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A Randomized Phase III Trial of Neoadjuvant Therapy in Patients With Palpable and Operable Breast Cancer Evaluating the Effect on Pathologic Complete Response (pCR) of Adding Capecitabine or Gemcitabine to Docetaxel When Administered Before AC With or Without Bevacizumab and Correlative Science Studies Attempting to Identify Predictors of High Likelihood for pCR With Each of the Regimens


Phase 3
18 Years
N/A
Open (Enrolling)
Female
Breast Cancer

Thank you

Trial Information

A Randomized Phase III Trial of Neoadjuvant Therapy in Patients With Palpable and Operable Breast Cancer Evaluating the Effect on Pathologic Complete Response (pCR) of Adding Capecitabine or Gemcitabine to Docetaxel When Administered Before AC With or Without Bevacizumab and Correlative Science Studies Attempting to Identify Predictors of High Likelihood for pCR With Each of the Regimens


OBJECTIVES:

Primary

- Compare the efficacy of docetaxel followed by doxorubicin hydrocloride and
cyclophosphamide (AC) vs docetaxel and capecitabine followed by AC vs docetaxel and
gemcitabine hydrochloride followed by AC, with or without bevacizumab, in terms of an
increase in the rate of pathologic complete response (pCR) in the breast, in women with
palpable or operable breast cancer.

Secondary

- Compare docetaxel/capecitabine with AC vs docetaxel/gemcitabine hydrochloride with AC
vs docetaxel with AC, with or without bevacizumab, in terms of the rate of pCR in the
breast and all post-therapy lymph nodes evaluated histologically (pCR breast and
nodes).

- Determine whether the addition of bevacizumab to the docetaxel/anthracycline-based
regimens (docetaxel with AC, docetaxel and capecitabine with AC, and docetaxel and
gemcitabine hydrochloride with AC) will increase the rate of pCR of the breast and
nodes compared to the same docetaxel/anthracycline-based regimens without bevacizumab
in these patients.

- Determine whether the addition of capecitabine or gemcitabine hydrochloride to
docetaxel, with or without bevacizumab, will increase the rate of clinical overall
response (cOR) compared to docetaxel alone with or without bevacizumab in these
patients.

- Determine whether the addition of bevacizumab to the docetaxel/anthracycline-based
regimens will increase the rate of cOR compared to the same
docetaxel/anthracycline-based regimens without bevacizumab in these patients.

- Determine whether the addition of capecitabine or gemcitabine hydrochloride to
docetaxel, with or without bevacizumab, will increase the rate of clinical complete
response (cCR) compared to docetaxel alone with or without bevacizumab in these
patients.

- Determine whether the addition of bevacizumab to the docetaxel/anthracycline-based
regimens (docetaxel with AC, docetaxel/capecitabine with AC, and docetaxel/gemcitabine
hydrochloride with AC) will increase the rate of cCR compared to the same
docetaxel/anthracycline-based regimens without bevacizumab in these patients.

- Identify gene expression profiles that can predict pCR in patients treated with the
different sequential docetaxel/anthracycline-based regimens with or without
bevacizumab.

- Identify gene expression profiles that can predict cOR in patients treated with
docetaxel alone, docetaxel/capecitabine, or docetaxel/gemcitabine hydrochloride with or
without bevacizumab.

- Determine the accuracy of an in vitro chemoresponse assay (ChemoFx®) as a predictor of
pCR in patients treated with the different sequential docetaxel/anthracycline-based
regimens without bevacizumab.

- Determine the accuracy of ChemoFx® as a predictor of cOR in patients treated with
docetaxel alone, docetaxel/capecitabine, or docetaxel/gemcitabine hydrochloride without
bevacizumab in these patients.

- Determine the impact of preoperative bevacizumab and sequential chemotherapy regimens
and postoperative bevacizumab therapy on cardiac function in these patients.

- Determine the impact of bevacizumab on surgical complications in these patients.

- Determine the toxicity of the preoperative regimens and the toxicity of postoperative
bevacizumab in these patients.

- Compare the docetaxel/anthracycline-based regimens with vs without bevacizumab, in
terms of an increase in disease-free survival, of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor
size (2-4 cm vs > 4 cm), nodal status (negative vs positive), hormone receptor status
(estrogen receptor [ER]-positive and/or progesterone-receptor [PgR]-positive vs ER- and
PgR-negative), and age (< 50 years vs ≥ 50 years). Patients are randomized to 1 of 6
treatment arms.

Core needle biopsies are performed at baseline. Tumor tissue samples are also collected
during definitive surgery. Samples are examined for gene expression and polymorphism by
reverse transcriptase-polymerase chain reaction analysis and chemoresponse assay (ChemoFx®).

After completion of study therapy, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 1,200 patients will be accrued for this study.


Inclusion Criteria:



- The patient must have consented to participate and must have signed and dated an
appropriate Institutional Review Board (IRB)-approved consent form that conforms to
federal and institutional guidelines for the study treatment and submission of
pre-entry core biopsy material for correlative studies.

