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RTOG-1010 A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of Her2-Overexpressing Esophageal Adenocarcinoma

Description

PRIMARY OBJECTIVES: l. To determine if trastuzumab increases disease-free survival when combined with trimodality treatment (radiation plus chemotherapy followed by surgery) for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing esophageal adenocarcinoma. SECONDARY OBJECTIVES: I. To evaluate if the addition of trastuzumab to trimodality treatment increases the pathologic complete response rate and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma. II. To develop a tissue bank of tumor tissue from patients with non-metastatic esophageal adenocarcinoma. III. To determine molecular correlates of complete pathologic response, disease-free survival, and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma treated with neoadjuvant and maintenance trastuzumab. IV. To evaluate predictors of cardiotoxicity in patients with esophageal cancer treated with trastuzumab and chemoradiation. V. To evaluate adverse events associated with the addition of trastuzumab to trimodality treatment for patients with non-metastatic esophageal adenocarcinoma. TERTIARY OBJECTIVES: I. To determine if the addition of trastuzumab to trimodality treatment improves the patient-reported Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E) Esophageal Cancer Subscale (ECS) score. II. To determine if an improvement in the FACT-E ECS score at 6-8 weeks post completion of neoadjuvant chemoradiation correlates with pathologic complete response. III. To determine if pathologic complete response correlates with the FACT-E ECS score at 1 year and/or 2 years from the start of chemoradiation. IV. To determine if the addition of trastuzumab to trimodality treatment improves the Swallow Index and Eating Index Subscale scores of the FACT-E. V. To determine if the addition of trastuzumab to paclitaxel, carboplatin, and radiation impacts quality-adjusted survival. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive trastuzumab intravenously (IV) over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57 and paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Beginning 21-56 days after surgery, patients receive trastuzumab IV over 30-90 minutes. Treatment repeats every 21 days for 13 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Within 5-8 weeks after completion of radiotherapy, all patients undergo surgery. After completion of study therapy, patients are followed up every 4 months for 2 years and then yearly thereafter.

Phase

Phase 3 - a treatment has shown activity against a particular disease, where it is either added to existing treatment or compared to the standard treatment.

Inclusion and Exclusion Criteria

  • Pathologically confirmed primary adenocarcinoma of the esophagus that involves the mid (up to 25 cm), distal, or esophagogastric junction; the cancer may involve the stomach up to 5 cm
  • Endoscopy with biopsy
  • PRIOR TO STEP 1 REGISTRATION BUT WITHIN 56 DAYS PRIOR TO STEP 2 REGISTRATION
  • Intent to submit tissue for central HER2 testing
  • Stage T1N1-2, T2-3N0-2, according to the American Joint Committee on Cancer (AJCC) 7th edition staging, based on the following minimum diagnostic work-up:
  • Chest/abdominal/pelvic computed tomography (CT) or whole-body positron emission tomography (PET)/CT (NOTE: if CT is performed at this time point, whole-body PET/CT will be required prior to step 2 registration; PET/CT of skull base to mid-thigh is acceptable) (NOTE: if adenopathy is noted on CT or whole-body PET/CT scan, an endoscopic ultrasound is not required prior to STEP 2 registration as long as adequate tissue has been obtained for central HER2 testing)
  • Patients may have regional adenopathy including para-esophageal, gastric, gastrohepatic and celiac nodes; if celiac adenopathy is present, it must be =< 2 cm
  • Patients with tumors at the level of the carina or above must undergo bronchoscopy to exclude fistula
  • Zubrod performance status 0-2
  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
  • Platelets >=100,000 cells/mm^3
  • Hemoglobin >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is acceptable)
  • Creatinine =< 2 times upper limit of normal
  • Bilirubin =< 1.5 times upper limit of normal
  • Aspartate aminotransferase (AST) =< 3.0 times upper limit of normal
  • For women of childbearing potential, a negative serum or urine pregnancy test
  • Patients must sign a study-specific informed consent prior to study entry
  • CONDITIONS FOR PATIENT ELIGIBILITY PRIOR TO STEP 2 REGISTRATION (HER2-POSITIVE PATIENTS ONLY)
  • HER2 expressing adenocarcinoma of the esophagus centrally
  • Surgical consultation to confirm that patient will be able to undergo curative resection after completion of chemoradiation within 56 days prior to step 2 registration
  • Radiation oncology consultation to confirm that disease can be encompassed in a radiotherapy field within 56 days prior to step 2 registration
  • Consultation with a medical oncologist within 56 days prior to step 2 registration
  • Stage T1N1-2, T2-3N0-2, according to the AJCC 7th edition staging, based upon the following minimum diagnostic work-up:
  • History/physical examination, with documentation of the patient's weight, within 14 days prior to step 2 registration
  • Whole-body PET/CT scan within 56 days prior to step 2 registration (if only CT performed prior to step 1 registration)
  • Endoscopic ultrasound within 56 days prior to step 2 registration, unless the patient is found to have adenopathy per CT or whole-body PET/CT scan
  • Electrocardiogram (EKG) within 56 days prior to step 2 registration
  • Serum creatinine =< 2 x the upper limit or normal within 14 days prior to step 2 registration
  • Zubrod performance status 0-2 within 14 days prior to step 2 registration
  • For women of childbearing potential, a negative serum pregnancy test within 14 days prior to step 2 registration
  • Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal by cardiac echocardiogram (echo) or multi gated acquisition (MUGA) scan within 56 days prior to step 2 registration
  • Women of childbearing potential and sexually active male participants must agree to practice adequate contraception while on study and for at least 60 days following the last dose of chemotherapy or trastuzumab

