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Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has Been Removed by Surgery

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT01274338
Collaborator
(none)
1,673
Enrollment
950
Locations
6
Arms
289.1
Anticipated Duration (Months)
1.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized phase III trial studies ipilimumab to see how well it works compared to high-dose interferon alfa-2b in treating patients with high-risk stage III-IV melanoma that has been removed by surgery. Monoclonal antibodies, such as ipilimumab, may interfere with the ability of tumor cells to grow and spread. Interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of melanoma and other cancers. It is not yet known whether ipilimumab is more effective than interferon alfa-2b in treating patients with melanoma.

Condition or Disease Intervention/Treatment Phase
  • Biological: Ipilimumab
  • Biological: Alfa Interferon
 Phase 3

Detailed Description

PRIMARY OBJECTIVES:

  1. To evaluate recurrence-free survival (RFS) between patients randomized to receive post-operative adjuvant ipilimumab given at either 10 mg/kg (high dose ipilimumab; HIP) or 3 mg/kg (low dose ipilimumab: LIP) versus those randomized to receive high-dose interferon alfa-2b (HDI) utilizing a hierarchical design assessing HIP versus HDI first and LIP versus HDI second (if the first comparison is significant).

  2. To evaluate overall survival (OS) between patients randomized to receive post-operative adjuvant ipilimumab given at either 10 mg/kg (HIP) or 3 mg/kg (LIP) versus those randomized to receive HDI utilizing a hierarchical design assessing HIP versus HDI first and LIP versus HDI second (if the first comparison is significant).

SECONDARY OBJECTIVES:

  1. To evaluate safety and tolerability of post-operative adjuvant ipilimumab therapy given at either 10 mg/kg (HIP) or 3 mg/kg (LIP).

  2. Among patients enrolled by Clinical Community Oncology programs (CCOPs), to compare the global quality of life (QOL) between the ipilimumab arms versus HDI using Functional Assessment of Cancer Therapy (FACT)-General (G) form and to evaluate the effect of treatment-related side effects that may have an impact on the health-related domains of QOL using Functional Assessment of Chronic Illness Therapy (FACIT)-diarrhea (D) and FACT-biological response modifiers (BRM).

OUTLINE: Patients age >= 18 are randomized to Arms A, B, or C. Additional cohort of up to 45 patients aged 12-17 are randomized to Arms D, E, or F after adult accrual has completed on arms A, B and C. Arms D, E and F will follow the same treatment regimen as Arms A, B and C, respectively.

ARM A (HIP): Patients receive induction high-dose ipilimumab intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (closed accrual as of 4/4/14) (adult accrual has completed to Arms A, B, and C as of 8/15/2014)

ARM B (HDI): Patients receive induction high-dose recombinant interferon alfa-2b IV over 20 minutes on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alfa-2b subcutaneously (SC) on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. (adult accrual has completed to Arms A, B, and C as of 8/15/2014)

ARM C (LIP): Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (adult accrual has completed to Arms A, B, and C as of 8/15/2014)

ARM D (HIP; Pediatric): Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.

ARM E (HDI; Pediatric): Patients receive induction high-dose recombinant interferon alfa-2b IV over 20 minutes on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alfa-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity

ARM F (LIP; Pediatric): Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for up to 20 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
1673 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Randomized Study of Adjuvant Ipilimumab Anti-CTLA4 Therapy Versus High-Dose Interferon a-2b for Resected High Risk Melanoma
Actual Study Start Date :
May 25, 2011
Actual Primary Completion Date :
Feb 15, 2019
Anticipated Study Completion Date :
Jun 26, 2035

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A (HIP)

Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (closed accrual as of 4/4/14) (adult accrual has completed to Arms A, B, and C as of 8/15/2014)

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • MDX-010
  • MDX-CTLA4

    		•
    Experimental: Arm B (HDI)

    Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. (adult accrual has completed to Arms A, B, and C as of 8/15/2014)

    Biological: Alfa Interferon
    Given IV and SC
    Other Names:
  • Interferon Alfa - 2b
  • Intron A
  • IFN-alpha 2b
  • NSC #377523

    		•
    Experimental: Arm C (LIP)

    Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (adult accrual has completed to Arms A, B, and C as of 8/15/2014)

    Biological: Ipilimumab
    Given IV
    Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • MDX-010
  • MDX-CTLA4

    		•
    Experimental: Arm D (HIP; Pediatric)

    Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (ages 12-17)

    Biological: Ipilimumab
    Given IV
    Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • MDX-010
  • MDX-CTLA4

    		•
    Experimental: Arm E (HDI; Pediatric)

    Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. (ages 12-17)

    Biological: Alfa Interferon
    Given IV and SC
    Other Names:
  • Interferon Alfa - 2b
  • Intron A
  • IFN-alpha 2b
  • NSC #377523

    		•
    Experimental: Arm F (LIP; Pediatric)

    Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (ages 12-17)

    Biological: Ipilimumab
    Given IV
    Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • MDX-010
  • MDX-CTLA4

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Recurrence-free Survival (RFS; Arm B [HDI] vs. Arm C [LIP]) [Assessed every 3 months for 2 years, then every 6 months for years 3-5 and then annually up to 8 years]

      Recurrence-free survival is defined as the time from randomization to recurrence or death, whichever occurs first. The following criteria constitute the only acceptable evidence of disease recurrence. Lung and liver: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease. Central Nervous System: A positive brain CT or MRI scan or CSF cytology. Cutaneous, Subcutaneous and Lymph Node Recurrence: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease. Bone and Other Organs: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease identified on two different radiologic studies: i.e., positive nuclear bone scan or PET scan and contrast GI series or ultrasound, X-ray or CT of abdomen for abdominal disease.

    2. 5-year Overall Survival (OS) Rate (Arm B [HDI] vs. Arm C [LIP]) [Assessed every 3 months for 2 years, then every 6 months for years 3-5]

      Overall survival is defined as the time from randomization to death or date last known alive.

    3. Recurrence-free Survival (RFS; Arm A [HIP] vs. Arm B [HDI]) [Assessed every 3 months for 2 years, then every 6 months for years 3-5 and then annually up to 8 years]

      Recurrence-free survival is defined as the time from randomization to recurrence or death, whichever occurs first. The following criteria constitute the only acceptable evidence of disease recurrence. Lung and liver: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease. Central Nervous System: A positive brain CT or MRI scan or CSF cytology. Cutaneous, Subcutaneous and Lymph Node Recurrence: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease. Bone and Other Organs: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease identified on two different radiologic studies: i.e., positive nuclear bone scan or PET scan and contrast GI series or ultrasound, X-ray or CT of abdomen for abdominal disease.

    4. 5-year Overall Survival (OS) Rate (Arm A [HIP] vs. Arm B [HDI]) [Assessed every 3 months for 2 years, then every 6 months for years 3-5]

      Overall survival is defined as the time from randomization to death or date last known alive.

    Secondary Outcome Measures

    1. Change in FACT-G (Functional Assessment of Cancer Therapy - General) Total Score From Baseline to 3 Months [Assessed at baseline and 3 months]

      The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-G total score ranges between 0 and 108. The higher the score, the better the quality of life. Change in FACT-G total score from baseline to 3 months was calculated as month 3 score - baseline score.

    2. Change in FACIT-D (Functional Assessment of Cancer Therapy - Diarrhea) Diarrhea Subscale Score From Baseline to 3 Months [Assessed at baseline and 3 months]

      The diarrhea subscale of The Functional Assessment of Chronic Illness Therapy - Diarrhea (FACIT-D) is an 11-item questionnaire with a scale of 0-4. The FACIT-D diarrhea subscale score ranges between 0 and 44. The higher the score, the better the quality of life. Change in FACIT-D diarrhea subscale score from baseline to 3 months was calculated as month 3 score - baseline score.

    3. Change in FACT-BRM (Functional Assessment of Cancer Therapy - Biologic Response Modifiers) Total Score From Baseline to 3 Months [Assessed at baseline and 3 months]

      The Functional Assessment of Cancer Therapy - Biologic Response Modifiers (FACT-BRM) is a questionnaire including FACT-G (The Functional Assessment of Cancer Therapy - General) and additional sections addressing physical and mental quality of life aspects. It is a 40-item questionnaire with a scale of 0-4. The FACT-BRM total score ranges between 0 and 160. The higher the score, the better the quality of life. Change in FACT-BRM total score from baseline to 3 months is calculated as month 3 score - baseline score.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • All patients must have disease-free status documented by a complete physical examination and imaging studies within 4 weeks prior to randomization; imaging studies must include a total body positron emission tomography (PET)-computed tomography (CT) scan (with or without brain) and brain magnetic resonance imaging (MRI) or CT (if MRI is contraindicated); if PET-CT cannot be done, CT of neck, chest, abdomen, and pelvis should be done

    • If for some reason a CT cannot be done, an MRI may be done instead; any other imaging studies if performed (eg, bone scan) must show no evidence of disease

    • Patients must have primary cutaneous melanoma that belong to one of the following

    American Joint Commission on Cancer (AJCC) stages (2009 AJCC Melanoma Staging System):

    • Stage IIIB

    • T1-4b N1a M0

    • T1-4b N2a M0

    • T1-4b N1b M0

    • T1-4b N2b M0

    • T1-4b N2c M0

    • Stage IIIC

    • T1-4b N1b M0

    • T1-4b N2b M0

    • T1-4b N2c M0

    • Any T N3 M0

    • Stage IV

    • M1a

    • M1b

    • NOTE: patients with stage IV melanoma must have normal lactate dehydrogenase (LDH) and either distant skin, subcutaneous, lymph node, or lung metastases, but no other visceral metastases in order to be eligible; for patients with resected stage IV melanoma, LDH within the institutional upper limit of normal (ULN) must be documented within 4 weeks prior to randomization

    • Patients with disease recurrence after adequate surgical excision of the original primary cutaneous/unknown primary melanoma are allowed even if they don't fit the strict staging criteria, but only as follows:

    • Recurrence in a regional lymph node basin after a prior complete lymph node dissection; relapsed disease must be completely surgically resected with free margins

    • Recurrence in the form of in-transit or satellite metastases or distant skin/subcutaneous, nodal, or lung metastases that are completely surgically resected with free margins

    • Recurrence in a regional lymph node basin; relapsed disease must be completely surgically resected with free margins

    • Patients with unknown primary melanoma (Tx) who present with cutaneous, subcutaneous, nodal and/or lung metastases that are completely surgically resected with free margins are allowed; these patients are allowed even if they don't fit the strict staging criteria; for stage IV patients LDH within the institutional ULN must be documented within 4 weeks prior to randomization (M1c is not eligible)

    • NOTE: all subjects should be classified as IIIB, IIIC, M1a or M1b including subjects with disease recurrence after adequate surgical excision of the original primary melanoma; that is the treating team/physician investigator should review an overall TNM status (that includes primary tumor presentation and disease recurrence status) and provide a designation of IIIB, IIIC, M1a or M1b

    • Patients must be randomized within 84 days (12 weeks) of surgical resection; if more than one surgical procedure is required to render the patient disease-free, the patient must be randomized within 12 weeks of the last surgery

    • NOTE: patients with clinically positive lymph nodes for melanoma involvement or those with positive lymph nodes identified through lymphoscintigraphic and/or dye lymphographic techniques in the groin, axilla, or neck should have additional lymphadenectomy in those sites; the complete lymph node dissection procedure would be considered as the last surgery in counting the 84 days unless a subsequent surgical procedure(s) was clinically required to ensure the disease free status

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

    • Patients should be carefully screened for depression at baseline and if there are indications or a history of depression it is strongly recommended that these patients be closely followed together with behavioral health or psychiatric medical support

    • All females of childbearing potential must have a blood test or urine study during screening to rule out pregnancy

    • Woman of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of ipilimumab or HDI, in such a manner that the risk of pregnancy is minimized; women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential

    • Men of fathering potential and WOCBP must be using an adequate method of contraception to avoid conception/pregnancy throughout the study and for up to 26 weeks after the last dose of ipilimumab or HDI in such a manner that the risk of pregnancy is minimized

    • White blood cell (WBC) >= 3,000/uL (obtained within 4 weeks prior to randomization)

    • Absolute neutrophil count (ANC) >= 1,500/uL (obtained within 4 weeks prior to randomization)

    • Platelets >= 100 x 10^3/uL (obtained within 4 weeks prior to randomization)

    • Hemoglobin >= 10 g/dL (obtained within 4 weeks prior to randomization)

    • Serum creatinine =< 1.5 mg/dL (obtained within 4 weeks prior to randomization)

    • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN (obtained within 4 weeks prior to randomization)

    • Serum bilirubin =< 1.5 x ULN, (except patients with Gilbert's syndrome, who must have a total bilirubin less than 3.0 mg/dL) (obtained within 4 weeks prior to randomization)

    Exclusion Criteria:

    • Prior adjuvant treatment (chemotherapy, biotherapy, or limb perfusion) after the resection(s) that make(s) them eligible for this trial

    • NOTE: previous radiation therapy, including after the surgical resection, is allowed as long as 21 days have elapsed between the radiation and initiation of this adjuvant systemic therapy

    • Prior treatment with anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) monoclonal antibodies or prior CTLA-4 inhibitor or agonist or prior clusters of differentiation (CD)137 agonist or prior interferon-alfa

    • Other forms of prior treatment for melanoma (e.g., aldesleukin [IL-2], anti-tumor vaccine, chemotherapy) are allowed if given before the resection(s) that make(s) the patient eligible for this trial, but these must have been completed at least 4 weeks prior to randomization

    • Active infection requiring current treatment with parenteral antibiotics

    • Other significant medical, surgical, or psychiatric conditions or require any medication or treatment that in the opinion of the investigator may interfere with compliance, make the administration of ipilimumab or HDI hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea; patients with a baseline of frequent diarrhea (e.g. irritable bowel syndrome) are not eligible

    • Patients with an established diagnosis of depression that, in the assessment of the investigator may make the administration of interferon (IFN)-alfa or ipilimumab hazardous, should not be enrolled on this protocol; the risks and benefits of being treated with standard adjuvant IFN-alfa should be weighed very carefully in consultation with behavioral health or psychiatry

