years

Safety Issue:

No

Principal Investigator

Pamela J. Goodwin, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mount Sinai Hospital, Toronto

Authority:

Canada: Health Canada

Study ID:

MA32

NCT ID:

NCT01101438

Start Date:

July 2010

Completion Date:

December 2016

Related Keywords:

  • Breast Cancer
  • stage I breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IIIC breast cancer
  • male breast cancer
  • estrogen receptor-negative breast cancer
  • HER2-negative breast cancer
  • progesterone receptor-negative breast cancer
  • estrogen receptor-positive breast cancer
  • HER2-positive breast cancer
  • progesterone receptor-positive breast cancer
  • Breast Neoplasms

Name

Location

Akron City HospitalAkron, Ohio  44304
Albert Einstein College of MedicineBronx, New York  10461
Johns Hopkins UniversityBaltimore, Maryland  21205
Suburban HospitalBethesda, Maryland  20814
Cleveland Clinic FoundationCleveland, Ohio  44195
Roswell Park Cancer InstituteBuffalo, New York  14263
Mayo ClinicRochester, Minnesota  55905
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
Medical University of South CarolinaCharleston, South Carolina  29425-0721
University of Washington Medical CenterSeattle, Washington  98195-6043
Rhode Island HospitalProvidence, Rhode Island  02903
Pennsylvania HospitalPhiladelphia, Pennsylvania  19107
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
United HospitalSt. Paul, Minnesota  55102
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Avera Cancer InstituteSioux Falls, South Dakota  57105
Loyola University Medical CenterMaywood, Illinois  60153
CentraCare ClinicSaint Cloud, Minnesota  56303
Rapid City Regional HospitalRapid City, South Dakota  57709
Marshfield ClinicMarshfield, Wisconsin  54449
Glendale Memorial Hospital and Health CenterGlendale, California  91204
Stanford UniversityStanford, California  94305
South Georgia Medical CenterValdosta, Georgia  31603
Ingalls Memorial HospitalHarvey, Illinois  60426
Mary Bird Perkins Cancer CenterBaton Rouge, Louisiana  70809
Beth Israel Medical CenterNew York, New York  10003
Akron General Medical CenterAkron, Ohio  44302
Martha Jefferson HospitalCharlottesville, Virginia  22901
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
North Shore University HospitalManhasset, New York  11030
Hartford HospitalHartford, Connecticut  06102-5037
Eastern Maine Medical CenterBangor, Maine  04401
Providence Alaska Medical CenterAnchorage, Alaska  99508
William Beaumont HospitalRoyal Oak, Michigan  48073
Kaiser Permanente Medical Center - Santa ClaraSanta Clara, California  95051-5386
John Muir Medical CenterWalnut Creek, California  94598
Maimonides Medical CenterBrooklyn, New York  11219
Group Health CooperativeSeattle, Washington  98112
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
MetroHealth Medical CenterCleveland, Ohio  44109
Central Baptist HospitalLexington, Kentucky  40503
Valley HospitalRidgewood, New Jersey  07450
Trinity Cancer Care CenterMinot, North Dakota  58701
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
Mount Sinai Medical CenterNew York, New York  10029
Montefiore Medical CenterBronx, New York  10467-2490
Mount Nittany Medical CenterState College, Pennsylvania  16803
Chester County HospitalWest Chester, Pennsylvania  19380
Sibley Memorial HospitalWashington, District of Columbia  20016
Munson Medical CenterTraverse City, Michigan  49684
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
Paoli Memorial HospitalPaoli, Pennsylvania  19301-1792
Rochester General HospitalRochester, New York  14621
Front Range Cancer SpecialistsFort Collins, Colorado  80528
Poudre Valley HospitalFort Collins, Colorado  80524
Swedish Covenant HospitalChicago, Illinois  60625
Bryn Mawr HospitalBryn Mawr, Pennsylvania  19010
Doctor's Hospital of LaredoLaredo, Texas  78041
Mountainview MedicalBerlin, Vermont  05602
North Star Lodge Cancer Center at Yakima Valley Memorial HospitalYakima, Washington  98902
Mercy HospitalCoon Rapids, Minnesota  55433
Trinity Medical CenterMoline, Illinois  61265-1291