  • Patients with cervical esophageal carcinoma
  • Patients with T1N0 disease, T4 disease, and proximal esophageal cancers (15-24 cm)
  • Prior systemic chemotherapy for esophageal cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiation therapy for esophageal cancer or prior chest radiotherapy
  • Prior anthracycline or taxane
  • Evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi
  • Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 2 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are permissible)
  • Medical contraindications to esophagectomy
  • Prior therapy with any agent targeting the HER2 pathway or human epidermal growth factor receptor 1 (HER1) (epidermal growth factor receptor [EGFR]) pathway
  • Prior therapy with trastuzumab
  • Prior allergic reaction to the study drugs involved in this protocol or to a monoclonal antibody
  • Previous history of congestive heart failure
  • Severe, active comorbidity, defined as follows:
  • Unstable angina in the last 6 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immunocompromised patients
  • Pregnant or nursing women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

Sites

  • California

    • University of Southern California/Norris Cancer Center, Los Angeles, California, 90033
    • USC / Norris Comprehensive Cancer Center, Los Angeles, California, 90033
    • Los Angeles County-USC Medical Center, Los Angeles, California, 90033
    • Cedars-Sinai Medical Center, Los Angeles, California, 90048
    • Providence Saint Joseph Medical Center/Disney Family Cancer Center, Burbank, California, 91505
    • Memorial Medical Center, Modesto, California, 95355
    • Kaiser Permanente-Santa Teresa-San Jose, San Jose, California, 95119
    • Kaiser Permanente Radiation Oncology Cancer Treatment Center, Santa Clara, California, 95051
    • Kaiser Permanente Medical Center - Santa Clara, Santa Clara, California, 95051
    • El Camino Hospital, Mountain View, California, 94040
    • Kaiser Permanente, Fremont, Fremont, California, 94538
    • Stanford University Hospitals and Clinics, Stanford, California, 94305
    • Palo Alto Medical Foundation Health Care, Palo Alto, California, 94301
    • Kaiser Permanente-Stockton, Stockton, California, 95210
    • Kaiser Permanente-Redwood City, Redwood City, California, 94063
    • Epic Care-Dublin, Dublin, California, 94568
    • Kaiser Permanente-Deer Valley Medical Center, Antioch, California, 94531
    • East Bay Radiation Oncology Center, Castro Valley, California, 94546
    • Kaiser Permanente San Leandro, San Leandro, California, 94577
    • Mills - Peninsula Hospitals, Burlingame, California, 94010
    • Highland General Hospital, Oakland, California, 94602
    • Kaiser Permanente-Walnut Creek, Walnut Creek, California, 94596
    • Kaiser Permanente Cancer Treatment Center, South San Francisco, California, 94080
    • Kaiser Permanente-South San Francisco, South San Francisco, California, 94080
    • Kaiser Permanente-Oakland, Oakland, California, 94611
    • Kaiser Permanente Oakland-Broadway, Oakland, California, 94611
    • Epic Care-Oakland, Oakland, California, 94612
    • Bay Area Tumor Institute, Oakland, California, 94609
    • Alta Bates Summit Medical Center - Summit Campus, Oakland, California, 94609
    • Larry G Strieff MD Medical Corporation, Oakland, California, 94609
    • Bay Area Breast Surgeons Inc, Oakland, California, 94609
    • Alta Bates Summit Medical Center-Herrick Campus, Berkeley, California, 94704
    • Kaiser Permanente-San Francisco, San Francisco, California, 94115
    • California Pacific Medical Center-Pacific Campus, San Francisco, California, 94118
    • Sutter Cancer Centers Radiation Oncology Services-Cameron Park, Cameron Park, California, 95682
    • Kaiser Permanente-South Sacramento, Sacramento, California, 95823
    • South Sacramento Cancer Center, Sacramento, California, 95823
    • Kaiser Permanente-Richmond, Richmond, California, 94801
    • Doctors Medical Center- JC Robinson Regional Cancer Center, San Pablo, California, 94806
    • Kaiser Permanente-Rancho Cordova Cancer Center, Rancho Cardova, California, 95670
    • University of California at Davis Cancer Center, Sacramento, California, 95817
    • University of California Davis Comprehensive Cancer Center, Sacramento, California, 95817
    • Mercy San Juan Medical Center, Carmichael, California, 95608
    • Kaiser Permanente - Sacramento, Sacramento, California, 95825
    • Sutter General Hospital, Sacramento, California, 95816
    • Sutter Solano Medical Center/Cancer Center, Vallejo, California, 94589
    • Kaiser Permanente-Vallejo, Vallejo, California, 94589
    • Sutter Cancer Centers Radiation Oncology Services-Vacaville, Vacaville, California, 95687
    • Kaiser Permanente-Roseville, Roseville, California, 95661
    • Sutter Cancer Centers Radiation Oncology Services-Roseville, Roseville, California, 95661
    • Kaiser Permanente-San Rafael, San Rafael, California, 94903
    • Kaiser Permanente Medical Center-Vacaville, Vacaville, California, 95688
    • The Permanente Medical Group-Roseville Radiation Oncology, Roseville, California, 95678
    • Sutter Cancer Research Consortium, Novato, California, 94945
    • Sutter Cancer Centers Radiation Oncology Services-Auburn, Auburn, California, 95603
    • Rohnert Park Cancer Center, Rohnert Park, California, 94928
    • Kaiser Permanente-Santa Rosa, Santa Rosa, California, 95403
    • Enloe Medical Center, Chico, California, 95926
  • Nevada