    • Documented history of inflammatory bowel disease (including ulcerative colitis and Crohn's disease) or diverticulitis (history of diverticulosis is allowed)

    • Autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed; replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of these classes of medication for at least 2 weeks prior to randomization are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study

    • Exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis [e.g., Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and Myasthenia Gravis); other central nervous system (CNS) autoimmune disease (e.g., poliomyelitis, multiple sclerosis)

    • Patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible

    • Prior infectious disease vaccination (e.g., standard influenza, H1N1 influenza, pneumococcal, meningococcal, or tetanus toxoid) within 4 weeks prior to randomization

    • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

    • Other current malignancies are not eligible; patients with other malignancies are eligible if they have been continuously disease free for > 5 years prior to the time of randomization; patients with prior history at any time of any in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ are eligible; patients with prior history of basal or squamous skin cancer are eligible; patients who have had multiple primary melanomas are eligible

    • Pregnant or breast-feeding

    • NOTE: a woman of childbearing potential (WOCBP) is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); post-menopause is defined as:

    • Amenorrhea >= 12 consecutive months without another cause, or

    • For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level

    = 35 mIU/mL ; men or WOCBP who are unwilling or unable to strictly follow this requirement are not eligible

    • A positive pregnancy test at baseline

    • Active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; patients must have negative testing for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) within 4 weeks prior to randomization