- Patients must be female.

- Patients must be 18 years of age or older.

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 or 1.

- The diagnosis of invasive adenocarcinoma of the breast must have been made by core
needle biopsy.

- The primary breast tumor must be palpable and measure greater than or equal to 2.0 cm
on physical exam.

- All patients must have their left ventricular ejection fraction (LVEF) assessed by
multigated acquisition (MUGA) scan or echocardiogram within 3 months prior to study
entry. The LVEF must be greater than or equal to the lower limit of normal (LLN) for
the cardiac imaging facility performing the study. Note: If the cardiac imaging
facility cannot provide a LLN, use 50% as the LLN value.

- Note: Since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF
assessments to determine if bevacizumab therapy can be continued, it is critical that
this baseline study be an accurate assessment of the patient's LVEF. If the baseline
LVEF is greater than 75%, the investigator should have the study reviewed for
accuracy prior to study entry. Following study entry, the LVEF determination may be
reviewed up until the time of the post-chemotherapy (preoperative) evaluation.
Please note that if a more accurate value is obtained from the review of the baseline
MUGA or echocardiogram, the correct value must be submitted to the NSABP before the
post-chemotherapy (preoperative) MUGA or echocardiogram is performed or it cannot be
used for managing postoperative bevacizumab.

- All patients must have an EKG within 3 months prior to study entry.

- At the time of randomization:

- Absolute neutrophil count (ANC) must be greater than or equal to 1200/mm3.

- Platelet count must be greater than or equal to 100,000/mm3.

- Hemoglobin must be greater than or equal to 10 g/dL.

- There must be evidence of adequate hepatic function by these criteria:

- Total bilirubin must be less than or equal to the ULN for the lab unless the
patient has a grade 1 bilirubin elevation (greater than ULN to 1.5 x ULN)
resulting from Gilbert's disease or similar syndrome due to slow conjugation of
bilirubin; and

- Alkaline phosphatase must be less than or equal 2.5 x ULN for the lab; and

- Aspartate Aminotransferase (AST) must be less than or equal to 1.5 x ULN for the
lab.

- Alkaline phosphatase and AST may not both be greater than the ULN. For example,
if the alkaline phosphatase is greater than the ULN but less than or equal 2.5 x
ULN, then the AST must be less than or equal the ULN. If the AST is greater
than the ULN but less than or equal 1.5 x ULN, then the alkaline phosphatase
must be less than or equal ULN.

- Patients with either skeletal pain or alkaline phosphatase that is greater than ULN
but less than or equal 2.5 x ULN are eligible for inclusion in the study if bone
scans do not demonstrate metastatic disease. Suspicious findings on bone scan must
be confirmed as benign by x-ray, MRI, or biopsy.

- Patients with AST or alkaline phosphatase greater than ULN are eligible for inclusion
in the study if liver imaging does not demonstrate metastatic disease and adequate
bone marrow and liver function results as described above are met.

- The following criteria for evidence of adequate renal function must be met:

- Serum creatinine less than or equal ULN for the lab.

- Calculated creatinine clearance must be greater than 50 mL/min.

- Urine protein/urine creatinine (UPC) ratio must be less than 1.0.

- Patient must be able to swallow oral medications.

Exclusion criteria:

- Tumor determined to be strongly human epidermal growth factor receptor 2
(HER2)-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization
(positive for gene amplification).

- Excisional or incisional biopsy for this primary breast tumor.

- Surgical axillary staging procedure prior to study entry. Exceptions: 1) Fine
Needle Aspiration (FNA) or core biopsy of an axillary node is permitted for any
patient, and 2) although not recommended, a pre-neoadjuvant therapy sentinel lymph
node biopsy for patients with clinically negative axillary nodes is permitted.

- Tumors clinically staged as T4.

- Ipsilateral cN2b or cN3 disease. (Patients with cN1 or cN2a disease are eligible.)

- Definitive clinical or radiologic evidence of metastatic disease.

- Synchronous bilateral breast cancer (invasive or DCIS).

- Treatment including radiation therapy, chemotherapy, biotherapy, and/or hormonal
therapy for the currently diagnosed breast cancer prior to study entry.

- Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement
therapy, etc. (These patients are eligible if this therapy is discontinued prior to
randomization.)

- Therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective
estrogen receptor modulator (SERM), either for osteoporosis or breast cancer
prevention. (Patients are eligible only if these medications are discontinued prior
to randomization.)

- Prior history of breast cancer, including DCIS. (Patients with a history of lobular
carcinoma in situ [LCIS] are eligible.)

- Prior therapy with anthracyclines, taxanes, capecitabine, 5-FU, gemcitabine, or
bevacizumab for any malignancy.

- Other malignancies unless the patient is considered to be disease-free for 5 or more
years prior to randomization and is deemed by her physician to be at low risk for
recurrence. Patients with the following cancers are eligible if diagnosed and
treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ
of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the
skin.