    • 21st Century Oncology - Fort Apache, Las Vegas, Nevada, 89148
    • Cancer and Blood Specialists-Fort Apache, Las Vegas, Nevada, 89148
    • HealthCare Partners Medical Group Oncology/Hematology-San Martin, Las Vegas, Nevada, 89113
    • Summerlin Hospital Medical Center, Las Vegas, Nevada, 89144
    • Las Vegas Cancer Center-Henderson, Henderson, Nevada, 89052
    • Cancer and Blood Specialists-Henderson, Henderson, Nevada, 89052
    • Cancer and Blood Specialists-Tenaya, Las Vegas, Nevada, 89128
    • HealthCare Partners Medical Group Oncology/Hematology-Tenaya, Las Vegas, Nevada, 89128
    • Radiation Oncology Centers of Nevada Southeast, Las Vegas, Nevada, 89119
    • 21st Century Oncology - Henderson, Henderson, Nevada, 89074
    • Comprehensive Cancer Centers of Nevada-Southeast Henderson, Henderson, Nevada, 89074
    • University Medical Center of Southern Nevada, Las Vegas, Nevada, 89102
    • 21st Century Oncology - Vegas Sunrise, Las Vegas, Nevada, 89109
    • HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway, Las Vegas, Nevada, 89109
    • HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills, Las Vegas, Nevada, 89149
    • Nevada Cancer Research Foundation CCOP, Las Vegas, Nevada, 89106
    • Cancer and Blood Specialists-Shadow, Las Vegas, Nevada, 89106
    • Cancer Therapy and Integrative Medicine, Las Vegas, Nevada, 89121
  • Utah

    • Dixie Medical Center Regional Cancer Center, Saint George, Utah, 84770
    • Sandra L Maxwell Cancer Center, Cedar City, Utah, 84720
    • Utah Valley Regional Medical Center, Provo, Utah, 84604
    • American Fork Hospital / Huntsman Intermountain Cancer Center, American Fork, Utah, 84003
    • Huntsman Intermountain Cancer Center-American Fork Hospital, American Fork, Utah, 84003
    • Intermountain Medical Center, Murray, Utah, 84157
    • Utah Cancer Specialists-Salt Lake City, Salt Lake City, Utah, 84106
    • LDS Hospital, Salt Lake City, Utah, 84143
    • McKay-Dee Hospital Center, Ogden, Utah, 84403
    • Logan Regional Hospital, Logan, Utah, 84321
  • Arizona

    • Mayo Clinic Hospital, Phoenix, Arizona, 85054
    • Mayo Clinic in Arizona, Scottsdale, Arizona, 85259
    • University of Arizona Health Sciences Center, Tucson, Arizona, 85724
  • Colorado

    • Mercy Medical Center, Durango, Colorado, 81301
    • Saint Mary Corwin Medical Center, Pueblo, Colorado, 81004
    • Rocky Mountain Cancer Centers - Pueblo, Pueblo, Colorado, 81008
    • Colorado Blood Cancer Institute, Denver, Colorado, 80907
    • Rocky Mountain Cancer Centers-Penrose, Colorado Springs, Colorado, 80907
    • Mountain Blue Cancer Care Center, Golden, Colorado, 80401
    • Saint Anthony Hospital, Lakewood, Colorado, 80228
    • Rocky Mountain Cancer Centers-Lakewood, Lakewood, Colorado, 80228
    • Rocky Mountain Cancer Centers-Littleton, Littleton, Colorado, 80120
    • Littleton Adventist Hospital, Littleton, Colorado, 80122
    • Sky Ridge Medical Center, Lone Tree, Colorado, 80124
    • Rocky Mountain Cancer Centers-Sky Ridge, Lone Tree, Colorado, 80124
    • Exempla Saint Joseph Hospital, Denver, Colorado, 80218
    • Presbyterian - Saint Lukes Medical Center - Health One, Denver, Colorado, 80218
    • Rocky Mountain Cancer Centers-Midtown, Denver, Colorado, 80218
    • Breast Cancer Care Consultants, Greenwood Village, Colorado, 80111
    • Rocky Mountain Cancer Centers-Thornton, Thornton, Colorado, 80260
    • Rose Medical Center, Denver, Colorado, 80220
    • Rocky Mountain Cancer Centers-Rose, Denver, Colorado, 80220
    • North Suburban Medical Center, Thornton, Colorado, 80229
    • Rocky Mountain Cancer Centers-Aurora, Aurora, Colorado, 80012
    • The Medical Center of Aurora, Aurora, Colorado, 80012
    • Rocky Mountain Cancer Centers-Longmont, Longmont, Colorado, 80501
    • Rocky Mountain Cancer Centers-Parker, Parker, Colorado, 80138
    • Parker Adventist Hospital, Parker, Colorado, 80138
    • Poudre Valley Radiation Oncology, Fort Collins, Colorado, 80528
    • Poudre Valley Hospital, Fort Collins, Colorado, 80524
  • New Mexico