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Cancer Center Birmingham Alabama United States 35233
    2 Providence Hospital Mobile Alabama United States 36608
    3 University of South Alabama Mitchell Cancer Institute Mobile Alabama United States 36688
    4 Alaska Regional Hospital Anchorage Alaska United States 99508
    5 Providence Alaska Medical Center Anchorage Alaska United States 99508
    6 Fairbanks Memorial Hospital Fairbanks Alaska United States 99701
    7 Banner MD Anderson Cancer Center Gilbert Arizona United States 85234
    8 University of Arizona Cancer Center-Orange Grove Campus Tucson Arizona United States 85704
    9 Banner University Medical Center - Tucson Tucson Arizona United States 85719
    10 University of Arizona Cancer Center-North Campus Tucson Arizona United States 85719
    11 Mercy Hospital Fort Smith Fort Smith Arkansas United States 72903
    12 Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro Jonesboro Arkansas United States 72401
    13 John L McClellan Memorial Veterans Hospital Little Rock Arkansas United States 72205
    14 University of Arkansas for Medical Sciences Little Rock Arkansas United States 72205
    15 Highlands Oncology Group-Rogers Rogers Arkansas United States 72758
    16 Kaiser Permanente-Deer Valley Medical Center Antioch California United States 94531
    17 PCR Oncology Arroyo Grande California United States 93420
    18 Sutter Auburn Faith Hospital Auburn California United States 95602
    19 Sutter Cancer Centers Radiation Oncology Services-Auburn Auburn California United States 95603
    20 Sutter Cancer Centers Radiation Oncology Services-Cameron Park Cameron Park California United States 95682
    21 Sutter Davis Hospital Davis California United States 95616
    22 Kaiser Permanente-Fremont Fremont California United States 94538
    23 Kaiser Permanente-Fresno Fresno California United States 93720
    24 Saint Jude Medical Center Fullerton California United States 92835
    25 Marin Cancer Care Inc Greenbrae California United States 94904
    26 UC San Diego Moores Cancer Center La Jolla California United States 92093
    27 The Angeles Clinic and Research Institute - West Los Angeles Office Los Angeles California United States 90025
    28 Mattel Children's Hospital UCLA Los Angeles California United States 90095
    29 UCLA / Jonsson Comprehensive Cancer Center Los Angeles California United States 90095
    30 Memorial Medical Center Modesto California United States 95355
    31 Kaiser Permanente-Modesto Modesto California United States 95356
    32 Community Hospital of Monterey Peninsula Monterey California United States 93940
    33 Palo Alto Medical Foundation-Camino Division Mountain View California United States 94040
    34 Palo Alto Medical Foundation-Gynecologic Oncology Mountain View California United States 94040
    35 Sutter Cancer Research Consortium Novato California United States 94945
    36 Kaiser Permanente-Oakland Oakland California United States 94611
    37 Saint Joseph Hospital - Orange Orange California United States 92868
    38 UC Irvine Health/Chao Family Comprehensive Cancer Center Orange California United States 92868
    39 Palo Alto Medical Foundation Health Care Palo Alto California United States 94301
    40 Stanford Cancer Institute Palo Alto Palo Alto California United States 94304
    41 VA Palo Alto Health Care System Palo Alto California United States 94304
    42 Eisenhower Medical Center Rancho Mirage California United States 92270
    43 Kaiser Permanente-Redwood City Redwood City California United States 94063
    44 Kaiser Permanente-Richmond Richmond California United States 94801
    45 Kaiser Permanente-Roseville Roseville California United States 95661
    46 Sutter Cancer Centers Radiation Oncology Services-Roseville Roseville California United States 95661
    47 Sutter Roseville Medical Center Roseville California United States 95661
    48 Sutter Medical Center Sacramento Sacramento California United States 95816
    49 Kaiser Permanente-South Sacramento Sacramento California United States 95823
    50 Kaiser Permanente - Sacramento Sacramento California United States 95825
    51 Sharp Memorial Hospital San Diego California United States 92123
    52 California Pacific Medical Center-Pacific Campus San Francisco California United States 94115
    53 Kaiser Permanente-San Francisco San Francisco California United States 94115
    54 Kaiser Permanente-Santa Teresa-San Jose San Jose California United States 95119
    55 Kaiser Permanente San Leandro San Leandro California United States 94577
    56 Pacific Central Coast Health Center-San Luis Obispo San Luis Obispo California United States 93401
    57 Kaiser Permanente-San Rafael San Rafael California United States 94903
    58 Kaiser Permanente Medical Center - Santa Clara Santa Clara California United States 95051
    59 Palo Alto Medical Foundation-Santa Cruz Santa Cruz California United States 95065
    60 Kaiser Permanente-Santa Rosa Santa Rosa California United States 95403
    61 Sutter Pacific Medical Foundation Santa Rosa California United States 95403
    62 Kaiser Permanente-South San Francisco South San Francisco California United States 94080
    63 Kaiser Permanente-Stockton Stockton California United States 95210
    64 Palo Alto Medical Foundation-Sunnyvale Sunnyvale California United States 94086
    65 Sutter Cancer Centers Radiation Oncology Services-Vacaville Vacaville California United States 95687
    66 Kaiser Permanente Medical Center-Vacaville Vacaville California United States 95688
    67 Kaiser Permanente-Vallejo Vallejo California United States 94589
    68 Kaiser Permanente-Walnut Creek Walnut Creek California United States 94596
    69 Presbyterian Intercommunity Hospital Whittier California United States 90602
    70 Rocky Mountain Cancer Centers-Aurora Aurora Colorado United States 80012
    71 The Medical Center of Aurora Aurora Colorado United States 80012
    72 University of Colorado Hospital Aurora Colorado United States 80045
    73 Boulder Community Hospital Boulder Colorado United States 80301
    74 Rocky Mountain Cancer Centers-Boulder Boulder Colorado United States 80304
    75 Penrose-Saint Francis Healthcare Colorado Springs Colorado United States 80907
    76 Rocky Mountain Cancer Centers-Penrose Colorado Springs Colorado United States 80907
    77 UCHealth Memorial Hospital Central Colorado Springs Colorado United States 80909
    78 Kaiser Permanente-Franklin Denver Colorado United States 80205
    79 Porter Adventist Hospital Denver Colorado United States 80210
    80 Colorado Blood Cancer Institute Denver Colorado United States 80218
    81 Presbyterian - Saint Lukes Medical Center - Health One Denver Colorado United States 80218
    82 Rocky Mountain Cancer Centers-Midtown Denver Colorado United States 80218
    83 SCL Health Saint Joseph Hospital Denver Colorado United States 80218
    84 Rocky Mountain Cancer Centers-Rose Denver Colorado United States 80220
    85 Rose Medical Center Denver Colorado United States 80220
    86 Western States Cancer Research NCORP Denver Colorado United States 80222
    87 Mercy Medical Center Durango Colorado United States 81301
    88 Shaw Cancer Center Edwards Colorado United States 81632
    89 Mountain Blue Cancer Care Center - Swedish Englewood Colorado United States 80113
    90 Swedish Medical Center Englewood Colorado United States 80113
    91 Poudre Valley Hospital Fort Collins Colorado United States 80524
    92 Mountain Blue Cancer Care Center Golden Colorado United States 80401
    93 Saint Mary's Hospital and Regional Medical Center Grand Junction Colorado United States 81501
    94 North Colorado Medical Center Greeley Colorado United States 80631
    95 Rocky Mountain Cancer Centers-Greenwood Village Greenwood Village Colorado United States 80111
    96 Kaiser Permanente-Rock Creek Lafayette Colorado United States 80026
    97 Rocky Mountain Cancer Centers-Lakewood Lakewood Colorado United States 80228
    98 Saint Anthony Hospital Lakewood Colorado United States 80228
    99 Rocky Mountain Cancer Centers-Littleton Littleton Colorado United States 80120
    100 Littleton Adventist Hospital Littleton Colorado United States 80122
    101 Kaiser Permanente-Lone Tree Lone Tree Colorado United States 80124
    102 Rocky Mountain Cancer Centers-Sky Ridge Lone Tree Colorado United States 80124
    103 Sky Ridge Medical Center Lone Tree Colorado United States 80124
    104 Longmont United Hospital Longmont Colorado United States 80501
    105 Rocky Mountain Cancer Centers-Longmont Longmont Colorado United States 80501
    106 McKee Medical Center Loveland Colorado United States 80539
    107 Parker Adventist Hospital Parker Colorado United States 80138
    108 Rocky Mountain Cancer Centers-Parker Parker Colorado United States 80138
    109 Saint Mary Corwin Medical Center Pueblo Colorado United States 81004
    110 Rocky Mountain Cancer Centers - Pueblo Pueblo Colorado United States 81008
    111 North Suburban Medical Center Thornton Colorado United States 80229
    112 Rocky Mountain Cancer Centers-Thornton Thornton Colorado United States 80260
    113 SCL Health Lutheran Medical Center Wheat Ridge Colorado United States 80033
    114 Hartford Hospital Hartford Connecticut United States 06102
    115 Smilow Cancer Hospital Care Center at Saint Francis Hartford Connecticut United States 06105
    116 Manchester Memorial Hospital Manchester Connecticut United States 06040
    117 The Hospital of Central Connecticut New Britain Connecticut United States 06050
    118 Yale University New Haven Connecticut United States 06520
    119 Eastern Connecticut Hematology and Oncology Associates Norwich Connecticut United States 06360
    120 Stamford Hospital/Bennett Cancer Center Stamford Connecticut United States 06904
    121 Beebe Medical Center Lewes Delaware United States 19958
    122 Christiana Gynecologic Oncology LLC Newark Delaware United States 19713
    123 Delaware Clinical and Laboratory Physicians PA Newark Delaware United States 19713
    124 Helen F Graham Cancer Center Newark Delaware United States 19713
    125 Medical Oncology Hematology Consultants PA Newark Delaware United States 19713
    126 Christiana Care Health System-Christiana Hospital Newark Delaware United States 19718
    127 Beebe Health Campus Rehoboth Beach Delaware United States 19971
    128 Nanticoke Memorial Hospital Seaford Delaware United States 19973
    129 Christiana Care Health System-Wilmington Hospital Wilmington Delaware United States 19801
    130 MedStar Georgetown University Hospital Washington District of Columbia United States 20007
    131 MedStar Washington Hospital Center Washington District of Columbia United States 20010
    132 Sibley Memorial Hospital Washington District of Columbia United States 20016
    133 AdventHealth Altamonte Altamonte Springs Florida United States 32701
    134 Boca Raton Regional Hospital Boca Raton Florida United States 33486
    135 Florida Hospital Memorial Medical Center Daytona Beach Florida United States 32117
    136 Holy Cross Hospital Fort Lauderdale Florida United States 33308
    137 University of Florida Health Science Center - Gainesville Gainesville Florida United States 32610
    138 Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida United States 33021
    139 Baptist MD Anderson Cancer Center Jacksonville Florida United States 32207
    140 Mayo Clinic in Florida Jacksonville Florida United States 32224-9980
    141 Jupiter Medical Center Jupiter Florida United States 33458
    142 AdventHealth Kissimmee Kissimmee Florida United States 34744
    143 Lakeland Regional Health Hollis Cancer Center Lakeland Florida United States 33805
    144 Mount Sinai Medical Center Miami Beach Florida United States 33140
    145 University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida United States 33136
    146 21st Century Oncology-Orange Park Orange Park Florida United States 32073
    147 AdventHealth Orlando Orlando Florida United States 32803
    148 UF Cancer Center at Orlando Health Orlando Florida United States 32806
    149 AdventHealth East Orlando Orlando Florida United States 32822
    150 21st Century Oncology-Palatka Palatka Florida United States 32177
    151 Memorial Hospital West Pembroke Pines Florida United States 33028
    152 Sacred Heart Hospital Pensacola Florida United States 32504
    153 Martin Medical Center Stuart Florida United States 34994
    154 Robert and Carol Weissman Cancer Center at Martin Health Stuart Florida United States 34994
    155 Martin Hospital South Stuart Florida United States 34997
    156 Moffitt Cancer Center Tampa Florida United States 33612
    157 AdventHealth Winter Park Winter Park Florida United States 32792
    158 University Cancer and Blood Center LLC Athens Georgia United States 30607
    159 Emory University Hospital/Winship Cancer Institute Atlanta Georgia United States 30322
    160 Atlanta Regional CCOP Atlanta Georgia United States 30342
    161 Northside Hospital Atlanta Georgia United States 30342
    162 Augusta University Medical Center Augusta Georgia United States 30912
    163 John B Amos Cancer Center Columbus Georgia United States 31904
    164 Northeast Georgia Medical Center-Gainesville Gainesville Georgia United States 30501
    165 Medical Center of Central Georgia Macon Georgia United States 31201
    166 Memorial Health University Medical Center Savannah Georgia United States 31404
    167 Lewis Cancer and Research Pavilion at Saint Joseph's/Candler Savannah Georgia United States 31405
    168 South Georgia Medical Center/Pearlman Cancer Center Valdosta Georgia United States 31602
    169 Pali Momi Medical Center 'Aiea Hawaii United States 96701
    170 Queen's Cancer Center - Pearlridge 'Aiea Hawaii United States 96701
    171 Hawaii Cancer Care Inc-POB II Honolulu Hawaii United States 96813
    172 Queen's Medical Center Honolulu Hawaii United States 96813
    173 Straub Clinic and Hospital Honolulu Hawaii United States 96813
    174 University of Hawaii Cancer Center Honolulu Hawaii United States 96813
    175 Hawaii Cancer Care Inc-Liliha Honolulu Hawaii United States 96817
    176 Kuakini Medical Center Honolulu Hawaii United States 96817
    177 Queen's Cancer Center - Kuakini Honolulu Hawaii United States 96817
    178 Kaiser Permanente Moanalua Medical Center Honolulu Hawaii United States 96819
    179 Kapiolani Medical Center for Women and Children Honolulu Hawaii United States 96826
    180 Castle Medical Center Kailua Hawaii United States 96734
    181 Wilcox Memorial Hospital and Kauai Medical Clinic Lihue Hawaii United States 96766
    182 Saint Alphonsus Cancer Care Center-Boise Boise Idaho United States 83706
    183 Saint Luke's Mountain States Tumor Institute Boise Idaho United States 83712
    184 Saint Luke's Mountain States Tumor Institute - Fruitland Fruitland Idaho United States 83619
    185 Saint Joseph Regional Medical Center Lewiston Idaho United States 83501
    186 Saint Luke's Mountain States Tumor Institute - Meridian Meridian Idaho United States 83642
    187 Saint Luke's Mountain States Tumor Institute - Nampa Nampa Idaho United States 83686
    188 Kootenai Cancer Center Post Falls Idaho United States 83854
    189 Saint Luke's Mountain States Tumor Institute-Twin Falls Twin Falls Idaho United States 83301
    190 Saint Anthony's Health Alton Illinois United States 62002
    191 Rush - Copley Medical Center Aurora Illinois United States 60504
    192 Mac Neal Hospital Berwyn Illinois United States 60402
    193 Saint Joseph Medical Center Bloomington Illinois United States 61701
    194 Illinois CancerCare-Bloomington Bloomington Illinois United States 61704
    195 Graham Hospital Association Canton Illinois United States 61520
    196 Illinois CancerCare-Canton Canton Illinois United States 61520
    197 Memorial Hospital of Carbondale Carbondale Illinois United States 62902
    198 Illinois CancerCare-Carthage Carthage Illinois United States 62321
    199 Memorial Hospital Carthage Illinois United States 62321
    200 Centralia Oncology Clinic Centralia Illinois United States 62801
    201 Hematology and Oncology Associates Chicago Illinois United States 60611
    202 Northwestern University Chicago Illinois United States 60611
    203 Rush University Medical Center Chicago Illinois United States 60612
    204 University of Illinois Chicago Illinois United States 60612
    205 Presence Resurrection Medical Center Chicago Illinois United States 60631
    206 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    207 Weiss Memorial Hospital Chicago Illinois United States 60640
    208 Advocate Illinois Masonic Medical Center Chicago Illinois United States 60657
    209 Presence Saint Joseph Hospital-Chicago Chicago Illinois United States 60657
    210 Carle on Vermilion Danville Illinois United States 61832
    211 Cancer Care Specialists of Illinois - Decatur Decatur Illinois United States 62526
    212 Decatur Memorial Hospital Decatur Illinois United States 62526
    213 Heartland Cancer Research NCORP Decatur Illinois United States 62526
    214 Good Samaritan Hospital Downers Grove Illinois United States 60515
    215 Carle Physician Group-Effingham Effingham Illinois United States 62401
    216 Crossroads Cancer Center Effingham Illinois United States 62401
    217 Advocate Sherman Hospital Elgin Illinois United States 60123
    218 AMITA Health Alexian Brothers Medical Center Elk Grove Village Illinois United States 60007
    219 Eureka Hospital Eureka Illinois United States 61530
    220 Illinois CancerCare-Eureka Eureka Illinois United States 61530
    221 NorthShore University HealthSystem-Evanston Hospital Evanston Illinois United States 60201
    222 Illinois CancerCare-Galesburg Galesburg Illinois United States 61401
    223 Western Illinois Cancer Treatment Center Galesburg Illinois United States 61401
    224 Northwestern Medicine Cancer Center Delnor Geneva Illinois United States 60134
    225 Ingalls Memorial Hospital Harvey Illinois United States 60426
    226 Illinois CancerCare-Havana Havana Illinois United States 62644
    227 Mason District Hospital Havana Illinois United States 62644
    228 Hematology Oncology Associates of Illinois-Highland Park Highland Park Illinois United States 60035
    229 Edward Hines Jr VA Hospital Hines Illinois United States 60141
    230 Hinsdale Hematology Oncology Associates Incorporated Hinsdale Illinois United States 60521
    231 Presence Saint Mary's Hospital Kankakee Illinois United States 60901
    232 Illinois CancerCare-Kewanee Clinic Kewanee Illinois United States 61443
    233 AMG Libertyville - Oncology Libertyville Illinois United States 60048
    234 Illinois CancerCare-Macomb Macomb Illinois United States 61455
    235 Mcdonough District Hospital Macomb Illinois United States 61455
    236 Carle Physician Group-Mattoon/Charleston Mattoon Illinois United States 61938
    237 Loyola University Medical Center Maywood Illinois United States 60153
    238 Garneau, Stewart C MD (UIA Investigator) Moline Illinois United States 61265
    239 Porubcin, Michael MD (UIA Investigator) Moline Illinois United States 61265
