Carboplatin and Paclitaxel With or Without Sorafenib Tosylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

Phase 3

Completed

• Conditions: Recurrent Melanoma; Stage IIIC Skin Melanoma; Mucosal Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IV Skin Melanoma
• Interventions: Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Pharmacological Study; Drug: Sorafenib Tosylate; Other: Placebo

• Registration Number: NCT00110019
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This randomized phase III trial studies carboplatin, paclitaxel, and sorafenib tosylate to see how well they work compared to carboplatin and paclitaxel in treating patients with stage III or stage IV melanoma that cannot be removed by surgery. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether giving carboplatin and paclitaxel together with sorafenib tosylate is more effective than carboplatin and paclitaxel in treating melanoma.

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the overall survival of patients with unresectable stage III or stage IV melanoma treated with carboplatin, paclitaxel and placebo versus carboplatin, paclitaxel and sorafenib (sorafenib tosylate).

II. To compare progression-free survival, response rate, and safety of patients with unresectable stage III or stage IV melanoma treated with carboplatin, paclitaxel and placebo versus carboplatin, paclitaxel and sorafenib.

III. To analyze the pharmacokinetic and pharmacogenetic properties of sorafenib including angiogenesis, monooxygenases polymorphisms and multidrug resistance (MDR).

IV. To assess the association of expression markers in the patient tumor with clinical outcome.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive sorafenib tosylate orally (PO) twice daily (BID) (approximately every 12 hours) on days 2-19.

Arm II: Patients receive paclitaxel and carboplatin as in Arm I. Patients also receive placebo PO BID (approximately every 12 hours) on days 2-19.

In both arms, treatment repeats every 21 days for 10 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or who achieve a partial response or complete response may continue to receive sorafenib tosylate or placebo alone BID (approximately every 12 hours) on days 1-21. Courses with sorafenib tosylate or placebo repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2005-05-03
• Study First Submitted QC: 2005-05-03
• Study First Posted: 2005-05-04
• Study Start: 2005-06
• Primary Completion: 2011-01
• Study Completion: 2012-08
• Results First Submitted: 2012-08-28
• Results First Submitted QC: 2012-08-28
• Results First Posted: 2012-09-27
• Status Verified: 2015-07
• Last Update Submitted: 2015-09-28
• Last Update Posted: 2015-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 823

Inclusion Criteria

• Histological or cytological confirmed melanoma that is metastatic or unresectable; patients must have a history of cutaneous, mucosal or unknown primary site

• Patients who have received prior systemic cytotoxic chemotherapy for treatment of melanoma are ineligible; the following groups are eligible with regard to prior systemic therapy either in the adjuvant or metastatic disease setting:

  • No prior therapy

  • Immunotherapy consisting of interferon, interleukin-2, granulocyte macrophage colony-stimulating factor (GM-CSF) or vaccine

  • One prior investigational therapy (cannot be chemotherapy or an inhibitor of rat sarcoma [Ras], serine/threonine kinase [Raf], or mitogen-activated protein kinase kinase [MEK])

    • NOTE: Chemotherapy given via isolated limb perfusion is allowed

• Prior radiation therapy is allowed; however, if radiation has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions

• All sites of disease must be evaluated within 4 weeks of registration; patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• White blood count >= 3,000/mm^3

• Absolute granulocyte count >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• Serum creatinine =< 2.0 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) >= 40 ml/min (neither drug is cleared by the kidney)

• Total bilirubin =< 1.5 x ULN (< 3.0 x ULN in the presence of Gilbert's disease)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN (=< 5.0 ULN in the presence of liver metastases)

• International normalized ratio (INR) =< 1.5 and a partial thromboplastin time (PTT) within normal limits (patients who are on therapeutic anticoagulation with warfarin should have documentation of a normal prothrombin time [PT]/PTT prior to initiating that therapy)

• Patients must not have ocular melanoma

• Patients must have discontinued immunotherapy or radiation therapy at least 4 weeks prior to initiation of treatment and recovered from adverse events due to those agents

• Patients must not receive any other investigational agents during the period on study or the four weeks prior to initiation of treatment

• Patients must not have a history or clinical evidence of brain metastasis; patients must be evaluated with a head magnetic resonance imaging (MRI) within 4 weeks prior to enrollment

• Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for >= 5 years prior to the time of randomization

• Patients must not have any evidence of bleeding diathesis

• Patients must not have a serious intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, clinically significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction, unstable angina), New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease within 1 year prior to study entry, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), rifampin or St. John's Wort

• Women must not be pregnant or breast-feeding

• All females of childbearing potential must have a blood test or urine study within 4 weeks prior to registration to rule out pregnancy

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately as well

• Human immunodeficiency virus (HIV)-positive patients are excluded from the study

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (paclitaxel, carboplatin, sorafenib tosylate)	Laboratory Biomarker Analysis	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive sorafenib tosylate PO BID (approximately every 12 hours) on days 2-19.
Arm I (paclitaxel, carboplatin, sorafenib tosylate)	Pharmacological Study	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive sorafenib tosylate PO BID (approximately every 12 hours) on days 2-19.
Arm I (paclitaxel, carboplatin, sorafenib tosylate)	Sorafenib Tosylate	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive sorafenib tosylate PO BID (approximately every 12 hours) on days 2-19.
Arm II (carboplatin, paclitaxel, placebo)	Carboplatin	Patients receive paclitaxel and carboplatin as in Arm I. Patients also receive placebo PO BID (approximately every 12 hours) on days 2-19.
Arm II (carboplatin, paclitaxel, placebo)	Laboratory Biomarker Analysis	Patients receive paclitaxel and carboplatin as in Arm I. Patients also receive placebo PO BID (approximately every 12 hours) on days 2-19.
Arm II (carboplatin, paclitaxel, placebo)	Pharmacological Study	Patients receive paclitaxel and carboplatin as in Arm I. Patients also receive placebo PO BID (approximately every 12 hours) on days 2-19.
Arm II (carboplatin, paclitaxel, placebo)	Paclitaxel	Patients receive paclitaxel and carboplatin as in Arm I. Patients also receive placebo PO BID (approximately every 12 hours) on days 2-19.
Arm II (carboplatin, paclitaxel, placebo)	Placebo	Patients receive paclitaxel and carboplatin as in Arm I. Patients also receive placebo PO BID (approximately every 12 hours) on days 2-19.
Arm I (paclitaxel, carboplatin, sorafenib tosylate)	Carboplatin	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive sorafenib tosylate PO BID (approximately every 12 hours) on days 2-19.
Arm I (paclitaxel, carboplatin, sorafenib tosylate)	Paclitaxel	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive sorafenib tosylate PO BID (approximately every 12 hours) on days 2-19.

Primary Outcome Measures

Name	Time	Method
Overall Survival	Survival was assessed every 3 months if patient is < 2 years from study entry. Every 6 months is patient is 2-5 years from study entry.	Overall survival is defined as time from study entry to death from any cause. The comparison of overall survival was conducted in intention-to-treat population.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival	Tumor response was assessed after every 2 cycles during cycle 1 through 10, and every 3 cycles after cycle 10. Survival was assessed every 3 months if patient is < 2 years from study entry, and every 6 months if 2-5 years from study entry.	Progression-free survival was defined as time from study entry to disease progression or death from any cause, whichever occurred first. Patients without disease progression were censored at last date of assessment. Disease progression was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0.
Objective Response (Complete and Partial Response) Rate	Tumor response was assessed after every 2 cycles during cycle 1 through 10. After cycle 10, tumor response was assessed after every 3 cycles.	Tumor response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Objective response =complete response (CR) + partial response (PR). Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum of longest diameters.

Trial Locations

Locations (219)

Sinai Hospital of Baltimore; 🇺🇸 Baltimore, Maryland, United States

Bay Area Tumor Institute; 🇺🇸 Oakland, California, United States

Kaiser Permanente-Redwood City; 🇺🇸 Redwood City, California, United States

Kaiser Permanente-Santa Teresa-San Jose; 🇺🇸 San Jose, California, United States

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Boulder Community Hospital; 🇺🇸 Boulder, Colorado, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center; 🇺🇸 Burbank, California, United States

Kaiser Permanente-Roseville; 🇺🇸 Roseville, California, United States

Kaiser Permanente Medical Center - Santa Clara; 🇺🇸 Santa Clara, California, United States