    • University of New Mexico, Albuquerque, New Mexico, 87106
    • University of New Mexico Cancer Center, Albuquerque, New Mexico, 87106
  • Oregon

    • Salem Hospital, Salem, Oregon, 97301
    • Salem Hospital, Salem, Oregon, 97301
    • Providence Willamette Falls Medical Center, Oregon City, Oregon, 97045
    • Providence Newberg Medical Center, Newberg, Oregon, 97132
  • Idaho

    • Saint Joseph Regional Medical Center, Lewiston, Idaho, 83501
    • Kootenai Medical Center, Coeur D'Alene, Idaho, 83814
    • Kootenai Cancer Center, Post Falls, Idaho, 83854
  • Washington

    • Saint John Medical Center, Longview, Washington, 98632
    • Providence Regional Cancer System-Centralia, Centralia, Washington, 98531
    • Multicare Health System, Tacoma, Washington, 98415
    • Good Samaritan Community Hospital, Puyallup, Washington, 98372
    • MultiCare Good Samaritan Hospital, Puyallup, Washington, 98372
    • Saint Clare Hospital, Lakewood, Washington, 98499
    • MultiCare Allenmore Hospital, Tacoma, Washington, 98405
    • Northwest Medical Specialties PLLC, Tacoma, Washington, 98405
    • Auburn Regional Medical Center, Auburn, Washington, 98001
    • Saint Francis Hospital, Federal Way, Washington, 98003
    • Highline Medical Center-Main Campus, Burien, Washington, 98166
    • Olympic Medical Cancer Care Center, Sequim, Washington, 98384
    • Overlake Hospital Medical Center, Bellevue, Washington, 98004
    • Seattle Cancer Care Alliance, Seattle, Washington, 98109
    • Providence Regional Cancer Partnership, Everett, Washington, 98201
    • PeaceHealth Saint Joseph Medical Center, Bellingham, Washington, 98225
  • Montana

    • Saint James Community Hospital and Cancer Treatment Center, Butte, Montana, 59701
    • Saint Patrick Hospital - Community Hospital, Missoula, Montana, 59802
    • Saint Peter's Community Hospital, Helena, Montana, 59601
    • Montana Cancer Consortium CCOP, Billings, Montana, 59101
    • Saint Vincent Healthcare, Billings, Montana, 59101
    • Benefis Healthcare- Sletten Cancer Institute, Great Falls, Montana, 59405
    • Kalispell Regional Medical Center, Kalispell, Montana, 59901
  • Texas

    • Covenant Medical Center-Lakeside, Lubbock, Texas, 79410
    • University of Texas Southwestern Medical Center, Dallas, Texas, 75390
    • Methodist Hospital, Houston, Texas, 77030
    • UTMB Cancer Center at Victory Lakes, League City, Texas, 77573
    • UTMB Cancer Center at Victory Lakes, League City, Texas, 77573
  • Wyoming

    • Welch Cancer Center, Sheridan, Wyoming, 82801
  • Nebraska

    • Good Samaritan Hospital, Kearney, Nebraska, 68847
  • Kansas

    • Salina Regional Health Center, Salina, Kansas, 67401
    • Saint Luke's South Hospital, Overland Park, Kansas, 66213
    • Kansas City Cancer Centers-Southwest, Overland Park, Kansas, 66210
    • Menorah Medical Center, Overland Park, Kansas, 66209
  • Oklahoma