    240 Spector, David MD (UIA Investigator) Moline Illinois United States 61265
    241 Trinity Medical Center Moline Illinois United States 61265
    242 Holy Family Medical Center Monmouth Illinois United States 61462
    243 Illinois CancerCare-Monmouth Monmouth Illinois United States 61462
    244 Good Samaritan Regional Health Center Mount Vernon Illinois United States 62864
    245 UC Comprehensive Cancer Center at Silver Cross New Lenox Illinois United States 60451
    246 Illinois Cancer Specialists-Niles Niles Illinois United States 60714
    247 Bromenn Regional Medical Center Normal Illinois United States 61761
    248 Community Cancer Center Foundation Normal Illinois United States 61761
    249 Illinois CancerCare-Community Cancer Center Normal Illinois United States 61761
    250 Mid-Illinois Hematology Oncology Associates Limited Normal Illinois United States 61761
    251 Advocate Christ Medical Center Oak Lawn Illinois United States 60453-2699
    252 Illinois CancerCare-Ottawa Clinic Ottawa Illinois United States 61350
    253 Ottawa Regional Hospital and Healthcare Center Ottawa Illinois United States 61350
    254 Radiation Oncology of Northern Illinois Ottawa Illinois United States 61350
    255 Illinois CancerCare-Pekin Pekin Illinois United States 61554
    256 OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center Pekin Illinois United States 61554
    257 Proctor Hospital Peoria Illinois United States 61614
    258 Illinois CancerCare-Peoria Peoria Illinois United States 61615
    259 OSF Saint Francis Radiation Oncology at Peoria Cancer Center Peoria Illinois United States 61615
    260 Methodist Medical Center of Illinois Peoria Illinois United States 61636
    261 OSF Saint Francis Medical Center Peoria Illinois United States 61637
    262 Illinois CancerCare-Peru Peru Illinois United States 61354
    263 Illinois Valley Hospital Peru Illinois United States 61354
    264 Valley Radiation Oncology Peru Illinois United States 61354
    265 Illinois CancerCare-Princeton Princeton Illinois United States 61356
    266 Perry Memorial Hospital Princeton Illinois United States 61356
    267 West Suburban Medical Center River Forest Illinois United States 60305
    268 Swedish American Hospital Rockford Illinois United States 61104
    269 OSF Saint Anthony Medical Center Rockford Illinois United States 61108
    270 SwedishAmerican Regional Cancer Center/ACT Rockford Illinois United States 61114
    271 Hematology Oncology Associates of Illinois - Skokie Skokie Illinois United States 60076
    272 Illinois CancerCare-Spring Valley Spring Valley Illinois United States 61362
    273 Central Illinois Hematology Oncology Center Springfield Illinois United States 62702
    274 Southern Illinois University School of Medicine Springfield Illinois United States 62702
    275 Springfield Clinic Springfield Illinois United States 62702
    276 Memorial Medical Center Springfield Illinois United States 62781
    277 Carle Cancer Center Urbana Illinois United States 61801
    278 The Carle Foundation Hospital Urbana Illinois United States 61801
    279 Northwestern Medicine Cancer Center Warrenville Warrenville Illinois United States 60555
    280 Rush-Copley Healthcare Center Yorkville Illinois United States 60560
    281 Franciscan Saint Francis Health-Beech Grove Beech Grove Indiana United States 46107
    282 Elkhart Clinic Elkhart Indiana United States 46514-2098
    283 Michiana Hematology Oncology PC-Elkhart Elkhart Indiana United States 46514
    284 Elkhart General Hospital Elkhart Indiana United States 46515
    285 Fort Wayne Medical Oncology and Hematology Inc-Parkview Fort Wayne Indiana United States 46845
    286 Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    287 Community Cancer Center East Indianapolis Indiana United States 46219
    288 Franciscan Health Indianapolis Indianapolis Indiana United States 46237
    289 Community Cancer Center North Indianapolis Indiana United States 46256
    290 Community Howard Regional Health Kokomo Indiana United States 46904
    291 IU Health La Porte Hospital La Porte Indiana United States 46350
    292 Franciscan Saint Anthony Health-Michigan City Michigan City Indiana United States 46360
    293 Woodland Cancer Care Center Michigan City Indiana United States 46360
    294 Michiana Hematology Oncology PC-Mishawaka Mishawaka Indiana United States 46545
    295 Saint Joseph Regional Medical Center-Mishawaka Mishawaka Indiana United States 46545
    296 IU Health Ball Memorial Hospital Muncie Indiana United States 47303
    297 The Community Hospital Munster Indiana United States 46321
    298 Michiana Hematology Oncology PC-Plymouth Plymouth Indiana United States 46563
    299 Reid Health Richmond Indiana United States 47374
    300 Memorial Hospital of South Bend South Bend Indiana United States 46601
    301 Northern Indiana Cancer Research Consortium South Bend Indiana United States 46628
    302 Michiana Hematology Oncology PC-Westville Westville Indiana United States 46391
    303 Mary Greeley Medical Center Ames Iowa United States 50010
    304 McFarland Clinic PC - Ames Ames Iowa United States 50010
    305 Constantinou, Costas L MD (UIA Investigator) Bettendorf Iowa United States 52722
    306 McFarland Clinic PC-Boone Boone Iowa United States 50036
    307 Physicians' Clinic of Iowa PC Cedar Rapids Iowa United States 52402
    308 Saint Luke's Hospital Cedar Rapids Iowa United States 52402
    309 Mercy Hospital Cedar Rapids Iowa United States 52403
    310 Oncology Associates at Mercy Medical Center Cedar Rapids Iowa United States 52403
    311 Medical Oncology and Hematology Associates-West Des Moines Clive Iowa United States 50325
    312 Mercy Cancer Center-West Lakes Clive Iowa United States 50325
    313 Alegent Health Mercy Hospital Council Bluffs Iowa United States 51503
    314 Iowa Methodist Medical Center Des Moines Iowa United States 50309
    315 Iowa-Wide Oncology Research Coalition NCORP Des Moines Iowa United States 50309
    316 Medical Oncology and Hematology Associates-Des Moines Des Moines Iowa United States 50309
    317 Medical Oncology and Hematology Associates-Laurel Des Moines Iowa United States 50314
    318 Mercy Medical Center - Des Moines Des Moines Iowa United States 50314
    319 Iowa Lutheran Hospital Des Moines Iowa United States 50316
    320 McFarland Clinic PC-Trinity Cancer Center Fort Dodge Iowa United States 50501
    321 University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa United States 52242
    322 McFarland Clinic PC-Jefferson Jefferson Iowa United States 50129
    323 McFarland Clinic PC-Marshalltown Marshalltown Iowa United States 50158
    324 Siouxland Regional Cancer Center Sioux City Iowa United States 51101
    325 Mercy Medical Center-Sioux City Sioux City Iowa United States 51102
    326 Saint Luke's Regional Medical Center Sioux City Iowa United States 51104
    327 MercyOne Waterloo Medical Center Waterloo Iowa United States 50702
    328 Methodist West Hospital West Des Moines Iowa United States 50266-7700
    329 Mercy Medical Center-West Lakes West Des Moines Iowa United States 50266
    330 Cancer Center of Kansas - Chanute Chanute Kansas United States 66720
    331 Cancer Center of Kansas - Dodge City Dodge City Kansas United States 67801
    332 Cancer Center of Kansas - El Dorado El Dorado Kansas United States 67042
    333 Newman Regional Health Emporia Kansas United States 66801
    334 Cancer Center of Kansas - Fort Scott Fort Scott Kansas United States 66701
    335 Saint Catherine Hospital Garden City Kansas United States 67846
    336 Saint Rose Ambulatory and Surgery Center Great Bend Kansas United States 67530
    337 HaysMed University of Kansas Health System Hays Kansas United States 67601
    338 Hutchinson Regional Medical Center Hutchinson Kansas United States 67502
    339 Cancer Center of Kansas-Independence Independence Kansas United States 67301
    340 University of Kansas Cancer Center-West Kansas City Kansas United States 66112
    341 University of Kansas Cancer Center Kansas City Kansas United States 66160
    342 Cancer Center of Kansas-Kingman Kingman Kansas United States 67068
    343 Lawrence Memorial Hospital Lawrence Kansas United States 66044
    344 Cancer Center of Kansas-Liberal Liberal Kansas United States 67905
    345 Cancer Center of Kansas-Manhattan Manhattan Kansas United States 66502
    346 Cancer Center of Kansas - McPherson McPherson Kansas United States 67460
    347 Cancer Center of Kansas - Newton Newton Kansas United States 67114
    348 Menorah Medical Center Overland Park Kansas United States 66209
    349 University of Kansas Cancer Center-Overland Park Overland Park Kansas United States 66210
    350 Saint Luke's South Hospital Overland Park Kansas United States 66213
    351 Cancer Center of Kansas - Parsons Parsons Kansas United States 67357
    352 Ascension Via Christi - Pittsburg Pittsburg Kansas United States 66762
    353 Kansas City NCI Community Oncology Research Program Prairie Village Kansas United States 66208
    354 Cancer Center of Kansas - Pratt Pratt Kansas United States 67124
    355 Cancer Center of Kansas - Salina Salina Kansas United States 67401
    356 Salina Regional Health Center Salina Kansas United States 67401
    357 Cotton O'Neil Cancer Center / Stormont Vail Health Topeka Kansas United States 66606
    358 University of Kansas Health System Saint Francis Campus Topeka Kansas United States 66606
    359 Cancer Center of Kansas - Wellington Wellington Kansas United States 67152
    360 Associates In Womens Health Wichita Kansas United States 67208
    361 Cancer Center of Kansas-Wichita Medical Arts Tower Wichita Kansas United States 67208
    362 Ascension Via Christi Hospitals Wichita Wichita Kansas United States 67214
    363 Cancer Center of Kansas - Wichita Wichita Kansas United States 67214
    364 Wesley Medical Center Wichita Kansas United States 67214
    365 Wichita NCI Community Oncology Research Program Wichita Kansas United States 67214
    366 Cancer Center of Kansas - Winfield Winfield Kansas United States 67156
    367 Oncology Hematology Care Inc-Crestview Crestview Hills Kentucky United States 41017
    368 Saint Joseph Radiation Oncology Resource Center Lexington Kentucky United States 40504
    369 University of Kentucky/Markey Cancer Center Lexington Kentucky United States 40536
    370 Jewish Hospital Louisville Kentucky United States 40202
    371 Owensboro Health Mitchell Memorial Cancer Center Owensboro Kentucky United States 42303
    372 Mary Bird Perkins Cancer Center Baton Rouge Louisiana United States 70809
    373 Ochsner Health Center-Summa Baton Rouge Louisiana United States 70809
    374 Ochsner Health Center-Covington Covington Louisiana United States 70433
    375 Ochsner LSU Health Monroe Medical Center Monroe Louisiana United States 71202
    376 Louisiana State University Health Science Center New Orleans Louisiana United States 70112
    377 University Medical Center New Orleans New Orleans Louisiana United States 70112
    378 Ochsner Baptist Medical Center New Orleans Louisiana United States 70115
    379 Ochsner Medical Center Jefferson New Orleans Louisiana United States 70121
    380 LSU Health Sciences Center at Shreveport Shreveport Louisiana United States 71103
    381 Harold Alfond Center for Cancer Care Augusta Maine United States 04330
    382 Eastern Maine Medical Center Bangor Maine United States 04401
    383 Lafayette Family Cancer Center-EMMC Brewer Maine United States 04412
    384 Penobscot Bay Medical Center Rockport Maine United States 04856
    385 Maine Center for Cancer Medicine-Scarborough Scarborough Maine United States 04074
    386 York Hospital York Maine United States 03909
    387 Greater Baltimore Medical Center Baltimore Maryland United States 21204
    388 Sinai Hospital of Baltimore Baltimore Maryland United States 21215
    389 Saint Agnes Hospital Baltimore Maryland United States 21229
    390 MedStar Franklin Square Medical Center/Weinberg Cancer Institute Baltimore Maryland United States 21237
    391 Union Hospital of Cecil County Elkton Maryland United States 21921
    392 Frederick Memorial Hospital Frederick Maryland United States 21701
    393 Northwest Hospital Center Randallstown Maryland United States 21133
    394 Maryland Oncology Hematology PA-Aquilino Cancer Center Rockville Maryland United States 20850
    395 Peninsula Regional Medical Center Salisbury Maryland United States 21801
    396 Tufts Medical Center Boston Massachusetts United States 02111
    397 Massachusetts General Hospital Cancer Center Boston Massachusetts United States 02114
    398 Brigham and Women's Hospital Boston Massachusetts United States 02115
    399 Boston Medical Center Boston Massachusetts United States 02118
    400 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    401 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    402 Lahey Hospital and Medical Center Burlington Massachusetts United States 01805
    403 Mass General/North Shore Cancer Center Danvers Massachusetts United States 01923
    404 Berkshire Medical Center - Cancer Center Pittsfield Massachusetts United States 01201
    405 Baystate Medical Center Springfield Massachusetts United States 01199
    406 UMass Memorial Medical Center - University Campus Worcester Massachusetts United States 01655
    407 Bixby Medical Center Adrian Michigan United States 49221
    408 Hickman Cancer Center Adrian Michigan United States 49221
    409 Michigan Cancer Research Consortium NCORP Ann Arbor Michigan United States 48106
    410 Saint Joseph Mercy Hospital Ann Arbor Michigan United States 48106
    411 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48109
    412 Bronson Battle Creek Battle Creek Michigan United States 49017
    413 Spectrum Health Big Rapids Hospital Big Rapids Michigan United States 49307
    414 McLaren Cancer Institute-Clarkston Clarkston Michigan United States 48346
    415 Beaumont Hospital - Dearborn Dearborn Michigan United States 48124
    416 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    417 Henry Ford Hospital Detroit Michigan United States 48202
    418 Ascension Saint John Hospital Detroit Michigan United States 48236
    419 Green Bay Oncology - Escanaba Escanaba Michigan United States 49829
    420 Beaumont Hospital - Farmington Hills Farmington Hills Michigan United States 48336
    421 Genesys Hurley Cancer Institute Flint Michigan United States 48503
    422 Hurley Medical Center Flint Michigan United States 48503
    423 Genesys Regional Medical Center-West Flint Campus Flint Michigan United States 48532
    424 McLaren Cancer Institute-Flint Flint Michigan United States 48532
    425 Singh and Arora Hematology Oncology PC Flint Michigan United States 48532
    426 Genesys Regional Medical Center Grand Blanc Michigan United States 48439
    427 Cancer Research Consortium of West Michigan NCORP Grand Rapids Michigan United States 49503
    428 Mercy Health Saint Mary's Grand Rapids Michigan United States 49503
    429 Spectrum Health at Butterworth Campus Grand Rapids Michigan United States 49503
    430 Green Bay Oncology - Iron Mountain Iron Mountain Michigan United States 49801
    431 Allegiance Health Jackson Michigan United States 49201
    432 West Michigan Cancer Center Kalamazoo Michigan United States 49007
    433 Sparrow Hospital Lansing Michigan United States 48912
    434 McLaren Cancer Institute-Lapeer Region Lapeer Michigan United States 48446
    435 Saint Mary Mercy Hospital Livonia Michigan United States 48154
    436 UP Health System Marquette Marquette Michigan United States 49855
    437 Mercy Memorial Hospital Monroe Michigan United States 48162
    438 Toledo Clinic Cancer Centers-Monroe Monroe Michigan United States 48162
    439 McLaren Cancer Institute-Macomb Mount Clemens Michigan United States 48043
    440 Mercy Health Mercy Campus Muskegon Michigan United States 49444
    441 Lakeland Hospital Niles Niles Michigan United States 49120
    442 McLaren Cancer Institute-Northern Michigan Petoskey Michigan United States 49770
    443 Saint Joseph Mercy Oakland Pontiac Michigan United States 48341
    444 Lake Huron Medical Center Port Huron Michigan United States 48060
    445 Spectrum Health Reed City Hospital Reed City Michigan United States 49677
    446 William Beaumont Hospital-Royal Oak Royal Oak Michigan United States 48073
    447 Ascension Saint Mary's Hospital Saginaw Michigan United States 48601
    448 Lakeland Medical Center Saint Joseph Saint Joseph Michigan United States 49085
    449 Marie Yeager Cancer Center Saint Joseph Michigan United States 49085
    450 Munson Medical Center Traverse City Michigan United States 49684
    451 William Beaumont Hospital - Troy Troy Michigan United States 48085
    452 Saint John Macomb-Oakland Hospital Warren Michigan United States 48093
    453 Sanford Joe Lueken Cancer Center Bemidji Minnesota United States 56601
    454 Essentia Health Saint Joseph's Medical Center Brainerd Minnesota United States 56401
    455 Fairview Ridges Hospital Burnsville Minnesota United States 55337
    456 Mercy Hospital Coon Rapids Minnesota United States 55433
    457 Essentia Health Cancer Center Duluth Minnesota United States 55805
    458 Essentia Health Saint Mary's Medical Center Duluth Minnesota United States 55805
    459 Miller-Dwan Hospital Duluth Minnesota United States 55805
    460 Fairview Southdale Hospital Edina Minnesota United States 55435
    461 Unity Hospital Fridley Minnesota United States 55432
    462 Hutchinson Area Health Care Hutchinson Minnesota United States 55350
    463 Minnesota Oncology Hematology PA-Maplewood Maplewood Minnesota United States 55109
    464 Saint John's Hospital - Healtheast Maplewood Minnesota United States 55109
    465 Abbott-Northwestern Hospital Minneapolis Minnesota United States 55407
    466 Hennepin County Medical Center Minneapolis Minnesota United States 55415
    467 Health Partners Inc Minneapolis Minnesota United States 55454
    468 New Ulm Medical Center New Ulm Minnesota United States 56073
    469 North Memorial Medical Health Center Robbinsdale Minnesota United States 55422
    470 Coborn Cancer Center at Saint Cloud Hospital Saint Cloud Minnesota United States 56303
    471 Saint Cloud Hospital Saint Cloud Minnesota United States 56303
    472 Metro Minnesota Community Oncology Research Consortium Saint Louis Park Minnesota United States 55416
    473 Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota United States 55416
    474 Regions Hospital Saint Paul Minnesota United States 55101
    475 United Hospital Saint Paul Minnesota United States 55102
    476 Saint Francis Regional Medical Center Shakopee Minnesota United States 55379
    477 Lakeview Hospital Stillwater Minnesota United States 55082
    478 Ridgeview Medical Center Waconia Minnesota United States 55387
    479 Rice Memorial Hospital Willmar Minnesota United States 56201
    480 Minnesota Oncology Hematology PA-Woodbury Woodbury Minnesota United States 55125
    481 University of Mississippi Medical Center Jackson Mississippi United States 39216