- Cardiac disease that would preclude the use of anthracyclines. This includes:

- angina pectoris that requires the use of anti-anginal medication;

- history of documented congestive heart failure;

- serious cardiac arrhythmia requiring medication;

- severe conduction abnormality;

- valvular disease with documented cardiac function compromise; and

- uncontrolled hypertension defined as BP greater than 150/90 on antihypertensive
therapy. (Patients with hypertension that is well controlled on medication are
eligible.)

- History of myocardial infarction documented by elevated cardiac enzymes or persistent
regional wall abnormalities on assessment of LV function.

- History of transient ischemic attack (TIA) or cerebrovascular accident (CVA).

- History of other arterial thrombotic event within 12 months before study entry.

- Symptomatic peripheral vascular disease.

- Any significant non-traumatic bleeding within 6 months before study entry.

- Serious or non-healing wound, skin ulcers, or incompletely healed bone fracture.

- Gastroduodenal ulcer(s) determined by endoscopy to be active.

- Invasive procedures defined as follows:

- Major surgical procedure, open biopsy, or significant traumatic injury within 28
days prior to planned start of study therapy. (Note: Placement of a vascular
access device is not considered a major surgical procedure.)

- Anticipation of need for major surgical procedures (other than the required
breast surgery) during the course of the study.

- Known bleeding diathesis or coagulopathy. (Patients on warfarin with an in-range
international normalized ration [INR] [usually between 2 and 3] are eligible.)

- Sensory/motor neuropathy greater than or equal grade 2, as defined by the NCI's
Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v3.0).

- Other non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that
would preclude treatment with any of the treatment regimens or would prevent required
follow-up.

- Conditions that would prohibit administration of corticosteroids.

- History of severe hypersensitivity reaction to drugs formulated with polysorbate 80.

- Administration of any investigational agents within 30 days before study entry.

- Pregnancy or lactation at the time of proposed randomization.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Pathologic complete response (pCR) of the primary tumor in the breast

Outcome Description:

No histologic evidence of invasive tumor cells in the breast specimen removed at surgery

Outcome Time Frame:

Time of surgery, on average 6 or 13 months

Safety Issue:

No

Principal Investigator

Norman Wolmark, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NSABP Foundation, Inc.

Authority:

United States: Food and Drug Administration

Study ID:

NSABP B-40

NCT ID:

NCT00408408

Start Date:

November 2006

Completion Date:

March 2016

Related Keywords:

  • Breast Cancer
  • stage I breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • Breast Neoplasms