    • Tulsa Cancer Institute, Tulsa, Oklahoma, 74146
  • North Dakota

    • Trinity Cancer Care Center, Minot, North Dakota, 58701
    • Essentia Health Cancer Center-South University Clinic, Fargo, North Dakota, 58103
  • Missouri

    • Mercy Hospital-Joplin, Joplin, Missouri, 64804
    • Freeman Health System, Joplin, Missouri, 64804
    • Heartland Regional Medical Center, Saint Joseph, Missouri, 64506
    • Kansas City Cancer Center - South, Kansas City, Missouri, 64131
    • Research Medical Center, Kansas City, Missouri, 64132
    • Heartland Hematology and Oncology Associates Incorporated, Kansas City, Missouri, 64118
    • Liberty Radiation Oncology Center, Liberty, Missouri, 64068
    • Centerpoint Medical Center LLC, Independence, Missouri, 64057
    • Saint Luke's East - Lee's Summit, Lee's Summit, Missouri, 64086
    • Central Care Cancer Center-Carrie J Babb Cancer Center, Bolivar, Missouri, 65613
    • CoxHealth Cancer Center, Branson, Missouri, 65616
    • Capital Region Medical Center-Goldschmidt Cancer Center, Jefferson City, Missouri, 65109
    • Saint John's Clinic-Rolla-Cancer and Hematology, Rolla, Missouri, 65401
    • Missouri Baptist Sullivan Hospital, Sullivan, Missouri, 63080
    • Siteman Cancer Center - Saint Peters, Saint Peters, Missouri, 63376
    • Parkland Health Center-Bonne Terre, Bonne Terre, Missouri, 63628
    • Saint Luke's Hospital, Chesterfield, Missouri, 63017
    • Barnes-Jewish West County Hospital, Saint Louis, Missouri, 63141
    • Missouri Baptist Outpatient Center-Sunset Hills, Sunset Hills, Missouri, 63127
    • Saint Anthony's Medical Center, Saint Louis, Missouri, 63128
    • Saint Louis Cancer and Breast Institute-South City, Saint Louis, Missouri, 63109
    • Washington University School of Medicine, Saint Louis, Missouri, 63110
    • Sainte Genevieve County Memorial Hospital, Sainte Genevieve, Missouri, 63670
    • Southeast Cancer Center, Cape Girardeau, Missouri, 63703
    • Saint Francis Medical Center, Cape Girardeau, Missouri, 63703
  • Iowa

    • McFarland Clinic PC-Jefferson, Jefferson, Iowa, 50129
    • Mercy Medical Center-West Lakes, West Des Moines, Iowa, 50266
    • Mercy Cancer Center-West Lakes, Clive, Iowa, 50325
    • McFarland Clinic PC-Boone, Boone, Iowa, 50036
    • Mercy Medical Center - Des Moines, Des Moines, Iowa, 50314
    • Mary Greeley Medical Center, Ames, Iowa, 50010
    • McFarland Clinic PC-Marshalltown, Marshalltown, Iowa, 50158
    • Oncology Associates at Mercy Medical Center, Cedar Rapids, Iowa, 52403
    • Cedar Rapids Oncology Association, Cedar Rapids, Iowa, 52403
    • Constantinou, Costas L MD (UIA Investigator), Bettendorf, Iowa, 52722
  • Minnesota