    482 Central Care Cancer Center - Bolivar Bolivar Missouri United States 65613
    483 Parkland Health Center-Bonne Terre Bonne Terre Missouri United States 63628
    484 Cox Cancer Center Branson Branson Missouri United States 65616
    485 Saint Francis Medical Center Cape Girardeau Missouri United States 63703
    486 Southeast Cancer Center Cape Girardeau Missouri United States 63703
    487 Veterans Administration Columbia Missouri United States 65201
    488 University of Missouri - Ellis Fischel Columbia Missouri United States 65212
    489 Centerpoint Medical Center LLC Independence Missouri United States 64057
    490 Capital Region Southwest Campus Jefferson City Missouri United States 65109
    491 Freeman Health System Joplin Missouri United States 64804
    492 Truman Medical Centers Kansas City Missouri United States 64108
    493 Saint Luke's Hospital of Kansas City Kansas City Missouri United States 64111
    494 Heartland Hematology and Oncology Associates Incorporated Kansas City Missouri United States 64118
    495 The University of Kansas Cancer Center-South Kansas City Missouri United States 64131
    496 Research Medical Center Kansas City Missouri United States 64132
    497 University of Kansas Cancer Center - North Kansas City Missouri United States 64154
    498 University of Kansas Cancer Center - Lee's Summit Lee's Summit Missouri United States 64064
    499 Saint Luke's East - Lee's Summit Lee's Summit Missouri United States 64086
    500 Liberty Radiation Oncology Center Liberty Missouri United States 64068
    501 Delbert Day Cancer Institute at PCRMC Rolla Missouri United States 65401
    502 Mercy Clinic-Rolla-Cancer and Hematology Rolla Missouri United States 65401
    503 Heartland Regional Medical Center Saint Joseph Missouri United States 64506
    504 Saint Louis Cancer and Breast Institute-South City Saint Louis Missouri United States 63109
    505 Washington University School of Medicine Saint Louis Missouri United States 63110
    506 Missouri Baptist Medical Center Saint Louis Missouri United States 63131
    507 Mercy Hospital Saint Louis Saint Louis Missouri United States 63141
    508 Saint Louis-Cape Girardeau CCOP Saint Louis Missouri United States 63141
    509 Sainte Genevieve County Memorial Hospital Sainte Genevieve Missouri United States 63670
    510 Cancer Research for the Ozarks NCORP Springfield Missouri United States 65804
    511 Mercy Hospital Springfield Springfield Missouri United States 65804
    512 CoxHealth South Hospital Springfield Missouri United States 65807
    513 Missouri Baptist Sullivan Hospital Sullivan Missouri United States 63080
    514 Missouri Baptist Outpatient Center-Sunset Hills Sunset Hills Missouri United States 63127
    515 Billings Clinic Cancer Center Billings Montana United States 59101
    516 Saint Vincent Healthcare Billings Montana United States 59101
    517 Montana Cancer Consortium NCORP Billings Montana United States 59102
    518 Bozeman Deaconess Hospital Bozeman Montana United States 59715
    519 Saint James Community Hospital and Cancer Treatment Center Butte Montana United States 59701
    520 Benefis Healthcare- Sletten Cancer Institute Great Falls Montana United States 59405
    521 Saint Peter's Community Hospital Helena Montana United States 59601
    522 Kalispell Regional Medical Center Kalispell Montana United States 59901
    523 Saint Patrick Hospital - Community Hospital Missoula Montana United States 59802
    524 CHI Health Saint Francis Grand Island Nebraska United States 68803
    525 Heartland Hematology and Oncology Kearney Nebraska United States 68845
    526 CHI Health Good Samaritan Kearney Nebraska United States 68847
    527 Nebraska Hematology and Oncology Lincoln Nebraska United States 68506
    528 Nebraska Cancer Research Center Lincoln Nebraska United States 68510
    529 Saint Elizabeth Regional Medical Center Lincoln Nebraska United States 68510
    530 Southeast Nebraska Cancer Center - 68th Street Place Lincoln Nebraska United States 68516
    531 Missouri Valley Cancer Consortium Omaha Nebraska United States 68106
    532 Nebraska Methodist Hospital Omaha Nebraska United States 68114
    533 Alegent Health Immanuel Medical Center Omaha Nebraska United States 68122
    534 Hematology and Oncology Consultants PC Omaha Nebraska United States 68122
    535 Alegent Health Bergan Mercy Medical Center Omaha Nebraska United States 68124
    536 Nebraska Cancer Specialists - Omaha Omaha Nebraska United States 68124
    537 Alegent Health Lakeside Hospital Omaha Nebraska United States 68130
    538 Creighton University Medical Center Omaha Nebraska United States 68131
    539 University of Nebraska Medical Center Omaha Nebraska United States 68198
    540 Midlands Community Hospital Papillion Nebraska United States 68046
    541 Regional West Medical Center Cancer Center Scottsbluff Nebraska United States 69361
    542 Cancer and Blood Specialists-Henderson Henderson Nevada United States 89052
    543 Comprehensive Cancer Centers of Nevada - Henderson Henderson Nevada United States 89052
    544 Las Vegas Cancer Center-Henderson Henderson Nevada United States 89052
    545 21st Century Oncology-Henderson Henderson Nevada United States 89074
    546 Comprehensive Cancer Centers of Nevada-Southeast Henderson Henderson Nevada United States 89074
    547 University Medical Center of Southern Nevada Las Vegas Nevada United States 89102
    548 Cancer and Blood Specialists-Shadow Las Vegas Nevada United States 89106
    549 Nevada Cancer Research Foundation CCOP Las Vegas Nevada United States 89106
    550 Radiation Oncology Centers of Nevada Central Las Vegas Nevada United States 89106
    551 21st Century Oncology Las Vegas Nevada United States 89109
    552 HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway Las Vegas Nevada United States 89109
    553 HealthCare Partners Medical Group Oncology/Hematology-San Martin Las Vegas Nevada United States 89113
    554 Radiation Oncology Centers of Nevada Southeast Las Vegas Nevada United States 89119
    555 Cancer Therapy and Integrative Medicine Las Vegas Nevada United States 89121
    556 21st Century Oncology-Vegas Tenaya Las Vegas Nevada United States 89128
    557 Cancer and Blood Specialists-Tenaya Las Vegas Nevada United States 89128
    558 Comprehensive Cancer Centers of Nevada - Northwest Las Vegas Nevada United States 89128
    559 HealthCare Partners Medical Group Oncology/Hematology-Tenaya Las Vegas Nevada United States 89128
    560 Alliance for Childhood Diseases/Cure 4 the Kids Foundation Las Vegas Nevada United States 89135
    561 Comprehensive Cancer Centers of Nevada-Summerlin Las Vegas Nevada United States 89144
    562 Summerlin Hospital Medical Center Las Vegas Nevada United States 89144
    563 Las Vegas Cancer Center-Medical Center Las Vegas Nevada United States 89148-2405
    564 21st Century Oncology-Fort Apache Las Vegas Nevada United States 89148
    565 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89148
    566 OptumCare Cancer Care at Fort Apache Las Vegas Nevada United States 89148
    567 HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills Las Vegas Nevada United States 89149
    568 Comprehensive Cancer Centers of Nevada - Central Valley Las Vegas Nevada United States 89169
    569 Renown Regional Medical Center Reno Nevada United States 89502
    570 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
    571 Portsmouth Regional Hospital Portsmouth New Hampshire United States 03802
    572 Cooper Hospital University Medical Center Camden New Jersey United States 08103
    573 Veterans Adminstration New Jersey Health Care System East Orange New Jersey United States 07018-1095
    574 Hunterdon Medical Center Flemington New Jersey United States 08822
    575 Hackensack University Medical Center Hackensack New Jersey United States 07601
    576 The Cancer Institute of New Jersey Hamilton Hamilton New Jersey United States 08690
    577 Saint Barnabas Medical Center Livingston New Jersey United States 07039
    578 Morristown Medical Center Morristown New Jersey United States 07960
    579 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08903
    580 Overlook Hospital Summit New Jersey United States 07902
    581 Inspira Medical Center Vineland Vineland New Jersey United States 08360
    582 MD Anderson Cancer Center at Cooper-Voorhees Voorhees New Jersey United States 08043
    583 University of New Mexico Cancer Center Albuquerque New Mexico United States 87102
    584 Presbyterian Kaseman Hospital Albuquerque New Mexico United States 87110
    585 New York Oncology Hematology PC - Albany Albany New York United States 12206
    586 New York Oncology Hematology PC - Albany Medical Center Albany New York United States 12208
    587 New York Oncology Hematology PC - Amsterdam Amsterdam New York United States 12010
    588 Hematology Oncology Associates of Central New York-Auburn Auburn New York United States 13021
    589 Montefiore Medical Center-Weiler Hospital Bronx New York United States 10461
    590 Montefiore Medical Center - Moses Campus Bronx New York United States 10467
    591 New York Oncology Hematology PC - Clifton Park Clifton Park New York United States 12065
    592 Mary Imogene Bassett Hospital Cooperstown New York United States 13326
    593 Hematology Oncology Associates of Central New York-East Syracuse East Syracuse New York United States 13057
    594 Glens Falls Hospital Glens Falls New York United States 12801
    595 New York Oncology Hematology PC-Hudson Hudson New York United States 12534
    596 Northwell Health NCORP Lake Success New York United States 11042
    597 Northwell Health/Center for Advanced Medicine Lake Success New York United States 11042
    598 Hematology Oncology Associates of Central New York-Liverpool Liverpool New York United States 13088
    599 North Shore University Hospital Manhasset New York United States 11030
    600 Orange Regional Medical Center Middletown New York United States 10940
    601 Long Island Jewish Medical Center New Hyde Park New York United States 11040
    602 Mount Sinai Union Square New York New York United States 10003
    603 Mount Sinai West New York New York United States 10019
    604 NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York United States 10032
    605 MidHudson Regional Hospital of Westchester Medical Center Poughkeepsie New York United States 12601
    606 University of Rochester Rochester New York United States 14642
    607 Hematology Oncology Associates of Central New York-Rome Rome New York United States 13440
    608 Stony Brook University Medical Center Stony Brook New York United States 11794
    609 State University of New York Upstate Medical University Syracuse New York United States 13210
    610 Hematology Oncology Associates of Central New York-Onondaga Hill Syracuse New York United States 13215
    611 New York Oncology Hematology PC - Troy Troy New York United States 12180
    612 Faxton-Saint Luke's Healthcare Utica New York United States 13502
    613 Atrium Health Stanly/LCI-Albemarle Albemarle North Carolina United States 28002
    614 Randolph Hospital Asheboro North Carolina United States 27203
    615 Mission Hospital Asheville North Carolina United States 28801
    616 Mountain Radiation Oncology PA Asheville North Carolina United States 28801
    617 AdventHealth Infusion Center Asheville Asheville North Carolina United States 28803
    618 Messino Cancer Centers Asheville North Carolina United States 28806
    619 Hope Women's Cancer Centers-Asheville Asheville North Carolina United States 28816
    620 Transylvania Regional Hospital Brevard North Carolina United States 28712
    621 UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27599
    622 Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina United States 28203
    623 Novant Health Presbyterian Medical Center Charlotte North Carolina United States 28204
    624 Sampson Radiation Oncology Clinton North Carolina United States 28328
    625 Southeastern Medical Oncology Center-Clinton Clinton North Carolina United States 28328
    626 Atrium Health Cabarrus/LCI-Concord Concord North Carolina United States 28025
    627 Duke University Medical Center Durham North Carolina United States 27710
    628 Angel Medical Center Franklin North Carolina United States 28734
    629 Southeastern Medical Oncology Center-Goldsboro Goldsboro North Carolina United States 27534
    630 Wayne Memorial Hospital Goldsboro North Carolina United States 27534
    631 Wayne Radiation Oncology Goldsboro North Carolina United States 27534
    632 Cone Health Cancer Center Greensboro North Carolina United States 27403
    633 East Carolina University Greenville North Carolina United States 27834
    634 Onslow Memorial Hospital Jacksonville North Carolina United States 28546
    635 Southeastern Medical Oncology Center-Jacksonville Jacksonville North Carolina United States 28546
    636 Vidant Oncology-Kinston Kinston North Carolina United States 28501
    637 Mission Hospital McDowell Marion North Carolina United States 28752
    638 Atrium Health Union/LCI-Union Monroe North Carolina United States 28112
    639 Annie Penn Memorial Hospital Reidsville North Carolina United States 27320
    640 Rutherford Hospital Rutherfordton North Carolina United States 28139
    641 Blue Ridge Regional Hospital Spruce Pine North Carolina United States 28777
    642 Iredell Memorial Hospital Statesville North Carolina United States 28677
    643 Southeast Clinical Oncology Research Consortium NCORP Winston-Salem North Carolina United States 27104
    644 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    645 Mid Dakota Clinic Bismarck North Dakota United States 58501
    646 Saint Alexius Medical Center Bismarck North Dakota United States 58501
    647 Sanford Bismarck Medical Center Bismarck North Dakota United States 58501
    648 Sanford Broadway Medical Center Fargo North Dakota United States 58122
    649 Sanford Clinic North-Fargo Fargo North Dakota United States 58122
    650 Sanford Roger Maris Cancer Center Fargo North Dakota United States 58122
    651 Altru Cancer Center Grand Forks North Dakota United States 58201
    652 Trinity Cancer Care Center Minot North Dakota United States 58701
    653 Summa Health System - Akron Campus Akron Ohio United States 44304
    654 Cleveland Clinic Akron General Akron Ohio United States 44307
    655 Summa Health System - Barberton Campus Barberton Ohio United States 44203
    656 Cleveland Clinic Cancer Center Beachwood Beachwood Ohio United States 44122
    657 Mary Rutan Hospital Bellefontaine Ohio United States 43311
    658 Strecker Cancer Center-Belpre Belpre Ohio United States 45714
    659 Toledo Clinic Cancer Centers-Bowling Green Bowling Green Ohio United States 43402
    660 Aultman Health Foundation Canton Ohio United States 44710
    661 Miami Valley Hospital South Centerville Ohio United States 45459
    662 Adena Regional Medical Center Chillicothe Ohio United States 45601
    663 Oncology Hematology Care Inc-Eden Park Cincinnati Ohio United States 45202
    664 Oncology Hematology Care Inc-Mercy West Cincinnati Ohio United States 45211
    665 The Christ Hospital Cincinnati Ohio United States 45219
    666 University of Cincinnati/Barrett Cancer Center Cincinnati Ohio United States 45219
    667 Good Samaritan Hospital - Cincinnati Cincinnati Ohio United States 45220
    668 Oncology Hematology Care Inc-Anderson Cincinnati Ohio United States 45230
    669 Oncology Hematology Care Inc-Kenwood Cincinnati Ohio United States 45236
    670 Bethesda North Hospital Cincinnati Ohio United States 45242
    671 Oncology Hematology Care Inc-Blue Ash Cincinnati Ohio United States 45242
    672 Case Western Reserve University Cleveland Ohio United States 44106
    673 MetroHealth Medical Center Cleveland Ohio United States 44109
    674 Cleveland Clinic Cancer Center/Fairview Hospital Cleveland Ohio United States 44111
    675 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    676 Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210
    677 Columbus Oncology and Hematology Associates Inc Columbus Ohio United States 43214
    678 Riverside Methodist Hospital Columbus Ohio United States 43214
    679 Columbus NCI Community Oncology Research Program Columbus Ohio United States 43215
    680 Grant Medical Center Columbus Ohio United States 43215
    681 The Mark H Zangmeister Center Columbus Ohio United States 43219
    682 Mount Carmel Health Center West Columbus Ohio United States 43222
    683 Doctors Hospital Columbus Ohio United States 43228
    684 Grandview Hospital Dayton Ohio United States 45405
    685 Good Samaritan Hospital - Dayton Dayton Ohio United States 45406
    686 Miami Valley Hospital Dayton Ohio United States 45409
    687 Miami Valley Hospital North Dayton Ohio United States 45415
    688 Dayton NCI Community Oncology Research Program Dayton Ohio United States 45459
    689 Delaware Health Center-Grady Cancer Center Delaware Ohio United States 43015
    690 Delaware Radiation Oncology Delaware Ohio United States 43015
    691 Grady Memorial Hospital Delaware Ohio United States 43015
    692 Oncology Hematology Care Inc-Healthplex Fairfield Ohio United States 45014
    693 Blanchard Valley Hospital Findlay Ohio United States 45840
    694 Atrium Medical Center-Middletown Regional Hospital Franklin Ohio United States 45005-1066
    695 Wayne Hospital Greenville Ohio United States 45331
    696 Cleveland Clinic Cancer Center Independence Independence Ohio United States 44131
    697 Kettering Medical Center Kettering Ohio United States 45429
    698 Fairfield Medical Center Lancaster Ohio United States 43130
    699 Lancaster Radiation Oncology Lancaster Ohio United States 43130
    700 Lima Memorial Hospital Lima Ohio United States 45804
    701 Marietta Memorial Hospital Marietta Ohio United States 45750
    702 Toledo Clinic Cancer Centers-Maumee Maumee Ohio United States 43537
    703 Toledo Radiation Oncology at Northwest Ohio Onocolgy Center Maumee Ohio United States 43537
    704 Hillcrest Hospital Cancer Center Mayfield Heights Ohio United States 44124
    705 Knox Community Hospital Mount Vernon Ohio United States 43050
    706 Licking Memorial Hospital Newark Ohio United States 43055
    707 Newark Radiation Oncology Newark Ohio United States 43055
    708 Saint Charles Hospital Oregon Ohio United States 43616
    709 Toledo Clinic Cancer Centers-Oregon Oregon Ohio United States 43616
    710 Southern Ohio Medical Center Portsmouth Ohio United States 45662
    711 North Coast Cancer Care Sandusky Ohio United States 44870
    712 Springfield Regional Medical Center Springfield Ohio United States 45505
    713 Cleveland Clinic Cancer Center Strongsville Strongsville Ohio United States 44136
    714 ProMedica Flower Hospital Sylvania Ohio United States 43560
    715 Mercy Hospital of Tiffin Tiffin Ohio United States 44883
    716 ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital Toledo Ohio United States 43606
    717 Saint Vincent Mercy Medical Center Toledo Ohio United States 43608
    718 University of Toledo Toledo Ohio United States 43614