Kaiser Permanente-Vallejo; 🇺🇸 Vallejo, California, United States

USC / Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Swedish Medical Center; 🇺🇸 Englewood, Colorado, United States

Memorial Medical Center; 🇺🇸 Springfield, Illinois, United States

Northeast Georgia Medical Center; 🇺🇸 Gainesville, Georgia, United States

Longmont United Hospital; 🇺🇸 Longmont, Colorado, United States

MedStar Franklin Square Medical Center/Weinberg Cancer Institute; 🇺🇸 Baltimore, Maryland, United States

Memorial Hospital of South Bend; 🇺🇸 South Bend, Indiana, United States

Carle Clinic-Urbana Main; 🇺🇸 Urbana, Illinois, United States

North Suburban Medical Center; 🇺🇸 Thornton, Colorado, United States

Cancer Center of Kansas-Wichita Medical Arts Tower; 🇺🇸 Wichita, Kansas, United States

Sky Ridge Medical Center; 🇺🇸 Lone Tree, Colorado, United States

NorthShore University HealthSystem-Evanston Hospital; 🇺🇸 Evanston, Illinois, United States

Southern Regional Medical Center; 🇺🇸 Riverdale, Georgia, United States

Hinsdale Hematology Oncology Associates Incorporated; 🇺🇸 Hinsdale, Illinois, United States

Piedmont Hospital; 🇺🇸 Atlanta, Georgia, United States

Trinity Medical Center; 🇺🇸 Moline, Illinois, United States

Medical Center of Central Georgia; 🇺🇸 Macon, Georgia, United States

Decatur Memorial Hospital; 🇺🇸 Decatur, Illinois, United States

Beebe Medical Center; 🇺🇸 Lewes, Delaware, United States

Jupiter Medical Center; 🇺🇸 Jupiter, Florida, United States

Fort Wayne Medical Oncology and Hematology Inc-Parkview; 🇺🇸 Fort Wayne, Indiana, United States

Southwest Florida Regional Medical Center; 🇺🇸 Fort Meyers, Florida, United States

Dekalb Medical Center; 🇺🇸 Decatur, Georgia, United States

Holy Cross Hospital; 🇺🇸 Fort Lauderdale, Florida, United States

Cedar Valley Medical Specialists; 🇺🇸 Waterloo, Iowa, United States

Mount Sinai Medical Center; 🇺🇸 Miami Beach, Florida, United States

Carle Cancer Center; 🇺🇸 Urbana, Illinois, United States

Cedar Rapids Oncology Association; 🇺🇸 Cedar Rapids, Iowa, United States

Advocate Sherman Hospital; 🇺🇸 Elgin, Illinois, United States

Kansas City CCOP; 🇺🇸 Prairie Village, Kansas, United States

Central Maine Medical Center; 🇺🇸 Lewiston, Maine, United States

Greater Baltimore Medical Center; 🇺🇸 Baltimore, Maryland, United States

Summa Akron City Hospital/Cooper Cancer Center; 🇺🇸 Akron, Ohio, United States

University of Iowa/Holden Comprehensive Cancer Center; 🇺🇸 Iowa City, Iowa, United States

Laura and Issac Perlmutter Cancer Center at NYU Langone; 🇺🇸 New York, New York, United States

Mercy Medical Center; 🇺🇸 Canton, Ohio, United States

Columbus CCOP; 🇺🇸 Columbus, Ohio, United States

Oakwood Hospital and Medical Center; 🇺🇸 Dearborn, Michigan, United States

Oncology Care Associates PLLC; 🇺🇸 Saint Joseph, Michigan, United States

Cancer Center of Kansas - Chanute; 🇺🇸 Chanute, Kansas, United States

Mercy Hospital Saint Louis; 🇺🇸 Saint Louis, Missouri, United States

West Michigan Cancer Center; 🇺🇸 Kalamazoo, Michigan, United States

Salina Regional Health Center; 🇺🇸 Salina, Kansas, United States

Hackensack University Medical CCOP; 🇺🇸 Hackensack, New Jersey, United States

Cancer Center of Kansas - Wellington; 🇺🇸 Wellington, Kansas, United States

North Memorial Medical Health Center; 🇺🇸 Robbinsdale, Minnesota, United States

Saint Louis-Cape Girardeau CCOP; 🇺🇸 Saint Louis, Missouri, United States

Minnesota Oncology and Hematology PA-Woodbury; 🇺🇸 Woodbury, Minnesota, United States