    • Rice Memorial Hospital, Willmar, Minnesota, 56201
    • Ridgeview Medical Center, Waconia, Minnesota, 55387
    • Fairview-Southdale Hospital, Edina, Minnesota, 55435
    • Fairview Ridges Hospital, Burnsville, Minnesota, 55337
    • Metro-Minnesota CCOP, Saint Louis Park, Minnesota, 55416
    • Park Nicollet Clinic - Saint Louis Park, Saint Louis Park, Minnesota, 55416
    • North Memorial Medical Health Center, Robbinsdale, Minnesota, 55422
    • Abbott-Northwestern Hospital, Minneapolis, Minnesota, 55407
    • Hennepin County Medical Center, Minneapolis, Minnesota, 55415
    • Mercy Hospital, Coon Rapids, Minnesota, 55433
    • Unity Hospital, Fridley, Minnesota, 55432
    • United Hospital, Saint Paul, Minnesota, 55102
    • Regions Hospital, Saint Paul, Minnesota, 55101
    • Saint John's Hospital - Healtheast, Maplewood, Minnesota, 55109
    • Mayo Clinic, Rochester, Minnesota, 55905
    • Essentia Health Saint Mary's Medical Center, Duluth, Minnesota, 55805
    • Essentia Health Cancer Center, Duluth, Minnesota, 55805
  • Illinois

    • Spector, David MD (UIA Investigator), Moline, Illinois, 61265
    • Trinity Medical Center, Moline, Illinois, 61265
    • Garneau, Stewart C MD (UIA Investigator), Moline, Illinois, 61265
    • Memorial Hospital of Carbondale, Carbondale, Illinois, 62902
    • Centralia Oncology Clinic, Centralia, Illinois, 62801
    • Good Samaritan Regional Health Center, Mount Vernon, Illinois, 62864
    • Cancer Care Center of Decatur, Decatur, Illinois, 62526
    • SwedishAmerican Regional Cancer Center/ACT, Rockford, Illinois, 61107
    • Presence Saint Mary's Hospital, Kankakee, Illinois, 60901
    • Northwest Community Hospital, Arlington Heights, Illinois, 60005
    • Loyola University Medical Center, Maywood, Illinois, 60153
    • West Suburban Medical Center, River Forest, Illinois, 60305
    • Mac Neal Hospital, Berwyn, Illinois, 60402
    • University of Illinois, Chicago, Illinois, 60612
    • Northwestern University, Chicago, Illinois, 60611
  • Wisconsin

    • Gundersen Lutheran Medical Center, La Crosse, Wisconsin, 54601
    • Sacred Heart Hospital, Eau Claire, Wisconsin, 54701
    • Marshfield Clinic Cancer Center at Sacred Heart, Eau Claire, Wisconsin, 54701