    719 Toledo Community Hospital Oncology Program CCOP Toledo Ohio United States 43617
    720 Mercy Saint Anne Hospital Toledo Ohio United States 43623
    721 Toledo Clinic Cancer Centers-Toledo Toledo Ohio United States 43623
    722 Upper Valley Medical Center Troy Ohio United States 45373
    723 Fulton County Health Center Wauseon Ohio United States 43567
    724 Saint Ann's Hospital Westerville Ohio United States 43081
    725 Cleveland Clinic Wooster Family Health and Surgery Center Wooster Ohio United States 44691
    726 Wright-Patterson Medical Center Wright-Patterson Air Force Base Ohio United States 45433-5529
    727 Greene Memorial Hospital Xenia Ohio United States 45385
    728 Genesis Healthcare System Cancer Care Center Zanesville Ohio United States 43701
    729 Cancer Centers of Southwest Oklahoma Research Lawton Oklahoma United States 73505
    730 Cancer Care Associates-Norman Norman Oklahoma United States 73071
    731 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    732 Integris Southwest Medical Center Oklahoma City Oklahoma United States 73109
    733 Mercy Hospital Oklahoma City Oklahoma City Oklahoma United States 73120
    734 Mercy Physicians of Oklahoma-Lakeside Oklahoma City Oklahoma United States 73120
    735 Integris Cancer Institute of Oklahoma Oklahoma City Oklahoma United States 73142
    736 Oklahoma Cancer Specialists and Research Institute-Tulsa Tulsa Oklahoma United States 74146
    737 Saint Charles Health System Bend Oregon United States 97701
    738 Clackamas Radiation Oncology Center Clackamas Oregon United States 97015
    739 Providence Cancer Institute Clackamas Clinic Clackamas Oregon United States 97015
    740 Bay Area Hospital Coos Bay Oregon United States 97420
    741 Providence Milwaukie Hospital Milwaukie Oregon United States 97222
    742 Providence Newberg Medical Center Newberg Oregon United States 97132
    743 Providence Willamette Falls Medical Center Oregon City Oregon United States 97045
    744 Providence Portland Medical Center Portland Oregon United States 97213
    745 Providence Saint Vincent Medical Center Portland Oregon United States 97225
    746 Kaiser Permanente Northwest Portland Oregon United States 97227
    747 Oregon Health and Science University Portland Oregon United States 97239
    748 Mid-Columbia Medical Center/Celilo Cancer Center The Dalles Oregon United States 97058
    749 Abington Memorial Hospital Abington Pennsylvania United States 19001
    750 Lehigh Valley Hospital-Cedar Crest Allentown Pennsylvania United States 18103
    751 Saint Luke's University Hospital-Bethlehem Campus Bethlehem Pennsylvania United States 18015
    752 Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania United States 18017
    753 Bryn Mawr Hospital Bryn Mawr Pennsylvania United States 19010
    754 Geisinger Medical Center Danville Pennsylvania United States 17822
    755 Delaware County Memorial Hospital Drexel Hill Pennsylvania United States 19026
    756 Pocono Medical Center East Stroudsburg Pennsylvania United States 18301
    757 Geisinger Medical Center-Cancer Center Hazleton Hazleton Pennsylvania United States 18201
    758 Penn State Milton S Hershey Medical Center Hershey Pennsylvania United States 17033-0850
    759 Armstrong Center for Medicine and Health Kittanning Pennsylvania United States 16201
    760 Geisinger Medical Oncology-Lewisburg Lewisburg Pennsylvania United States 17837
    761 Lewistown Hospital Lewistown Pennsylvania United States 17044
    762 Riddle Memorial Hospital Media Pennsylvania United States 19063
    763 Forbes Hospital Monroeville Pennsylvania United States 15146
    764 Allegheny Valley Hospital Natrona Heights Pennsylvania United States 15065
    765 Paoli Memorial Hospital Paoli Pennsylvania United States 19301
    766 University of Pennsylvania/Abramson Cancer Center Philadelphia Pennsylvania United States 19104
    767 Thomas Jefferson University Hospital Philadelphia Pennsylvania United States 19107
    768 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    769 Allegheny General Hospital Pittsburgh Pennsylvania United States 15212
    770 West Penn Hospital Pittsburgh Pennsylvania United States 15224
    771 University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania United States 15232
    772 Geisinger Cancer Services-Pottsville Pottsville Pennsylvania United States 17901
    773 Guthrie Medical Group PC-Robert Packer Hospital Sayre Pennsylvania United States 18840
    774 Mercy Hospital Scranton Pennsylvania United States 18501
    775 Scranton Hematology Oncology Scranton Pennsylvania United States 18510
    776 Geisinger Medical Group State College Pennsylvania United States 16801
    777 Mount Nittany Medical Center State College Pennsylvania United States 16803
    778 Reading Hospital West Reading Pennsylvania United States 19611
    779 Geisinger Wyoming Valley/Henry Cancer Center Wilkes-Barre Pennsylvania United States 18711
    780 UPMC Susquehanna Williamsport Pennsylvania United States 17701
    781 Lankenau Medical Center Wynnewood Pennsylvania United States 19096
    782 Main Line Health NCORP Wynnewood Pennsylvania United States 19096
    783 Rhode Island Hospital Providence Rhode Island United States 02903
    784 Miriam Hospital Providence Rhode Island United States 02906
    785 Roger Williams Medical Center Providence Rhode Island United States 02908
    786 AnMed Health Cancer Center Anderson South Carolina United States 29621
    787 AnMed Health Hospital Anderson South Carolina United States 29621
    788 Roper Hospital Charleston South Carolina United States 29401
    789 Charleston Oncology - Roper Charleston South Carolina United States 29403
    790 Charleston Oncology - Saint Francis Charleston South Carolina United States 29414
    791 Lowcountry Hematology Oncology PA-West Ashley Charleston South Carolina United States 29414
    792 Prisma Health Cancer Institute - Easley Easley South Carolina United States 29640
    793 Saint Francis Hospital Greenville South Carolina United States 29601
    794 Prisma Health Cancer Institute - Butternut Greenville South Carolina United States 29605
    795 Prisma Health Cancer Institute - Faris Greenville South Carolina United States 29605
    796 Prisma Health Greenville Memorial Hospital Greenville South Carolina United States 29605
    797 Prisma Health Cancer Institute - Eastside Greenville South Carolina United States 29615
    798 Prisma Health Cancer Institute - Greer Greer South Carolina United States 29650
    799 Gibbs Cancer Center-Pelham Greer South Carolina United States 29651
    800 Carolina Blood and Cancer Care Associates PA-Lancaster Lancaster South Carolina United States 29720
    801 Lowcountry Hematology Oncology PA-Mount Pleasant Mount Pleasant South Carolina United States 29464
    802 Carolina Blood and Cancer Care Associates PA Rock Hill South Carolina United States 29732
    803 Prisma Health Cancer Institute - Seneca Seneca South Carolina United States 29672
    804 Spartanburg Medical Center Spartanburg South Carolina United States 29303
    805 Prisma Health Cancer Institute - Spartanburg Spartanburg South Carolina United States 29307
    806 Sanford Cancer Center Oncology Clinic Sioux Falls South Dakota United States 57104
    807 Avera Cancer Institute Sioux Falls South Dakota United States 57105
    808 Avera McKennan Hospital and University Health Center Sioux Falls South Dakota United States 57105
    809 Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota United States 57117-5134
    810 Erlanger Medical Center Chattanooga Tennessee United States 37403
    811 Memorial Hospital Chattanooga Tennessee United States 37404
    812 Jackson-Madison County General Hospital Jackson Tennessee United States 38301
    813 Regional Cancer Center at Indian Path Community Hospital Kingsport Tennessee United States 37660
    814 Wellmont Holston Valley Hospital and Medical Center Kingsport Tennessee United States 37660
    815 Thompson Cancer Survival Center Knoxville Tennessee United States 37916
    816 University of Tennessee - Knoxville Knoxville Tennessee United States 37920
    817 Vanderbilt University/Ingram Cancer Center Nashville Tennessee United States 37232
    818 Parkland Memorial Hospital Dallas Texas United States 75235
    819 Baylor University Medical Center Dallas Texas United States 75246
    820 UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas United States 75390
    821 Brooke Army Medical Center Fort Sam Houston Texas United States 78234
    822 Scott and White Memorial Hospital Temple Texas United States 76508
    823 American Fork Hospital / Huntsman Intermountain Cancer Center American Fork Utah United States 84003
    824 Sandra L Maxwell Cancer Center Cedar City Utah United States 84720
    825 Logan Regional Hospital Logan Utah United States 84321
    826 Intermountain Medical Center Murray Utah United States 84107
    827 McKay-Dee Hospital Center Ogden Utah United States 84403
    828 Utah Valley Regional Medical Center Provo Utah United States 84604
    829 Dixie Medical Center Regional Cancer Center Saint George Utah United States 84770
    830 Utah Cancer Specialists-Salt Lake City Salt Lake City Utah United States 84106
    831 Huntsman Cancer Institute/University of Utah Salt Lake City Utah United States 84112
    832 LDS Hospital Salt Lake City Utah United States 84143
    833 Central Vermont Medical Center/National Life Cancer Treatment Berlin Vermont United States 05602
    834 University of Vermont and State Agricultural College Burlington Vermont United States 05405
    835 Fredericksburg Oncology Inc Fredericksburg Virginia United States 22401
    836 Hematology Oncology Associates of Fredericksburg Inc Fredericksburg Virginia United States 22408
    837 Southwest VA Regional Cancer Center Norton Virginia United States 24273
    838 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298
    839 Cancer Care Center at Island Hospital Anacortes Washington United States 98221
    840 MultiCare Auburn Medical Center Auburn Washington United States 98001
    841 Overlake Hospital Medical Center Bellevue Washington United States 98004
    842 PeaceHealth Saint Joseph Medical Center Bellingham Washington United States 98225
    843 Harrison HealthPartners Hematology and Oncology-Bremerton Bremerton Washington United States 98310
    844 Harrison Medical Center Bremerton Washington United States 98310
    845 Highline Medical Center-Main Campus Burien Washington United States 98166
    846 Providence Regional Cancer System-Centralia Centralia Washington United States 98531
    847 Swedish Cancer Institute-Edmonds Edmonds Washington United States 98026
    848 Providence Regional Cancer Partnership Everett Washington United States 98201
    849 Saint Francis Hospital Federal Way Washington United States 98003
    850 Swedish Cancer Institute-Issaquah Issaquah Washington United States 98029
    851 Kadlec Clinic Hematology and Oncology Kennewick Washington United States 99336
    852 Seattle Cancer Care Alliance at EvergreenHealth Kirkland Washington United States 98034
    853 Providence Regional Cancer System-Lacey Lacey Washington United States 98503
    854 Saint Clare Hospital Lakewood Washington United States 98499
    855 PeaceHealth Saint John Medical Center Longview Washington United States 98632
    856 Skagit Valley Hospital Mount Vernon Washington United States 98274
    857 Providence - Saint Peter Hospital Olympia Washington United States 98506-5166
    858 Capital Medical Center Olympia Washington United States 98507
    859 Harrison HealthPartners Hematology and Oncology-Poulsbo Poulsbo Washington United States 98370
    860 MultiCare Good Samaritan Hospital Puyallup Washington United States 98372
    861 Virginia Mason Medical Center Seattle Washington United States 98101
    862 Minor and James Medical PLLC Seattle Washington United States 98104
    863 Pacific Medical Center-First Hill Seattle Washington United States 98104
    864 Swedish Medical Center-Ballard Campus Seattle Washington United States 98107
    865 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109
    866 Kaiser Permanente Washington Seattle Washington United States 98112
    867 Swedish Medical Center-First Hill Seattle Washington United States 98122-4307
    868 University of Washington Medical Center Seattle Washington United States 98195
    869 Cancer Care Northwest - Spokane South Spokane Washington United States 99202
    870 Evergreen Hematology and Oncology PS Spokane Washington United States 99218
    871 Rockwood Clinic Spokane Washington United States 99220
    872 MultiCare Allenmore Hospital Tacoma Washington United States 98405
    873 MultiCare Tacoma General Hospital Tacoma Washington United States 98405
    874 Northwest Medical Specialties PLLC Tacoma Washington United States 98405
    875 Northwest NCI Community Oncology Research Program Tacoma Washington United States 98405
    876 Saint Joseph Medical Center Tacoma Washington United States 98405
    877 PeaceHealth Southwest Medical Center Vancouver Washington United States 98664
    878 Wenatchee Valley Hospital and Clinics Wenatchee Washington United States 98801
    879 West Virginia University Charleston Division Charleston West Virginia United States 25304
    880 Edwards Comprehensive Cancer Center Huntington West Virginia United States 25701
    881 Saint Mary's Medical Center Huntington West Virginia United States 25702
    882 West Virginia University Healthcare Morgantown West Virginia United States 26506
    883 Wheeling Hospital/Schiffler Cancer Center Wheeling West Virginia United States 26003
    884 Langlade Hospital and Cancer Center Antigo Wisconsin United States 54409
    885 ThedaCare Regional Cancer Center Appleton Wisconsin United States 54911
    886 Aurora Cancer Care-Southern Lakes VLCC Burlington Wisconsin United States 53105
    887 HSHS Sacred Heart Hospital Eau Claire Wisconsin United States 54701
    888 Marshfield Clinic Cancer Center at Sacred Heart Eau Claire Wisconsin United States 54701
    889 Saint Agnes Hospital/Agnesian Cancer Center Fond Du Lac Wisconsin United States 54935
    890 Aurora Health Center-Fond du Lac Fond Du Lac Wisconsin United States 54937
    891 Aurora Health Care Germantown Health Center Germantown Wisconsin United States 53022
    892 Aurora Cancer Care-Grafton Grafton Wisconsin United States 53024
    893 Green Bay Oncology at Saint Vincent Hospital Green Bay Wisconsin United States 54301-3526
    894 Bellin Memorial Hospital Green Bay Wisconsin United States 54301
    895 Saint Vincent Hospital Cancer Center Green Bay Green Bay Wisconsin United States 54301
    896 Green Bay Oncology Limited at Saint Mary's Hospital Green Bay Wisconsin United States 54303
    897 Saint Vincent Hospital Cancer Center at Saint Mary's Green Bay Wisconsin United States 54303
    898 Aurora BayCare Medical Center Green Bay Wisconsin United States 54311
    899 UW Cancer Center Johnson Creek Johnson Creek Wisconsin United States 53038
    900 Aurora Cancer Care-Kenosha South Kenosha Wisconsin United States 53142
    901 Gundersen Lutheran Medical Center La Crosse Wisconsin United States 54601
    902 Dean Hematology and Oncology Clinic Madison Wisconsin United States 53717
    903 University of Wisconsin Hospital and Clinics Madison Wisconsin United States 53792
    904 Holy Family Memorial Hospital Manitowoc Wisconsin United States 54221
    905 Aurora Bay Area Medical Group-Marinette Marinette Wisconsin United States 54143
    906 Bay Area Medical Center Marinette Wisconsin United States 54143
    907 Marshfield Medical Center-Marshfield Marshfield Wisconsin United States 54449
    908 Marshfield Medical Center Marshfield Wisconsin United States 54449
    909 Aurora Cancer Care-Milwaukee Milwaukee Wisconsin United States 53209
    910 Ascension Southeast Wisconsin Hospital - Saint Joseph Campus Milwaukee Wisconsin United States 53210
    911 Aurora Saint Luke's Medical Center Milwaukee Wisconsin United States 53215
    912 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    913 Aurora Sinai Medical Center Milwaukee Wisconsin United States 53233
    914 Marshfield Clinic-Minocqua Center Minocqua Wisconsin United States 54548
    915 ProHealth D N Greenwald Center Mukwonago Wisconsin United States 53149
    916 Cancer Center of Western Wisconsin New Richmond Wisconsin United States 54017
    917 ProHealth Oconomowoc Memorial Hospital Oconomowoc Wisconsin United States 53066
    918 Saint Vincent Hospital Cancer Center at Oconto Falls Oconto Falls Wisconsin United States 54154
    919 Vince Lombardi Cancer Clinic - Oshkosh Oshkosh Wisconsin United States 54904
    920 Aurora Cancer Care-Racine Racine Wisconsin United States 53406
    921 Ascension Saint Mary's Hospital Rhinelander Wisconsin United States 54501
    922 Saint Mary's Hospital Rhinelander Wisconsin United States 54501
    923 Marshfield Medical Center-Rice Lake Rice Lake Wisconsin United States 54868
    924 HSHS Saint Nicholas Hospital Sheboygan Wisconsin United States 53081
    925 Vince Lombardi Cancer Clinic-Sheboygan Sheboygan Wisconsin United States 53081
    926 Ascension Saint Michael's Hospital Stevens Point Wisconsin United States 54481
    927 Green Bay Oncology - Sturgeon Bay Sturgeon Bay Wisconsin United States 54235
    928 Aurora Medical Center in Summit Summit Wisconsin United States 53066
    929 Vince Lombardi Cancer Clinic-Two Rivers Two Rivers Wisconsin United States 54241
    930 Aurora Cancer Care-Waukesha Waukesha Wisconsin United States 53188
    931 ProHealth Waukesha Memorial Hospital Waukesha Wisconsin United States 53188
    932 Aspirus Regional Cancer Center Wausau Wisconsin United States 54401
    933 Aurora Cancer Care-Milwaukee West Wauwatosa Wisconsin United States 53226
    934 Aurora West Allis Medical Center West Allis Wisconsin United States 53227
    935 Diagnostic and Treatment Center Weston Wisconsin United States 54476
    936 Marshfield Clinic - Weston Center Weston Wisconsin United States 54476
    937 Aspirus UW Cancer Center Wisconsin Rapids Wisconsin United States 54494
    938 Marshfield Clinic - Wisconsin Rapids Center Wisconsin Rapids Wisconsin United States 54494
    939 Rocky Mountain Oncology Casper Wyoming United States 82609
    940 Welch Cancer Center Sheridan Wyoming United States 82801
    941 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
    942 CancerCare Manitoba Winnipeg Manitoba Canada R3E 0V9
    943 Grand River Regional Cancer Centre at Grand River Hospital Kitchener Ontario Canada N2G 1G3
    944 Ottawa Hospital and Cancer Center-General Campus Ottawa Ontario Canada K1H 8L6
    945 Health Sciences North Sudbury Ontario Canada P3E 5J1
    946 Odette Cancer Centre- Sunnybrook Health Sciences Centre Toronto Ontario Canada M4N 3M5
    947 University Health Network-Princess Margaret Hospital Toronto Ontario Canada M5G 2M9
    948 CHUM - Hopital Notre-Dame Montreal Quebec Canada H2L 4M1
    949 McGill University Department of Oncology Montreal Quebec Canada H2W 1S6
    950 CHUM - Centre Hospitalier de l'Universite de Montreal Montreal Quebec Canada H2X 3E4