Ottumwa Regional Health CenterOttumwa, Iowa  52501
Fairview-Southdale HospitalEdina, Minnesota  55435
Abbott-Northwestern HospitalMinneapolis, Minnesota  55407
Regions HospitalSaint Paul, Minnesota  55101
Rice Memorial HospitalWillmar, Minnesota  56201
Altru Cancer CenterGrand Forks, North Dakota  58206
Lancaster General HospitalLancaster, Pennsylvania  17604-3555
Pomona Valley Hospital Medical CenterPomona, California  91767
Northeast Georgia Medical CenterGainesville, Georgia  30501
Battle Creek Health SystemBattle Creek, Michigan  49017
Saint Luke's HospitalChesterfield, Missouri  63017
Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Wenatchee Valley Medical CenterWenatchee, Washington  98801-2028
Marshfield Clinic Cancer Care at Regional Cancer CenterEau Claire, Wisconsin  54701
Marshfield Clinic - Weston CenterWeston, Wisconsin  54476
Memorial Hospital of Rhode IslandPawtucket, Rhode Island  02860
Singing River HospitalPascagoula, Mississippi  39581
Lowell General HospitalLowell, Massachusetts  01854
AnMed Health Cancer CenterAnderson, South Carolina  29621
Presbyterian HospitalCharlotte, North Carolina  28233-3549
Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404
Mayo Clinic in FloridaJacksonville, Florida  32224
Washington Hospital CenterWashington, District of Columbia  20010
Memorial Medical CenterSpringfield, Illinois  62781
McLeod Regional Medical CenterFlorence, South Carolina  29501
Metro Health HospitalGrand Rapids, Michigan  49506
University of PittsburghPittsburgh, Pennsylvania  15261
Vanderbilt UniversityNashville, Tennessee  37232-6305
Lynchburg Hematology-Oncology ClinicLynchburg, Virginia  24501
Tahoe Forest Cancer CenterTruckee, California  96161
Elmhurst Memorial HospitalElmhurst, Illinois  60126
University of ConnecticutFarmington, Connecticut  06032
Case Western Reserve UniversityCleveland, Ohio  44106
High Point Regional HospitalHigh Point, North Carolina  27261
Yale UniversityNew Haven, Connecticut  06520
Wayne State UniversityDetroit, Michigan  48202
Ohio State University Medical CenterColumbus, Ohio  43210
New Hampshire Oncology-Hematology PAHooksett, New Hampshire  03106
University of Arizona Health Sciences CenterTucson, Arizona  85724
Albert Einstein Medical CenterPhiladelphia, Pennsylvania  19141
University of Texas Health Science CenterSan Antonio, Texas  78284
Dartmouth Hitchcock Medical CenterLebanon, New Hampshire  03756
Mid Dakota ClinicBismarck, North Dakota  58501
University of ChicagoChicago, Illinois  60637
University Of VermontBurlington,, Vermont  05403
Kaiser PermanenteSacramento, California  
Wichita CCOPWichita, Kansas  67214-3882
Virginia Mason CCOPSeattle, Washington  98101
Huntsman Cancer Institute/University of UtahSalt Lake City, Utah  84112
Mount Sinai Hospital Medical CenterChicago, Illinois  60608
Addison Gilbert HospitalGloucester, Massachusetts  01930
Columbia Saint Mary's Hospital - OzaukeeMequon, Wisconsin  53097
Metro-Minnesota CCOPSt. Louis Park, Minnesota  
University of New MexicoAlbuquerque, New Mexico  87131
Oregon Health and Science UniversityPortland, Oregon  97201
Decatur Memorial HospitalDecatur, Illinois  62526
Georgetown University HospitalWashington, District of Columbia  20007
Mercy Medical CenterBaltimore, Maryland  21202
Kaiser PermanentePortland, Oregon  97227
Frederick Memorial HospitalFrederick, Maryland  21701
Lankenau HospitalWynnewood, Pennsylvania  19096
Florida HospitalOrlando, Florida  32803
Phoenixville HospitalPhoenixville, Pennsylvania  19460
University of Southern CaliforniaLos Angeles, California  90033
Rockwood ClinicSpokane, Washington  99220
Moffitt Cancer Center and Research InstituteTampa, Florida  33612
Penn State Milton S Hershey Medical CenterHershey, Pennsylvania  17033
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Kaiser Permanente, HaywardHayward, California  94545
Fremont - Rideout Cancer CenterMarysville, California  95901
Bay Area Tumor Institution CCOPOakland, California  94609
Kaiser Permanente-OaklandOakland, California  94611
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