    • Marshfield Clinic-Rice Lake Center, Rice Lake, Wisconsin, 54868
    • Marshfield Clinic, Marshfield, Wisconsin, 54449
    • Saint Joseph's Hospital, Marshfield, Wisconsin, 54449
    • Marshfield Clinic Cancer Care at Saint Michael's Hospital, Stevens Point, Wisconsin, 54481
    • Saint Michael's Hospital, Stevens Point, Wisconsin, 54481
    • Diagnostic and Treatment Center, Weston, Wisconsin, 54476
    • Marshfield Clinic - Weston Center, Weston, Wisconsin, 54476
    • Marshfield Clinic-Minocqua Center, Minocqua, Wisconsin, 54548
    • Aurora Cancer Care-Southern Lakes, Elkhorn, Wisconsin, 53121
    • Marshfield Clinic at James Beck Cancer Center, Rhinelander, Wisconsin, 54501
    • Aurora Cancer Care-Burlington, Burlington, Wisconsin, 53105
    • Vince Lombardi Cancer Clinic - Oshkosh, Oshkosh, Wisconsin, 54904
    • Aurora Cancer Care-Waukesha, Waukesha, Wisconsin, 53188
    • Aurora Advanced Healthcare Inc-Menomonee Falls, Menomonee Falls, Wisconsin, 53051
    • The Alyce and Elmore Kraemer Cancer Care Center, West Bend, Wisconsin, 53095
    • Aurora West Allis Medical Center, West Allis, Wisconsin, 53227
    • Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin, 53226
    • Aurora Cancer Care-Milwaukee West, Wauwatosa, Wisconsin, 53226
    • Aurora Cancer Care-Kenosha South, Kenosha, Wisconsin, 53142
    • Aurora Sinai Medical Center, Milwaukee, Wisconsin, 53233
    • Aurora Cancer Care-Milwaukee, Milwaukee, Wisconsin, 53209
    • Aurora Cancer Care-Grafton, Grafton, Wisconsin, 53024
    • Saint Mary's Hospital, Green Bay, Wisconsin, 54303
    • Green Bay Oncology Limited at Saint Mary's Hospital, Green Bay, Wisconsin, 54303
    • Green Bay Oncology - Oconto Falls, Oconto Falls, Wisconsin, 54154
    • Saint Vincent Hospital, Green Bay, Wisconsin, 54301
    • Clement J. Zablocki VA Medical Center, Milwaukee, Wisconsin, 53295
    • Vince Lombardi Cancer Clinic-Sheboygan, Sheboygan, Wisconsin, 53081
    • Vince Lombardi Cancer Clinic, Two Rivers, Wisconsin, 54241
    • Vince Lombardi Cancer Clinic-Marinette, Marinette, Wisconsin, 54143
    • Bay Area Medical Center, Marinette, Wisconsin, 54143
    • Green Bay Oncology - Sturgeon Bay, Sturgeon Bay, Wisconsin, 54235
  • Mississippi