Stony Brook University Medical Center; 🇺🇸 Stony Brook, New York, United States

Interlakes Foundation Inc-Rochester; 🇺🇸 Rochester, New York, United States

Frontier Cancer Center and Blood Institute-Billings; 🇺🇸 Billings, Montana, United States

Cleveland Clinic Wooster Specialty Center; 🇺🇸 Wooster, Ohio, United States

East Carolina University; 🇺🇸 Greenville, North Carolina, United States

Commonwealth Hematology Oncology PC-Worcester; 🇺🇸 Worcester, Massachusetts, United States

Grand Rapids Clinical Oncology Program; 🇺🇸 Grand Rapids, Michigan, United States

Freeman Health System; 🇺🇸 Joplin, Missouri, United States

Unity Hospital; 🇺🇸 Fridley, Minnesota, United States

Veterans Adminstration New Jersey Health Care System; 🇺🇸 East Orange, New Jersey, United States

Singing River Hospital; 🇺🇸 Pascagoula, Mississippi, United States

CoxHealth South Hospital; 🇺🇸 Springfield, Missouri, United States

Center for Cancer Care and Research; 🇺🇸 Saint Louis, Missouri, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

William Beaumont Hospital-Royal Oak; 🇺🇸 Royal Oak, Michigan, United States

Carolinas Medical Center/Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

Hematology Oncology Associates of Central New York-East Syracuse; 🇺🇸 East Syracuse, New York, United States

Mount Carmel Health Center West; 🇺🇸 Columbus, Ohio, United States

Sanford Medical Center-Fargo; 🇺🇸 Fargo, North Dakota, United States

Glens Falls Hospital; 🇺🇸 Glens Falls, New York, United States

Saint John Macomb-Oakland Hospital; 🇺🇸 Warren, Michigan, United States

Regions Hospital; 🇺🇸 Saint Paul, Minnesota, United States

State University of New York Upstate Medical University; 🇺🇸 Syracuse, New York, United States

Mid Dakota Clinic; 🇺🇸 Bismarck, North Dakota, United States

Springfield Regional Medical Center; 🇺🇸 Springfield, Ohio, United States

Licking Memorial Hospital; 🇺🇸 Newark, Ohio, United States

Cleveland Clinic Cancer Center Independence; 🇺🇸 Independence, Ohio, United States

MidHudson Regional Hospital of Westchester Medical Center; 🇺🇸 Poughkeepsie, New York, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Adena Regional Medical Center; 🇺🇸 Chillicothe, Ohio, United States

Delaware County Memorial Hospital; 🇺🇸 Drexel Hill, Pennsylvania, United States

Saint Mary Medical and Regional Cancer Center; 🇺🇸 Langhorne, Pennsylvania, United States

University of Virginia Cancer Center; 🇺🇸 Charlottesville, Virginia, United States

University of Chicago Comprehensive Cancer Center; 🇺🇸 Chicago, Illinois, United States

Case Western Reserve University; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Group Health Cooperative-Seattle; 🇺🇸 Seattle, Washington, United States

Massachusetts General Hospital Cancer Center; 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center; 🇺🇸 Miami, Florida, United States

Indiana University/Melvin and Bren Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Nevada Cancer Research Foundation CCOP; 🇺🇸 Las Vegas, Nevada, United States

Kaiser Permanente-San Diego Mission; 🇺🇸 San Diego, California, United States

Veterans Administration-San Diego Medical Center; 🇺🇸 San Diego, California, United States

Abbott-Northwestern Hospital; 🇺🇸 Minneapolis, Minnesota, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

California Pacific Medical Center-Pacific Campus; 🇺🇸 San Francisco, California, United States

Vanderbilt University/Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Wayne State University/Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Saint John Hospital and Medical Center; 🇺🇸 Detroit, Michigan, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Cancer Care Associates; 🇺🇸 Oklahoma City, Oklahoma, United States

University of Alabama at Birmingham Cancer Center; 🇺🇸 Birmingham, Alabama, United States