Name

Location

Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
CCOP - Upstate CarolinaSpartanburg, South Carolina  29303
CCOP - WichitaWichita, Kansas  67214-3882
Hurley Medical CenterFlint, Michigan  48503
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
CCOP - Kansas CityKansas City, Missouri  64131
CCOP - Missouri Valley Cancer ConsortiumOmaha, Nebraska  68131
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Mount Sinai Medical CenterMiami Beach, Florida  33140
CCOP - Illinois Oncology Research AssociationPeoria, Illinois  61602
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Aurora Presbyterian HospitalAurora, Colorado  80012
Boulder Community HospitalBoulder, Colorado  80301-9019
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
CCOP - Colorado Cancer Research ProgramDenver, Colorado  80224-2522
Porter Adventist HospitalDenver, Colorado  80210
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
St. Joseph HospitalDenver, Colorado  80218
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical CenterGrand Junction, Colorado  81502
Sky Ridge Medical CenterLone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United HospitalLongmont, Colorado  80502
St. Mary - Corwin Regional Medical CenterPueblo, Colorado  81004
North Suburban Medical CenterThornton, Colorado  80229
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health CenterFarmington, Connecticut  06360-2875
CCOP - Michigan Cancer Research ConsortiumAnn Arbor, Michigan  48106
Saint Joseph Mercy Cancer CenterAnn Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical CenterDearborn, Michigan  48123-2500
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Sparrow Regional Cancer CenterLansing, Michigan  48912-1811
St. John Macomb HospitalWarren, Michigan  48093
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Duluth Clinic Cancer Center - DuluthDuluth, Minnesota  55805-1983
CCOP - DuluthDuluth, Minnesota  55805
Miller - Dwan Medical CenterDuluth, Minnesota  55805
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
Aultman Cancer Center at Aultman HospitalCanton, Ohio  44710-1799
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
Penn State Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Geisinger Medical Group - Scenery ParkState College, Pennsylvania  16801
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical CenterWilkes-Barre, Pennsylvania  18711
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Medical X-Ray Center, PCSioux Falls, South Dakota  57105
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Medical College of Wisconsin Cancer CenterMilwaukee, Wisconsin  53226
Marshfield Clinic - Indianhead CenterRice Lake, Wisconsin  54868
CCOP - OchsnerNew Orleans, Louisiana  70121
CCOP - Bay Area Tumor InstituteOakland, California  94609-3305
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Memorial Hospital of South BendSouth Bend, Indiana  46601
CCOP - Cancer Research for the OzarksSpringfield, Missouri  65807
CCOP - Montana Cancer ConsortiumBillings, Montana  59101
Newark Beth Israel Medical CenterNewark, New Jersey  07112
CCOP - DaytonKettering, Ohio  45429
CCOP - GreenvilleGreenville, South Carolina  29615
LDS HospitalSalt Lake City, Utah  84143
Rush University Medical CenterChicago, Illinois  60612-3824
CCOP - Northern Indiana CR ConsortiumSouth Bend, Indiana  46601
Saint Joseph Regional Medical CenterSouth Bend, Indiana  46617
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbia, Missouri  65203
MultiCare Regional Cancer Center at Tacoma General HospitalTacoma, Washington  98405
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
MBCCOP - LSU Health Sciences CenterNew Orleans, Louisiana  70112
CCOP - St. Louis-Cape GirardeauSaint Louis, Missouri  63141
CCOP - NorthwestTacoma, Washington  98405-0986
Kaiser Permanente Medical Center - VallejoVallejo, California  94589
Utah Valley Regional Medical Center - ProvoProvo, Utah  84604
Peninsula Regional Medical CenterSalisbury, Maryland  21801
Wesley Medical CenterWichita, Kansas  67214
Fletcher Allen Health Care - University Health Center CampusBurlington, Vermont  05401
Kaiser Permanente Medical Center - San Francisco Geary CampusSan Francisco, California  94115
St. Vincent Mercy Medical CenterToledo, Ohio  43608
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Josephine Ford Cancer Center at Henry Ford HospitalDetroit, Michigan  48202
Thompson Cancer Survival CenterKnoxville, Tennessee  37916
James Graham Brown Cancer Center at University of LouisvilleLouisville, Kentucky  40202
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Hulston Cancer Center at Cox Medical Center SouthSpringfield, Missouri  65807
St. John's Regional Health CenterSpringfield, Missouri  65804
McDowell Cancer Center at Akron General Medical CenterAkron, Ohio  44307
Cancer Institute of New Jersey at HamiltonHamilton, New Jersey  08690
CCOP - Toledo Community HospitalToledo, Ohio  43623-3456
Loma Linda University Cancer Institute at Loma Linda University Medical CenterLoma Linda, California  92354
Kaiser Permanente Medical Center - OaklandSacramento, California  95825