University of California San Francisco Medical Center-Mount ZionSan 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
Memorial Hospital Colorado SpringsColorado Springs, Colorado  80909
Stamford HospitalStamford, Connecticut  06904
The Watson ClinicLakeland, Florida  33805
Phoebe Putney Memorial HospitalAlbany, Georgia  31703
University of HawaiiHonolulu, Hawaii  96813
Rush - Copley Medical CenterAurora, Illinois  60504
John H Stroger Jr Hospital of Cook CountyChicago, Illinois  60612-3785
Resurrection HealthcareChicago, Illinois  60631
Saint Francis HospitalEvanston, Illinois  60202
Evanston CCOP-NorthShore University HealthSystemEvanston, Illinois  60201
Illinois Oncology Research Association CCOPPeoria, Illinois  61615
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Howard Regional Healthcare SystemKokomo, Indiana  46904
Saint Anthony Memorial Health CenterMichigan City, Indiana  46360
McFarland ClinicAmes, Iowa  50010
Grand Rapids Clinical Oncology ProgramGrand Rapids, Michigan  49503
Saint Mary's Health CareGrand Rapids, Michigan  49503
Spectrum Health at Butterworth CampusGrand Rapids, Michigan  49503
Mercy Health Partners-Mercy CampusMuskegon, Michigan  49443
Duluth Clinic CCOPDuluth, Minnesota  55805
Unity HospitalFridley, Minnesota  55432
Saint John's Hospital - HealtheastMaplewood, Minnesota  55109
Minnesota Oncology Hematology PA-MaplewoodMaplewood, Minnesota  55109
North Memorial Medical Health CenterRobbinsdale, Minnesota  55422
Park Nicollet Clinic - Saint Louis ParkSaint Louis Park, Minnesota  55416
Minnesota Oncology and Hematology PA-WoodburyWoodbury, Minnesota  55125
Saint Louis-Cape Girardeau CCOPSaint Louis, Missouri  63141
Missouri Baptist Medical CenterSaint Louis, Missouri  63131
Saint John's Mercy Medical CenterSaint Louis, Missouri  63141
Saint John's HospitalSpringfield, Missouri  65804
Cox Medical CenterSpringfield, Missouri  65807
Good Samaritan HospitalKearney, Nebraska  68847
Lincoln Medical Education Foundation Cancer Resource CenterLincoln, Nebraska  68510
Missouri Valley Cancer Consortium CCOPOmaha, Nebraska  68106
New Hampshire Oncology Hematology AssociatesHooksett, New Hampshire  03106
LRGHealthcare-Lakes Region General HospitalLaconia, New Hampshire  03246
Saint Barnabas Medical CenterLivingston, New Jersey  07039
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington CountyMount Holly, New Jersey  08060
Presbyterian Kaseman HospitalAlbuquerque, New Mexico  87110
The North Division of Montefiore Medical CenterBronx, New York  10466
New York University Langone Medical CenterNew York, New York  10016
Saint Luke's Roosevelt Hospital Center - Saint Luke's DivisionNew York, New York  10025
Columbia University Medical CenterNew York, New York  10032
State University of New York Upstate Medical UniversitySyracuse, New York  13210
Mission Hospitals IncAsheville, North Carolina  28801
Wayne Memorial HospitalGoldsboro, North Carolina  27534
Margaret R Pardee Memorial HospitalHendersonville, North Carolina  28791
Kinston Medical Specialists PAKinston, North Carolina  28501
Medcenter One Health SystemsBismarck, North Dakota  58501
Aultman Health FoundationCanton, Ohio  44710
Kettering Medical CenterKettering, Ohio  45429
Legacy Good Samaritan Hospital and Medical CenterPortland, Oregon  97210
Columbia River Oncology ProgramPortland, Oregon  97225
Saint Joseph Medical CenterReading, Pennsylvania  19605
Swedish Medical Center-First HillSeattle, Washington  98122-4307
Northwest CCOPTacoma, Washington  98405
Edwards Comprehensive Cancer CenterHuntington, West Virginia  25701
West Virginia UniversityMorgantown, West Virginia  26506
Wheeling HospitalWheeling, West Virginia  26003
Central Wisconsin Cancer ProgramFond Du Lac, Wisconsin  54935
Saint Vincent HospitalGreen Bay, Wisconsin  54301
Aurora BayCare Medical CenterGreen Bay, Wisconsin  54311-6519
Marshfield Clinic-Minocqua CenterMinocqua, Wisconsin  54548
University of California Medical Center At Irvine-Orange CampusOrange, California  92868
Women and Infants HospitalProvidence, Rhode Island  02905