Presbyterian - Saint Lukes Medical Center - Health One; 🇺🇸 Denver, Colorado, United States

Western Oncology Research Consortium; 🇺🇸 Portland, Oregon, United States

Kaiser Permanente; 🇺🇸 Portland, Oregon, United States

Froedtert and the Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Kaiser Permanente-San Francisco; 🇺🇸 San Francisco, California, United States

Kaiser Permanente-Santa Rosa; 🇺🇸 Santa Rosa, California, United States

University of Vermont College of Medicine; 🇺🇸 Burlington, Vermont, United States

University of Hawaii Cancer Center; 🇺🇸 Honolulu, Hawaii, United States

Kaiser Permanente - Sacramento; 🇺🇸 Sacramento, California, United States

The Medical Center of Aurora; 🇺🇸 Aurora, Colorado, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Saint Joseph Mercy Hospital; 🇺🇸 Ann Arbor, Michigan, United States

University of Michigan Comprehensive Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Marin Cancer Care Inc; 🇺🇸 Greenbrae, California, United States

Mercy Hospital Fort Smith; 🇺🇸 Ft. Smith, Arkansas, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

Kaiser Permanente-Richmond; 🇺🇸 Richmond, California, United States

Stanford Cancer Institute; 🇺🇸 Palo Alto, California, United States

Saint Joseph Hospital - Orange; 🇺🇸 Orange, California, United States

Santa Rosa Memorial Hospital; 🇺🇸 Sana Rosa, California, United States

Porter Adventist Hospital; 🇺🇸 Denver, Colorado, United States

Exempla Saint Joseph Hospital; 🇺🇸 Denver, Colorado, United States

Penrose-Saint Francis Healthcare; 🇺🇸 Colorado Springs, Colorado, United States

Memorial Regional Hospital/Joe DiMaggio Children's Hospital; 🇺🇸 Hollywood, Florida, United States

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

Baptist Cancer Institute; 🇺🇸 Jacksonville, Florida, United States

Christiana Care Health System-Christiana Hospital; 🇺🇸 Newark, Delaware, United States

Broward Health Medical Center; 🇺🇸 Fort Lauderdale, Florida, United States

Lakeland Regional Cancer Center; 🇺🇸 Lakeland, Florida, United States

Phoebe Putney Memorial Hospital; 🇺🇸 Albany, Georgia, United States

Atlanta Regional CCOP; 🇺🇸 Atlanta, Georgia, United States

South Georgia Medical Center; 🇺🇸 Valdosta, Georgia, United States

Swedish Covenant Hospital; 🇺🇸 Chicago, Illinois, United States

IU Health Bloomington; 🇺🇸 Bloomington, Indiana, United States

Saint Joseph Regional Medical Center-Mishawaka; 🇺🇸 Mishawaka, Indiana, United States

Franciscan Saint Anthony Health-Michigan City; 🇺🇸 Michigan City, Indiana, United States

Physicians' Clinic of Iowa PC; 🇺🇸 Cedar Rapids, Iowa, United States

Heartland Oncology and Hematology LLP; 🇺🇸 Council Bluffs, Iowa, United States

Genesis Medical Center - East Campus; 🇺🇸 Davenport, Iowa, United States

University of Kansas Cancer Center; 🇺🇸 Kansas City, Kansas, United States

Johns Hopkins University/Sidney Kimmel Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Frederick Memorial Hospital; 🇺🇸 Frederick, Maryland, United States

Cancer Center of Kansas - Main Office; 🇺🇸 Wichita, Kansas, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Munson Medical Center; 🇺🇸 Traverse City, Michigan, United States

Hurley Medical Center; 🇺🇸 Flint, Michigan, United States

Saint Francis Regional Medical Center; 🇺🇸 Shakopee, Minnesota, United States

Park Nicollet Clinic - Saint Louis Park; 🇺🇸 Saint Louis Park, Minnesota, United States