Broward General Medical Center Cancer CenterFt. Lauderdale, Florida  33316
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
St. Vincent Indianapolis HospitalIndianapolis, Indiana  46260
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
Ochsner Cancer Institute at Ochsner Clinic FoundationNew Orleans, Louisiana  70121
Breslin Cancer Center at Ingham Regional Medical CenterLansing, Michigan  48910
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Medical University of Ohio Cancer CenterToledo, Ohio  43614
Toledo HospitalToledo, Ohio  43606
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Mary Babb Randolph Cancer Center at West Virginia University HospitalsMorgantown, West Virginia  26506
Our Lady of Mercy Medical Center Comprehensive Cancer CenterBronx, New York  10466
Mount Nittany Medical CenterState College, Pennsylvania  16803
Sibley Memorial HospitalWashington, District of Columbia  20016
Batte Cancer Center at Northeast Medical CenterConcord, North Carolina  28025
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Baptist Cancer Institute - JacksonvilleJacksonville, Florida  32207
Saint Anthony's Hospital at Saint Anthony's Health CenterAlton, Illinois  62002
Good Samaritan Regional Health CenterMt. Vernon, Illinois  62864
Southwest Medical CenterLiberal, Kansas  67901
David C. Pratt Cancer Center at St. John's MercySt. Louis, Missouri  63141
Northern Rockies Radiation Oncology CenterBillings, Montana  59101
Hematology-Oncology Centers of the Northern Rockies - BillingsBillings, Montana  59101
Big Sky OncologyGreat Falls, Montana  59405
St. Peter's HospitalHelena, Montana  59601
Kalispell Regional Medical CenterKalispell, Montana  59901
Glacier Oncology, PLLCKalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences CenterMissoula, Montana  59802
Montana Cancer Specialists at Montana Cancer CenterMissoula, Montana  59802
Community Medical CenterMissoula, Montana  59801
Wayne Memorial Hospital, IncorporatedGoldsboro, North Carolina  27534
American Fork HospitalAmerican Fork, Utah  84003
Utah Cancer Specialists at UCS Cancer CenterSalt Lake City, Utah  84106
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
Kaiser Permanente Medical Center - Santa Clara Kiely CampusSanta Clara, California  95051-5386
M.D. Anderson Cancer Center at OrlandoOrlando, Florida  32806
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical CenterSavannah, Georgia  31403-3089
Swedish-American Regional Cancer CenterRockford, Illinois  61104-2315
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Virginia Commonwealth University Massey Cancer CenterRichmond, Virginia  23298-0037
West Virginia University Health Sciences Center - CharlestonCharleston, West Virginia  25302
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
Kaiser Permanente Medical Center - SacramentoSacramento, California  95825
Huntsman Cancer Institute at University of UtahSalt Lake City, Utah  84112
Decatur Memorial Hospital Cancer Care InstituteDecatur, Illinois  62526
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
Helen and Harry Gray Cancer Center at Hartford HospitalHartford, Connecticut  06102-5037
Elkhart General HospitalElkhart, Indiana  46515
Howard Community HospitalKokomo, Indiana  46904
South Bend ClinicSouth Bend, Indiana  46617
Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital CenterBaltimore, Maryland  21237
Lakeland Regional Cancer Care Center - St. JosephSt. Joseph, Michigan  49085
Hope A Women's Cancer CenterAsheville, North Carolina  28801
Morgan Cancer Center at Lehigh Valley Hospital - Cedar CrestAllentown, Pennsylvania  18105
UPMC Cancer CentersPittsburgh, Pennsylvania  15232
Eden Medical CenterCastro Valley, California  94546
Kaiser Permanente - FremontFremont, California  94538
Kaiser Permanente Medical Center - HaywardHayward, California  94545
Alta Bates Summit Medical Center - Summit CampusOakland, California  94609
Valley Care Medical CenterPleasanton, California  94588
Kaiser Permanente Medical Center - Redwood CityRedwood City, California  94063
Kaiser Permanente Medical Center - RichmondRichmond, California  94801
Kaiser Permanente Medical Center - RosevilleRoseville, California  95661
South Sacramento Kaiser-Permanente Medical CenterSacramento, California  95823
Salinas Valley Memorial HospitalSalinas, California  93901
Kaiser Permanente Medical Office -Vandever Medical OfficeSan Diego, California  92120
Kaiser Permanente Medical Center - Santa TeresaSan Jose, California  95119
Kaiser Foundation Hospital - San RafaelSan Rafael, California  94903
Kaiser Permanente Medical Center - Santa RosaSanta Rosa, California  95403
Kaiser Permanente Medical Center - South San FranciscoSouth San Francisco, California  94080
Kaiser Permanente Medical Facility - StocktonStockton, California  95210
Kaiser Permanente Medical Center - Walnut CreekWalnut Creek, California  94596
Ella Milbank Foshay Cancer Center at Jupiter Medical CenterJupiter, Florida  33458
St. Joseph Medical CenterBloomington, Illinois  61701
Graham HospitalCanton, Illinois  61520