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
Stony Brook University Medical CenterStony Brook, New York  11794
York HospitalYork, Maine  03909
Lahey Clinic Medical CenterBurlington, Massachusetts  01805
Elkhart ClinicElkhart, Indiana  46515
Moores University of California San Diego Cancer CenterLA Jolla, California  92093
University of Colorado Cancer Center - Anschutz Cancer PavilionAurora, Colorado  80045
Mount Sinai Medical Center CCOPMiami Beach, Florida  33140
Michiana Hematology Oncology PC-ElkhartElkhart, Indiana  46514
Michiana Hematology Oncology PC-PlymouthPlymouth, Indiana  46563
Michiana Hematology Oncology PC-South BendSouth Bend, Indiana  46601
Michiana Hematology Oncology-PC WestvilleWestville, Indiana  46391
Saint Vincent Hospital - Fallon ClinicWorcesster, Massachusetts  01608
Michiana Hematology Oncology PC-NilesNiles, Michigan  49120
Rex Cancer CenterRaleigh, North Carolina  27607
University of Tennessee - KnoxvilleKnoxville, Tennessee  37920
Wheaton Franciscan Healthcare - Saint JosephMilwaukee, Wisconsin  53210
Aurora Medical Center in SummitSummit, Wisconsin  53066
North Shore University Hospital CCOPManhasset, New York  11030
University of California at Los Angeles (UCLA )Los Angeles, California  90095
State University of New York Downstate Medical CenterBrooklyn, New York  11203
Monter Cancer CenterLake Success, New York  11042
Long Beach Memorial Medical Center-Todd Cancer InstituteLong Beach, California  90806
FirstHealth of the Carolinas-Moore Regional HosiptalPinehurst, North Carolina  28374
Arizona Cancer Center at University Medical Center NorthTucson, Arizona  85719
Vanderbilt Breast Center at One Hundred OaksNashville, Tennessee  37204
Kaiser Permanente-Deer Valley Medical CenterAntioch, California  94531
Kaiser Permanente Medical Center-VacavilleVacaville, California  95688
Greenwich HospitalGreenwich, Connecticut  06830
Connecticut Oncology and Hematology LLPTorrington, Connecticut  06790
Kaiser Permanente Moanalua Medical CenterHonolulu, Hawaii  96819
Kansas City CCOPPrairie Village, Kansas  66208
Owensboro Mercy Medical CenterOwensboro, Kentucky  42303
Coney Island HospitalBrooklyn, New York  11235
Forsyth Memorial HospitalWinston-Salem, North Carolina  27103
Pacific Medical Center-First HillSeattle, Washington  98104
Columbia Saint Mary's Water Tower Medical CommonsMilwaukee, Wisconsin  53211
Fairbanks Memorial HospitalFairbanks, Alaska  99701
Heartland Oncology and Hematology LLPCouncil Bluffs, Iowa  51503
Kaiser Permanente-FranklinDenver, Colorado  80205
Siouxland Hematology Oncology AssociatesSioux City, Iowa  51101
Kaiser Permanente-MissionSan Diego, California  92108
University Medical Center BrackenridgeAustin, Texas  78701
Providence Saint Mary Regional Cancer CenterWalla Walla, Washington  99362
Sanford ClinicSioux Falls, South Dakota  57104
Mount Kisco Medical GroupMt. Kisco, New York  10549
Pinnacle Oncology AssociatesScottsdale, Arizona  85258
Alta Bates Summit Medical Center-Herrick CampusBerkeley, California  94704
Enloe Medical CenterChico, California  95926
University of California Davis-Cancer CenterSacramento, California  95817
Boca Raton Regional HospitalBoca Raton, Florida  33486
Carle Foundation - Carle Cancer CenterUrbana, Illinois  61801
Indiana University Hospital/Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202
Michiana Hematology Oncology PC-MishawakaMishawaka, Indiana  46545-1470
Oncology Associates at Mercy Medical CenterCedar Rapids, Iowa  52403
University of Michigan Health System-Cancer CenterAnn Arbor, Michigan  48109
Marie Yeager Cancer CenterSaint Joseph, Michigan  49085
The Dana-Farber Cancer Institute at LondonderryLondonderry, New Hampshire  03053
Hematology Oncology Associates of Central New York PCEast Syracuse, New York  13057
Mount Kisco Medical Group at Northern Westchester HospitalMount Kisco, New York  10549-3417
Sanford Clinic North-FargoFargo, North Dakota  58102
Sanford Medical Center-FargoFargo, North Dakota  58122
Saint John Medical CenterLongview, Washington  98632
Gundersen Lutheran Health System/CCOPLa Crosse, Wisconsin  54601