United Hospital; 🇺🇸 Saint Paul, Minnesota, United States

Mercy Hospital Springfield; 🇺🇸 Springfield, Missouri, United States

Dartmouth Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

Altru Cancer Center; 🇺🇸 Grand Forks, North Dakota, United States

Doctors Hospital; 🇺🇸 Columbus, Ohio, United States

Aultman Health Foundation; 🇺🇸 Canton, Ohio, United States

Grant Medical Center; 🇺🇸 Columbus, Ohio, United States

Saint Rita's Medical Center; 🇺🇸 Lima, Ohio, United States

Grady Memorial Hospital; 🇺🇸 Delaware, Ohio, United States

Oncology Hematology Associates of Northern Pennsylvania; 🇺🇸 Dubois, Pennsylvania, United States

Geisinger Medical Center; 🇺🇸 Danville, Pennsylvania, United States

Penn State Milton S Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

PinnacleHealth Cancer Center-Community Campus; 🇺🇸 Harrisburg, Pennsylvania, United States

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pennsylvania/Abramson Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Pennsylvania Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pittsburgh Cancer Institute (UPCI); 🇺🇸 Pittsburgh, Pennsylvania, United States

Scranton Hematology Oncology; 🇺🇸 Scranton, Pennsylvania, United States

Pottstown Memorial Medical Center; 🇺🇸 Pottstown, Pennsylvania, United States

Hematology and Oncology Associates of North East Pennsylvania; 🇺🇸 Scranton, Pennsylvania, United States

Chester County Hospital; 🇺🇸 West Chester, Pennsylvania, United States

Geisinger Medical Group; 🇺🇸 State College, Pennsylvania, United States

Jennersville Regional Hospital; 🇺🇸 West Grove, Pennsylvania, United States

Kent County Hospital; 🇺🇸 Warwick, Rhode Island, United States

WellSpan Health-York Hospital; 🇺🇸 York, Pennsylvania, United States

Lankenau Medical Center; 🇺🇸 Wynnewood, Pennsylvania, United States

McLeod Regional Medical Center; 🇺🇸 Florence, South Carolina, United States

Rapid City Regional Hospital; 🇺🇸 Rapid City, South Dakota, United States

Sanford Cancer Center-Oncology Clinic; 🇺🇸 Sioux Falls, South Dakota, United States

East Tennessee Baptist Hospital-Mercy Health Partners; 🇺🇸 Knoxville, Tennessee, United States

Erlanger Medical Center; 🇺🇸 Chattanooga, Tennessee, United States

Martha Jefferson Hospital; 🇺🇸 Charlottesville, Virginia, United States

Danville Regional Medical Center; 🇺🇸 Danville, Virginia, United States

Virginia Oncology Associates-Hampton; 🇺🇸 Hampton, Virginia, United States

West Virginia University Charleston; 🇺🇸 Charleston, West Virginia, United States

Swedish Medical Center-First Hill; 🇺🇸 Seattle, Washington, United States

Saint Mary's Medical Center; 🇺🇸 Huntington, West Virginia, United States

Edwards Comprehensive Cancer Center; 🇺🇸 Huntington, West Virginia, United States

West Virginia University Healthcare; 🇺🇸 Morgantown, West Virginia, United States

Fox Valley Hematology and Oncology; 🇺🇸 Appleton, Wisconsin, United States

Gundersen Lutheran Medical Center; 🇺🇸 La Crosse, Wisconsin, United States

Aurora Cancer Care-Southern Lakes; 🇺🇸 Elkhorn, Wisconsin, United States

Holy Family Memorial Hospital; 🇺🇸 Manitowoc, Wisconsin, United States

Sydney West Area Health Service-Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Marshfield Clinic; 🇺🇸 Marshfield, Wisconsin, United States

Montana Cancer Consortium NCORP; 🇺🇸 Billings, Montana, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Florida Hospital Orlando; 🇺🇸 Orlando, Florida, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

Montefiore Medical Center-Wakefield Campus; 🇺🇸 Bronx, New York, United States

Medical Oncology and Hematology Associates-Des Moines; 🇺🇸 Des Moines, Iowa, United States

Medical Oncology and Hematology Associates-Laurel; 🇺🇸 Des Moines, Iowa, United States

Dean Hematology and Oncology Clinic; 🇺🇸 Madison, Wisconsin, United States

University of Wisconsin Hospital and Clinics; 🇺🇸 Madison, Wisconsin, United States

Wayne Memorial Hospital; 🇺🇸 Goldsboro, North Carolina, United States