Memorial HospitalCarthage, Illinois  62321
Eureka Community HospitalEureka, Illinois  61530
Galesburg Cottage HospitalGalesburg, Illinois  61401
Mason District HospitalHavana, Illinois  62644
McDonough District HospitalMacomb, Illinois  61455
Edward Hospital Cancer CenterNaperville, Illinois  60540
BroMenn Regional Medical CenterNormal, Illinois  61761
Community Cancer CenterNormal, Illinois  61761
Community Hospital of OttawaOttawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - OttawaOttawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - PeoriaPeoria, Illinois  61615
OSF St. Francis Medical CenterPeoria, Illinois  61637
Proctor HospitalPeoria, Illinois  61614
Illinois Valley Community HospitalPeru, Illinois  61354
Perry Memorial HospitalPrinceton, Illinois  61356
St. Francis Hospital and Health Centers - Beech Grove CampusBeech Grove, Indiana  46107
Fort Wayne Medical Oncology and HematologyFort Wayne, Indiana  46815
Center for Cancer Therapy at LaPorte Hospital and Health ServicesLa Porte, Indiana  46350
Cancer Center of Kansas, PA - Dodge CityDodge City, Kansas  67801
Mary Bird Perkins Cancer Center - Baton RougeBaton Rouge, Louisiana  70809
Medical Center of Louisiana - New OrleansNew Orleans, Louisiana  70112
Hickman Cancer Center at Bixby Medical CenterAdrian, Michigan  49221
Community Cancer Center of MonroeMonroe, Michigan  48162
Providence Cancer Institute at Providence Hospital - Southfield CampusSouthfield, Michigan  48075
Saint Francis Medical CenterCape Girardeau, Missouri  63701
Immanuel Medical CenterOmaha, Nebraska  68122
Creighton University Medical CenterOmaha, Nebraska  68131-2197
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Charles R. Wood Cancer Center at Glens Falls HospitalGlens Falls, New York  12801
Iredell Memorial HospitalStatesville, North Carolina  28677
Forsyth Regional Cancer Center at Forsyth Medical CenterWinston-Salem, North Carolina  27103
Wood County Oncology CenterBowling Green, Ohio  43402
Samaritan North Cancer Care CenterDayton, Ohio  45415
Grandview HospitalDayton, Ohio  45405
David L. Rike Cancer Center at Miami Valley HospitalDayton, Ohio  45409
Good Samaritan HospitalDayton, Ohio  45406
Blanchard Valley Medical AssociatesFindlay, Ohio  45840
Charles F. Kettering Memorial HospitalKettering, Ohio  45429
Lima Memorial HospitalLima, Ohio  45804
St. Luke's HospitalMaumee, Ohio  43537
Northwest Ohio Oncology CenterMaumee, Ohio  43537
Middletown Regional HospitalMiddletown, Ohio  45044
Toledo Clinic - OregonOregon, Ohio  43616
St. Charles Mercy HospitalOregon, Ohio  43616
North Coast Cancer Care, IncorporatedSandusky, Ohio  44870
Mercy Hospital of TiffinTiffin, Ohio  44883
Toledo Clinic, Incorporated - Main ClinicToledo, Ohio  43623
UVMC Cancer Care Center at Upper Valley Medical CenterTroy, Ohio  45373-1300
Fulton County Health CenterWauseon, Ohio  43567
Ruth G. McMillan Cancer Center at Greene Memorial HospitalXenia, Ohio  45385
Kaiser Permanente Health Care - PortlandPortland, Oregon  97232
Bryn Mawr HospitalBryn Mawr, Pennsylvania  19010
Lankenau Cancer Center at Lankenau HospitalWynnewood, Pennsylvania  19096
Doctor's Hospital of LaredoLaredo, Texas  78041
Dixie Regional Medical Center - East CampusSaint George, Utah  84770
Mountainview MedicalBerlin, Vermont  05602
Welch Cancer Center at Sheridan Memorial HospitalSheridan, Wyoming  82801
St. Anthony Central HospitalDenver, Colorado  80204-1335
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
St. Francis HospitalFederal Way, Washington  98003
St. Clare HospitalLakewood, Washington  98499-0998
Providence St. Peter Hospital Regional Cancer CenterOlympia, Washington  98506
Good Samaritan Cancer CenterPuyallup, Washington  98371
Allenmore HospitalTacoma, Washington  98411-0414
Highland General HospitalOakland, California  94602
Northeast Georgia Medical CenterGainesville, Georgia  30501
Great Lakes Cancer Institute at McLaren Regional Medical CenterFlint, Michigan  48532
Cancer Resource Center - LincolnLincoln, Nebraska  68510
Randolph HospitalAsheboro, North Carolina  27203
Moses Cone Regional Cancer Center at Wesley Long Community HospitalGreensboro, North Carolina  27401
Annie Penn Cancer CenterReidsville, North Carolina  27320
Altru Cancer Center at Altru HospitalGrand Forks, North Dakota  58201
Cancer Treatment CenterWooster, Ohio  44691
Allegheny Cancer Center at Allegheny General HospitalPittsburgh, Pennsylvania  15212
Western Pennsylvania Cancer Institute at Western Pennsylvania HospitalPittsburgh, Pennsylvania  15224-1791
Kaiser Permanente - DenverDenver, Colorado  80205
Kaiser Permanente - LafayetteLafayette, Colorado  80026
Eastern Connecticut Hematology and Oncology AssociatesNorwich, Connecticut  06360
Tunnell Cancer Center at Beebe Medical CenterLewes, Delaware  19958
Herbert D. Kerman Regional Oncology Center - Daytona BeachDaytona Beach, Florida  32114
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross HospitalFort Lauderdale, Florida  33308
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/CandlerSavannah, Georgia  31405