    • University of Mississippi Medical Center, Jackson, Mississippi, 39216
  • Louisiana

    • Ochsner Medical Center Jefferson, New Orleans, Louisiana, 70121
  • Alabama

    • Providence Hospital, Mobile, Alabama, 36608
    • University of Alabama at Birmingham, Birmingham, Alabama, 35294
    • University of Alabama at Birmingham, Birmingham, Alabama, 35233
    • The Kirklin Clinic at Acton Road, Birmingham, Alabama, 35243
  • Tennessee

    • Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, 37232
  • Indiana

    • Michiana Hematology Oncology-PC Westville, Westville, Indiana, 46391
    • Michiana Hematology Oncology PC-Plymouth, Plymouth, Indiana, 46563
    • Northern Indiana Cancer Research Consortium, South Bend, Indiana, 46628
    • Franciscan Saint Francis Health-Indianapolis, Indianapolis, Indiana, 46237
    • Michiana Hematology Oncology PC-South Bend, South Bend, Indiana, 46601
    • Memorial Hospital of South Bend, South Bend, Indiana, 46601
    • Saint Joseph Regional Medical Center-Mishawaka, Mishawaka, Indiana, 46545
    • Michiana Hematology Oncology PC-Mishawaka, Mishawaka, Indiana, 46545
    • Michiana Hematology Oncology PC-Elkhart, Elkhart, Indiana, 46514
    • IU Health Ball Memorial Hospital, Muncie, Indiana, 47303
    • IU Health Ball Memorial Hospital, Muncie, Indiana, 47303
  • Michigan

    • Green Bay Oncology - Iron Mountain, Iron Mountain, Michigan, 49801
    • Marie Yeager Cancer Center, Saint Joseph, Michigan, 49085
    • Lakeland Hospital, St. Joseph, Michigan, 49085
    • Lakeland Community Hospital, Niles, Michigan, 49120
    • Green Bay Oncology - Escanaba, Escanaba, Michigan, 49431
    • Bronson Methodist Hospital, Kalamazoo, Michigan, 49007
    • West Michigan Cancer Center, Kalamazoo, Michigan, 49007
    • Borgess Medical Center, Kalamazoo, Michigan, 49001
    • Sparrow Hospital, Lansing, Michigan, 48912
  • Ohio

    • University of Cincinnati, Cincinnati, Ohio, 45267
    • University Pointe, West Chester, Ohio, 45069
  • Kentucky

    • Baptist Health Lexington, Lexington, Kentucky, 40503
  • Georgia

    • Piedmont Fayette Hospital, Fayetteville, Georgia, 30214
    • Grady Health System, Atlanta, Georgia, 30303
    • Emory University/Winship Cancer Institute, Atlanta, Georgia, 30322
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