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Ahmad Tarhini, ECOG-ACRIN Cancer Research Group

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01274338
    Other Study ID Numbers:
    • NCI-2011-02649
    • NCI-2011-02649
    • E1609
    • P50CA121973
    • U10CA180820
    • U10CA021115
    • U24CA196172
    First Posted:
    Jan 11, 2011
    Last Update Posted:
    May 27, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by National Cancer Institute (NCI)
    Ipilimumab
    Interferon Alfa-2b
    Melanoma
    Additional relevant MeSH terms:
    Melanoma
    Skin Neoplasms
    Interferons
    Interferon-alpha
    Interferon-alfa-1b
    Ipilimumab

    Study Results

    Participant Flow

    Recruitment Details A total of 1673 patients, including 1670 adult patients and 3 pediatric patients, were accrued between May 25, 2011 and July 26, 2016. Accrual of adult patients were completed on August 15, 2014. The study was reactivated to accrue pediatric patients on September 23, 2014.
    Pre-assignment Detail
    Arm/Group Title Arm A (HIP) Arm B (HDI) Arm C (LIP) Arm D (HIP; Pediatric) Arm E (HDI; Pediatric) Arm F (LIP; Pediatric)
    Arm/Group Description Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (ages 12-17) Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. (ages 12-17) Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (ages 12-17)
    Period Title: Overall Study
    STARTED 511 636 523 1 1 1
    Received Treatment 503 520 516 1 1 1
    Data Available for the FACT-G and FACT-BRM Analyses 110 114 97 0 0 0
    Data Available for FACIT-D Analysis 109 114 97 0 0 0
    COMPLETED 108 182 198 0 0 1
    NOT COMPLETED 403 454 325 1 1 0

    Baseline Characteristics

    Arm/Group Title Arm A (HIP) Arm B (HDI) Arm C (LIP) Arm D (HIP; Pediatric) Arm E (HDI; Pediatric) Arm F (LIP; Pediatric) Total
    Arm/Group Description Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (ages 12-17) Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. (ages 12-17) Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (ages 12-17) Total of all reporting groups
    Overall Participants 511 636 523 1 1 1 1673
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    54
    54
    54
    15
    17
    17
    54
    Sex: Female, Male (Count of Participants)
    Female
    169
    33.1%
    241
    37.9%
    195
    37.3%
    1
    100%
    1
    100%
    0
    0%
    607
    36.3%
    Male
    342
    66.9%
    395
    62.1%
    328
    62.7%
    0
    0%
    0
    0%
    1
    100%
    1066
    63.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    8
    1.6%
    20
    3.1%
    16
    3.1%
    0
    0%
    0
    0%
    0
    0%
    44
    2.6%
    Not Hispanic or Latino
    484
    94.7%
    591
    92.9%
    488
    93.3%
    1
    100%
    1
    100%
    1
    100%
    1566
    93.6%
    Unknown or Not Reported
    19
    3.7%
    25
    3.9%
    19
    3.6%
    0
    0%
    0
    0%
    0
    0%
    63
    3.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    6
    1.2%
    2
    0.3%
    3
    0.6%
    0
    0%
    0
    0%
    0
    0%
    11
    0.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    0.2%
    4
    0.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    0.3%
    White
    497
    97.3%
    620
    97.5%
    510
    97.5%
    1
    100%
    1
    100%
    1
    100%
    1630
    97.4%
    More than one race
    0
    0%
    1
    0.2%
    2
    0.4%
    0
    0%
    0
    0%
    0
    0%
    3
    0.2%
    Unknown or Not Reported
    7
    1.4%
    9
    1.4%
    8
    1.5%
    0
    0%
    0
    0%
    0
    0%
    24
    1.4%

    Outcome Measures

    1. Primary Outcome
    Title Recurrence-free Survival (RFS; Arm B [HDI] vs. Arm C [LIP])
    Description Recurrence-free survival is defined as the time from randomization to recurrence or death, whichever occurs first. The following criteria constitute the only acceptable evidence of disease recurrence. Lung and liver: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease. Central Nervous System: A positive brain CT or MRI scan or CSF cytology. Cutaneous, Subcutaneous and Lymph Node Recurrence: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease. Bone and Other Organs: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease identified on two different radiologic studies: i.e., positive nuclear bone scan or PET scan and contrast GI series or ultrasound, X-ray or CT of abdomen for abdominal disease.
    Time Frame Assessed every 3 months for 2 years, then every 6 months for years 3-5 and then annually up to 8 years

    Outcome Measure Data

    Analysis Population Description
    Concurrently randomized patients on Arms B and C
    Arm/Group Title Arm B (HDI) Arm C (LIP)
    Arm/Group Description Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants 528 523
    Median (95% Confidence Interval) [years]
    2.5
    4.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm B (HDI), Arm C (LIP)
    Comments This study has a two-step hierarchical approach. In the first step, the low-dose Ipi (LIP) will be compared with HDI. If the low-dose Ipi is significantly better than HDI, then the high-dose Ipi will be compared with HDI as a second step. When comparing the two investigational treatment groups, the primary comparison will be an intent to treat analysis of recurrence free survival (RFS; First Co-primary Endpoint) and overall survival (OS; Second Co-primary Endpoint).
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.065
    Comments This design provides at least 80% power at a one sided type I error rate of 0.003.
    Method Log Rank
    Comments Stratified logrank test
    2. Primary Outcome
    Title 5-year Overall Survival (OS) Rate (Arm B [HDI] vs. Arm C [LIP])
    Description Overall survival is defined as the time from randomization to death or date last known alive.
    Time Frame Assessed every 3 months for 2 years, then every 6 months for years 3-5

    Outcome Measure Data

    Analysis Population Description
    Concurrently randomized patients on Arms B and C
    Arm/Group Title Arm B (HDI) Arm C (LIP)
    Arm/Group Description Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants 528 523
    Number (95% Confidence Interval) [proportion of participants]
    0.67
    0.1%
    0.72
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm B (HDI), Arm C (LIP)
    Comments This study has a two-step hierarchical approach. In the first step, the low-dose Ipi (LIP) will be compared with HDI. If the low-dose Ipi is significantly better than HDI, then the high-dose Ipi will be compared with HDI as a second step. When comparing the two investigational treatment groups, the primary comparison will be an intent to treat analysis of recurrence free survival (RFS; First Co-primary Endpoint) and overall survival (OS; Second Co-primary Endpoint).
    Type of Statistical Test Superiority
    Comments This design will provide 80% power to detect the difference between the two arms at a one-sided type I error rate of 0.022.
    Statistical Test of Hypothesis p-Value 0.044
    Comments
    Method Log Rank
    Comments Stratified logrank test
    3. Primary Outcome
    Title Recurrence-free Survival (RFS; Arm A [HIP] vs. Arm B [HDI])
    Description Recurrence-free survival is defined as the time from randomization to recurrence or death, whichever occurs first. The following criteria constitute the only acceptable evidence of disease recurrence. Lung and liver: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease. Central Nervous System: A positive brain CT or MRI scan or CSF cytology. Cutaneous, Subcutaneous and Lymph Node Recurrence: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease. Bone and Other Organs: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease identified on two different radiologic studies: i.e., positive nuclear bone scan or PET scan and contrast GI series or ultrasound, X-ray or CT of abdomen for abdominal disease.
    Time Frame Assessed every 3 months for 2 years, then every 6 months for years 3-5 and then annually up to 8 years

    Outcome Measure Data

    Analysis Population Description
    Concurrently randomized patients on Arms A and B
    Arm/Group Title Arm A (HIP) Arm B (HDI)
    Arm/Group Description Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.
    Measure Participants 511 478
    Median (95% Confidence Interval) [years]
    3.9
    2.4
    4. Primary Outcome
    Title 5-year Overall Survival (OS) Rate (Arm A [HIP] vs. Arm B [HDI])
    Description Overall survival is defined as the time from randomization to death or date last known alive.
    Time Frame Assessed every 3 months for 2 years, then every 6 months for years 3-5

    Outcome Measure Data

    Analysis Population Description
    Concurrently randomized patients on Arms A and B
    Arm/Group Title Arm A (HIP) Arm B (HDI)
    Arm/Group Description Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.
    Measure Participants 511 478
    Number (95% Confidence Interval) [proportion of participants]
    0.70
    0.1%
    0.65
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm B (HDI), Arm C (LIP)
    Comments This study has a two-step hierarchical approach. In the first step, the low-dose Ipi (LIP) will be compared with HDI. If the low-dose Ipi is significantly better than HDI, then the high-dose Ipi will be compared with HDI as a second step. When comparing the two investigational treatment groups, the primary comparison will be an intent to treat analysis of recurrence free survival (RFS; First Co-primary Endpoint) and overall survival (OS; Second Co-primary Endpoint).
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.289
    Comments If low dose Ipi (LIP) vs. HDI is significant for OS at the 2.2% level, then we will compare high dose Ipi (HIP) vs. HDI at the 2.2% level.
    Method Log Rank
    Comments Stratified logrank test
    5. Secondary Outcome
    Title Change in FACT-G (Functional Assessment of Cancer Therapy - General) Total Score From Baseline to 3 Months
    Description The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-G total score ranges between 0 and 108. The higher the score, the better the quality of life. Change in FACT-G total score from baseline to 3 months was calculated as month 3 score - baseline score.
    Time Frame Assessed at baseline and 3 months