Kaiser Permanente - Moanalua Medical Center and ClinicHonolulu, Hawaii  96819
Elkhart Clinic, LLCElkhart, Indiana  46514-2098
Michiana Hematology-Oncology, PC - South BendMishawaka, Indiana  46545-1470
Reid Hospital & Health Care ServicesRichmond, Indiana  47374
McFarland Clinic, PCAmes, Iowa  50010
Cancer Center of Kansas, PA - ChanuteChanute, Kansas  66720
Cancer Center of Kansas, PA - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Cancer Center of Kansas, PA - KingmanKingman, Kansas  67068
Lawrence Memorial HospitalLawrence, Kansas  66044
Cancer Center of Kansas, PA - NewtonNewton, Kansas  67114
Menorah Medical CenterOverland Park, Kansas  66209
Saint Luke's Hospital - SouthOverland Park, Kansas  66213
Cancer Center of Kansas, PA - ParsonsParsons, Kansas  67357
Cancer Center of Kansas, PA - PrattPratt, Kansas  67124
Cancer Center of Kansas, PA - SalinaSalina, Kansas  67401
Shawnee Mission Medical CenterShawnee Mission, Kansas  66204
Cancer Center of Kansas, PA - WellingtonWellington, Kansas  67152
Cancer Center of Kansas, PA - WichitaWichita, Kansas  67214
Associates in Womens Health, PA - North ReviewWichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas, PA - WinfieldWinfield, Kansas  67156
Ochsner Health Center - BluebonnetBaton Rouge, Louisiana  70809
Greater Baltimore Medical Center Cancer CenterBaltimore, Maryland  21204
Foote Memorial HospitalJackson, Michigan  49201
Haematology-Oncology Associates of Ohio and Michigan, PCLambertville, Michigan  48144
St. Mary Mercy HospitalLivonia, Michigan  48154
Mercy Memorial Hospital - MonroeMonroe, Michigan  48162
St. Joseph Mercy OaklandPontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy HospitalPort Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - SaginawSaginaw, Michigan  48601
Lakeside Cancer Specialists, PLLCSaint Joseph, Michigan  49085
Truman Medical Center - Hospital HillKansas City, Missouri  64108
St. Joseph Medical CenterKansas City, Missouri  64114
Heartland Hematology Oncology Associates, IncorporatedKansas City, Missouri  64118
North Kansas City HospitalKansas City, Missouri  64116
Saint Luke's Cancer Institute at Saint Luke's HospitalKansas City, Missouri  64111
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
Billings Clinic - DowntownBillings, Montana  59107-7000
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
St. James Healthcare Cancer CareButte, Montana  59701
Great Falls Clinic - Main FacilityGreat Falls, Montana  59405
Sletten Cancer Institute at Benefis HealthcareGreat Falls, Montana  59405
Kalispell Medical Oncology at KRMCKalispell, Montana  59901
Alegant Health Cancer Center at Bergan Mercy Medical CenterOmaha, Nebraska  68124
Summa Center for Cancer Care at Akron City HospitalAkron, Ohio  44309-2090
Barberton Citizens HospitalBarberton, Ohio  44203
North Coast Cancer Care - ClydeClyde, Ohio  43410
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer CenterColumbus, Ohio  43210-1240
Hematology Oncology CenterElyria, Ohio  44035
Community Cancer CenterElyria, Ohio  44035
Wayne HospitalGreenville, Ohio  45331
Fisher-Titus Medical CenterNorwalk, Ohio  44857
Flower Hospital Cancer CenterSylvania, Ohio  43560
St. Anne Mercy HospitalToledo, Ohio  43623
Clinton Memorial HospitalWilmington, Ohio  45177
Cleo Craig Cancer Research ClinicLawton, Oklahoma  73505
St. Luke's Cancer Network at St. Luke's HospitalBethlehem, Pennsylvania  18015
McGlinn Family Regional Cancer Center at Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
York Cancer Center at Apple Hill Medical CenterYork, Pennsylvania  17405
Sandra L. Maxwell Cancer CenterCedar City, Utah  84720
Jon and Karen Huntsman Cancer Center at Intermountain Medical CenterMurray, Utah  84157
Val and Ann Browning Cancer Center at McKay-Dee Hospital CenterOgden, Utah  84403
Fredericksburg Oncology, IncorporatedFredericksburg, Virginia  22401
Providence Centralia HospitalCentralia, Washington  98531-9027
Franciscan Cancer Center at St. Joseph Medical CenterTacoma, Washington  98405-3004
Community Comprehensive Cancer Center at Camden-Clark Memorial HospitalParkersburg, West Virginia  26102
Marshfield Clinic - Chippewa CenterChippewa Falls, Wisconsin  54729
Marshfield Clinic Cancer Care at Regional Cancer CenterEau Claire, Wisconsin  54701
Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical CenterGreen Bay, Wisconsin  54311
Saint Joseph's HospitalMarshfield, Wisconsin  54449
Marshfield Clinic - Lakeland CenterMinocqua, Wisconsin  54548
Ministry Medical Group at Saint Mary's HospitalRhinelander, Wisconsin  54501
Marshfield Clinic at Saint Michael's HospitalStevens Point, Wisconsin  54481
Marshfield Clinic - Wausau CenterWausau, Wisconsin  54401
Marshfield Clinic - Weston CenterWeston, Wisconsin  54476
Marshfield Clinic - Wisconsin Rapids CenterWisconsin Rapids, Wisconsin  54494
Cancer Resource Center at King's Daughters Medical CenterAshland, Kentucky  41101
Regional Cancer Center at Memorial Medical CenterSpringfield, Illinois  62781-0001
Saint Louis University Cancer CenterSaint Louis, Missouri  63110
Auburn Regional Center for Cancer CareAuburn, Washington  98002
John H. Stroger, Jr. Hospital of Cook CountyChicago, Illinois  60612-9985
Community HospitalMunster, Indiana  46321
Aurora Sinai Medical CenterMilwaukee, Wisconsin  53201-0342
St. Joseph Hospital Regional Cancer Center - OrangeOrange, California  92868-3849
Phoebe Cancer Center at Phoebe Putney Memorial HospitalAlbany, Georgia  31702
Queen's Cancer Institute at Queen's Medical CenterHonolulu, Hawaii  96813
MetroWest Medical Center - Framingham Union HospitalFramingham, Massachusetts  01702
Good Samaritan Cancer Center at Good Samaritan HospitalKearney, Nebraska  68848-1990
Tucker Center for Cancer Care at Orange Regional Medical CenterMiddletown, New York  10940-4199
Rutherford HospitalRutherfordton, North Carolina  28139
Gibbs Regional Cancer Center at Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
St. Francis HospitalEvanston, Illinois  60202
Frederick Memorial Hospital Regional Cancer Therapy CenterFrederick, Maryland  21701
Lapeer Regional HospitalLapeer, Michigan  48446
St. John's Regional Medical CenterJoplin, Missouri  64804
MBCCOP - Meharry Medical College - NashvilleNashville, Tennessee  37208-3599
Great Falls, Montana  59405
Guardian Oncology and Center for WellnessMissoula, Montana  59804
Roper St. Francis Cancer Center at Roper HospitalCharleston, South Carolina  29401
Louisville Oncology at Norton Cancer Institute - LouisvilleLouisville, Kentucky  40202
Scripps Cancer Center - San DiegoSan Diego, California  92121
Doctors Medical Center - San Pablo CampusSan Pablo, California  94806
Galesburg Clinic, PCGalesburg, Illinois  61401
St. Vincent Healthcare Cancer Care ServicesBillings, Montana  59101
University of Tennessee Cancer Institute - MemphisMemphis, Tennessee  38104
Desert Regional Medical Center Comprehensive Cancer CenterPalm Springs, California  92262
Parvin Radiation OncologyKansas City, Missouri  64116
Midwest Hematology Oncology Group, IncorporatedSaint Louis, Missouri  63109
East Bay Radiation Oncology CenterCastro Valley, California  94546
Contra Costa Regional Medical CenterMartinez, California  94553-3156
El Camino Hospital Cancer CenterMountain View, California  94040
Larry G Strieff MD Medical CorporationOakland, California  94609
Tom K Lee, IncorporatedOakland, California  94609
Bay Area Breast Surgeons, IncorporatedOakland, California  94609
Valley Medical Oncology Consultants - PleasantonPleasanton, California  94588
Kapiolani Medical Center at Pali MomiAiea, Hawaii  96701
Kapiolani Medical Center for Women and ChildrenHonolulu, Hawaii  96826
Straub Clinic and Hospital, IncorporatedHonolulu, Hawaii  96813
Hawaii Medical Center - EastHonolulu, Hawaii  96817
OnCare Hawaii, Incorporated - KuakiniHonolulu, Hawaii  96817
OnCare Hawaii, Incorporated - LusitanaHonolulu, Hawaii  96813
Maui Memorial Medical CenterWailuku, Hawaii  96793
Pacific Cancer Institute - MauiWailuku, Hawaii  96793
Illinois CancerCare - BloomingtonBloomington%, Illinois  61701
Illinois CancerCare - CantonCanton, Illinois  61520
Illinois CancerCare - CarthageCarthage, Illinois  62321
Alexian Brothers Radiation OncologyElk Grove Village, Illinois  60007
Illinois CancerCare - EurekaEureka, Illinois  61530
Illinois CancerCare - GalesburgGalesburg, Illinois  61401
Illinois CancerCare - HavanaHavana, Illinois  62644
Illinois CancerCare - Kewanee ClinicKewanee, Illinois  61443
Illinois CancerCare - MacombMacomb, Illinois  61455
OSF Holy Family Medical CenterMonmouth, Illinois  61462
Illinois CancerCare - MonmouthMonmouth, Illinois  61462
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
York Hospital's Oncology Treatment CenterYork, Maine  03909
Hattiesburg Clinic, PA at Forrest GeneralHattiesburg, Mississippi  39401
Cancer Center of Paoli Memorial HospitalPaoli, Pennsylvania  19301-1792
CCOP - Main Line HealthWynnewood, Pennsylvania  19096
AnMed Cancer CenterAnderson, South Carolina  29621
Cancer Care Center, IncorporatedSalem, Ohio  44460
Center for Cancer Care at Goshen General HospitalGoshen, Indiana  46526
Valley Medical Oncology Consultants - Castro ValleyCastro Valley, California  94546
Valley Medical OncologyFremont, California  94538
Cancer Care AssociatesFresno, California  93720
Memorial Hospital Cancer Center - Colorado SpringsColorado Springs, Colorado  80909
Mount Sinai Hospital Medical CenterChicago, Illinois  60608
Alamance Cancer Center at Alamance Regional Medical CenterBurlington, North Carolina  27216
Marion L. Shepard Cancer Center at Beaufort County HospitalWashington, North Carolina  27889
Nashville Oncology Associates, PCNashville, Tennessee  37203
Associates in Oncology and Hematology - Medical Center DriveRockville, Maryland  20878
St. Agnes Hospital Cancer CenterBaltimore, Maryland  21229
Aurora Women's Pavilion of West Allis Memorial HospitalWest Allis, Wisconsin  53227
Vince Lombardi Cancer Clinic - OshkoshOshkosh, Wisconsin  54904
Kootenai Cancer Center - Coeur d'AleneCoeur d'Alene, Idaho  83814
Illinois CancerCare - CottageGalesburg, Illinois  61401
Saint Francis Hospital Cancer CenterPoughkeepsie, New York  12601
Cherry Tree Cancer CenterHanover, Pennsylvania  17331