    Outcome Measure Data

    Analysis Population Description
    Patients with baseline and 3-month FACT-G assessments were included in this analysis. Pediatric patients did not participate in the quality of life part of the study.
    Arm/Group Title Arm A (HIP) Arm B (HDI) Arm C (LIP)
    Arm/Group Description Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants 110 114 97
    Mean (Standard Deviation) [score on a scale]
    -4.9
    (14.1)
    -12.9
    (14.1)
    -3.4
    (13.2)
    6. Secondary Outcome
    Title Change in FACIT-D (Functional Assessment of Cancer Therapy - Diarrhea) Diarrhea Subscale Score From Baseline to 3 Months
    Description The diarrhea subscale of The Functional Assessment of Chronic Illness Therapy - Diarrhea (FACIT-D) is an 11-item questionnaire with a scale of 0-4. The FACIT-D diarrhea subscale score ranges between 0 and 44. The higher the score, the better the quality of life. Change in FACIT-D diarrhea subscale score from baseline to 3 months was calculated as month 3 score - baseline score.
    Time Frame Assessed at baseline and 3 months

    Outcome Measure Data

    Analysis Population Description
    Patients with baseline and 3-month FACIT-D diarrhea subscale assessments were included in this analysis. Pediatric patients did not participate in the quality of life part of the study.
    Arm/Group Title Arm A (HIP) Arm B (HDI) Arm C (LIP)
    Arm/Group Description Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants 109 114 97
    Mean (Standard Deviation) [score on a scale]
    -3.7
    (6.9)
    -0.7
    (2.7)
    -2.2
    (5.1)
    7. Secondary Outcome
    Title Change in FACT-BRM (Functional Assessment of Cancer Therapy - Biologic Response Modifiers) Total Score From Baseline to 3 Months
    Description The Functional Assessment of Cancer Therapy - Biologic Response Modifiers (FACT-BRM) is a questionnaire including FACT-G (The Functional Assessment of Cancer Therapy - General) and additional sections addressing physical and mental quality of life aspects. It is a 40-item questionnaire with a scale of 0-4. The FACT-BRM total score ranges between 0 and 160. The higher the score, the better the quality of life. Change in FACT-BRM total score from baseline to 3 months is calculated as month 3 score - baseline score.
    Time Frame Assessed at baseline and 3 months

    Outcome Measure Data

    Analysis Population Description
    Patients with baseline and 3-month FACT-BRM assessments were included in this analysis. Pediatric patients did not participate in the quality of life part of the study.
    Arm/Group Title Arm A (HIP) Arm B (HDI) Arm C (LIP)
    Arm/Group Description Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants 110 114 97
    Mean (Standard Deviation) [score on a scale]
    -8.3
    (19.7)
    -22.7
    (20.4)
    -6.2
    (18.9)

    Adverse Events

    Time Frame Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years
    Adverse Event Reporting Description Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
    Arm/Group Title Arm A (HIP) Arm B (HDI) Arm C (LIP) Arm D (HIP; Pediatric) Arm E (HDI; Pediatric) Arm F (LIP; Pediatric)
    Arm/Group Description Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
    All Cause Mortality
    Arm A (HIP) Arm B (HDI) Arm C (LIP) Arm D (HIP; Pediatric) Arm E (HDI; Pediatric) Arm F (LIP; Pediatric)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 153/511 (29.9%) 168/636 (26.4%) 135/523 (25.8%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Serious Adverse Events
    Arm A (HIP) Arm B (HDI) Arm C (LIP) Arm D (HIP; Pediatric) Arm E (HDI; Pediatric) Arm F (LIP; Pediatric)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 292/503 (58.1%) 410/520 (78.8%) 197/516 (38.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Blood and lymphatic system disorders
    Anemia 3/503 (0.6%) 4/520 (0.8%) 5/516 (1%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Febrile neutropenia 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Leukocytosis 1/503 (0.2%) 1/520 (0.2%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Blood and lymphatic disorders - Other 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Cardiac disorders
    Acute coronary syndrome 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Atrial fibrillation 2/503 (0.4%) 1/520 (0.2%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Cardiac arrest 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Chest pain - cardiac 1/503 (0.2%) 1/520 (0.2%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Heart failure 0/503 (0%) 2/520 (0.4%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Left ventricular systolic dysfunction 2/503 (0.4%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Myocardial infarction 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Myocarditis 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Restrictive cardiomyopathy 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Sinus tachycardia 3/503 (0.6%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Supraventricular tachycardia 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Ventricular arrhythmia 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Ear and labyrinth disorders
    Hearing impaired 2/503 (0.4%) 1/520 (0.2%) 2/516 (0.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Vertigo 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Vestibular disorder 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Endocrine disorders
    Adrenal insufficiency 18/503 (3.6%) 0/520 (0%) 12/516 (2.3%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hyperthyroidism 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hypothyroidism 5/503 (1%) 1/520 (0.2%) 3/516 (0.6%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Endocrine disorders - Other, specify 43/503 (8.5%) 0/520 (0%) 20/516 (3.9%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Eye disorders
    Cataract 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Conjunctivitis 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Uveitis 1/503 (0.2%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Eye disorders - Other, specify 2/503 (0.4%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Gastrointestinal disorders
    Abdominal distension 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Abdominal pain 4/503 (0.8%) 2/520 (0.4%) 4/516 (0.8%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Anal fistula 0/503 (0%) 0/520 (0%) 2/516 (0.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Colitis 52/503 (10.3%) 1/520 (0.2%) 35/516 (6.8%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Colonic perforation 6/503 (1.2%) 0/520 (0%) 5/516 (1%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Colonic ulcer 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Constipation 2/503 (0.4%) 2/520 (0.4%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Diarrhea 73/503 (14.5%) 4/520 (0.8%) 54/516 (10.5%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Dysphagia 2/503 (0.4%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Enterocolitis 3/503 (0.6%) 0/520 (0%) 6/516 (1.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Esophagitis 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Gastric perforation 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Gastric ulcer 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Gastritis 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Gastrointestinal pain 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Ileal perforation 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Ileus 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Intra-abdominal hemorrhage 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Lower gastrointestinal hemorrhage 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Mucositis oral 3/503 (0.6%) 1/520 (0.2%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Nausea 19/503 (3.8%) 25/520 (4.8%) 5/516 (1%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Oral pain 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Pancreatitis 5/503 (1%) 2/520 (0.4%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Peritoneal necrosis 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Proctitis 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Rectal fistula 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Rectal hemorrhage 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Rectal pain 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Small intestinal obstruction 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Vomiting 13/503 (2.6%) 12/520 (2.3%) 3/516 (0.6%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Gastrointestinal disorders - Other 3/503 (0.6%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    General disorders
    Chills 1/503 (0.2%) 2/520 (0.4%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Death NOS 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Fatigue 26/503 (5.2%) 120/520 (23.1%) 14/516 (2.7%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Fever 6/503 (1.2%) 4/520 (0.8%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Flu like symptoms 1/503 (0.2%) 14/520 (2.7%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Injection site reaction 0/503 (0%) 2/520 (0.4%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Non-cardiac chest pain 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Pain 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hepatobiliary disorders
    Hepatobiliary disorders - Other, specify 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Immune system disorders
    Autoimmune disorder 16/503 (3.2%) 2/520 (0.4%) 5/516 (1%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Immune system disorders - Other, specify 5/503 (1%) 0/520 (0%) 2/516 (0.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Infections and infestations
    Abdominal infection 1/503 (0.2%) 0/520 (0%) 2/516 (0.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Enterocolitis infectious 3/503 (0.6%) 0/520 (0%) 2/516 (0.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Lung infection 5/503 (1%) 2/520 (0.4%) 2/516 (0.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Meningitis 4/503 (0.8%) 0/520 (0%) 2/516 (0.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Peritoneal infection 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Sepsis 2/503 (0.4%) 1/520 (0.2%) 2/516 (0.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Skin infection 3/503 (0.6%) 1/520 (0.2%) 3/516 (0.6%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Soft tissue infection 1/503 (0.2%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Urinary tract infection 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Infections and infestations - Other 3/503 (0.6%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Investigations
    Alanine aminotransferase increased 40/503 (8%) 78/520 (15%) 15/516 (2.9%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Alkaline phosphatase increased 4/503 (0.8%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Aspartate aminotransferase increased 32/503 (6.4%) 61/520 (11.7%) 11/516 (2.1%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Blood bilirubin increased 6/503 (1.2%) 2/520 (0.4%) 2/516 (0.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Cholesterol high 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    CPK increased 1/503 (0.2%) 31/520 (6%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Creatinine increased 1/503 (0.2%) 0/520 (0%) 3/516 (0.6%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Ejection fraction decreased 1/503 (0.2%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Lipase increased 23/503 (4.6%) 4/520 (0.8%) 18/516 (3.5%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Lymphocyte count decreased 4/503 (0.8%) 65/520 (12.5%) 7/516 (1.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Neutrophil count decreased 4/503 (0.8%) 206/520 (39.6%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Platelet count decreased 0/503 (0%) 4/520 (0.8%) 2/516 (0.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Serum amylase increased 2/503 (0.4%) 0/520 (0%) 5/516 (1%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Weight loss 1/503 (0.2%) 6/520 (1.2%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    White blood cell decreased 1/503 (0.2%) 70/520 (13.5%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Investigations - Other, specify 3/503 (0.6%) 0/520 (0%) 3/516 (0.6%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Metabolism and nutrition disorders
    Alkalosis 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Anorexia 2/503 (0.4%) 13/520 (2.5%) 3/516 (0.6%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Dehydration 19/503 (3.8%) 8/520 (1.5%) 7/516 (1.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hypercalcemia 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hyperglycemia 5/503 (1%) 1/520 (0.2%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hypertriglyceridemia 0/503 (0%) 10/520 (1.9%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hyperuricemia 1/503 (0.2%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hypoalbuminemia 2/503 (0.4%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hypocalcemia 2/503 (0.4%) 2/520 (0.4%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hypokalemia 9/503 (1.8%) 6/520 (1.2%) 4/516 (0.8%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hyponatremia 17/503 (3.4%) 6/520 (1.2%) 10/516 (1.9%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hypophosphatemia 7/503 (1.4%) 29/520 (5.6%) 7/516 (1.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Metabolism and nutrition - Other 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 4/503 (0.8%) 4/520 (0.8%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Arthritis 2/503 (0.4%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Back pain 0/503 (0%) 1/520 (0.2%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Bone pain 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Flank pain 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Generalized muscle weakness 5/503 (1%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Muscle weakness left-sided 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Muscle weakness lower limb 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Muscle weakness right-sided 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Myalgia 6/503 (1.2%) 11/520 (2.1%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Neck pain 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Osteonecrosis of jaw 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Pain in extremity 1/503 (0.2%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Musculoskeletal and connective - Other 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Treatment related secondary malignancy 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Nervous system disorders
    Cognitive disturbance 2/503 (0.4%) 2/520 (0.4%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Dizziness 0/503 (0%) 4/520 (0.8%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Encephalopathy 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Facial nerve disorder 1/503 (0.2%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Headache 16/503 (3.2%) 15/520 (2.9%) 12/516 (2.3%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Intracranial hemorrhage 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Peripheral motor neuropathy 3/503 (0.6%) 3/520 (0.6%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Peripheral sensory neuropathy 1/503 (0.2%) 0/520 (0%) 4/516 (0.8%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Syncope 6/503 (1.2%) 9/520 (1.7%) 3/516 (0.6%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Nervous system disorders - Other 3/503 (0.6%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Psychiatric disorders
    Anxiety 0/503 (0%) 7/520 (1.3%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Confusion 2/503 (0.4%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Delirium 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Depression 0/503 (0%) 17/520 (3.3%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Insomnia 0/503 (0%) 4/520 (0.8%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Mania 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Psychosis 0/503 (0%) 2/520 (0.4%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Suicide attempt 0/503 (0%) 2/520 (0.4%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Psychiatric disorders - Other, specify 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Renal and urinary disorders
    Acute kidney injury 3/503 (0.6%) 1/520 (0.2%) 3/516 (0.6%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Chronic kidney disease 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Renal calculi 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Renal and urinary disorders - Other 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome 0/503 (0%) 1/520 (0.2%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Dyspnea 3/503 (0.6%) 3/520 (0.6%) 2/516 (0.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hypoxia 2/503 (0.4%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Pleural effusion 1/503 (0.2%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Pneumonitis 7/503 (1.4%) 0/520 (0%) 2/516 (0.4%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Pulmonary edema 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Respiratory failure 2/503 (0.4%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Respiratory thoracic mediastinal - Other 0/503 (0%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Skin and subcutaneous tissue disorders
    Dry skin 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Pruritus 11/503 (2.2%) 0/520 (0%) 11/516 (2.1%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Rash acneiform 2/503 (0.4%) 0/520 (0%) 1/516 (0.2%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Rash maculo-papular 40/503 (8%) 5/520 (1%) 23/516 (4.5%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Skin ulceration 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Vascular disorders
    Hypertension 3/503 (0.6%) 9/520 (1.7%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Hypotension 5/503 (1%) 6/520 (1.2%) 4/516 (0.8%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Thromboembolic event 3/503 (0.6%) 0/520 (0%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Vascular disorders - Other, specify 0/503 (0%) 1/520 (0.2%) 0/516 (0%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Other (Not Including Serious) Adverse Events
    Arm A (HIP) Arm B (HDI) Arm C (LIP) Arm D (HIP; Pediatric) Arm E (HDI; Pediatric) Arm F (LIP; Pediatric)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 495/503 (98.4%) 510/520 (98.1%) 488/516 (94.6%) 0/1 (0%) 0/1 (0%) 0/1 (0%)
    Blood and lymphatic system disorders
    Anemia 90/503 (17.9%) 209/520 (40.2%) 69/516 (13.4%) 69/1 (6900%) 69/1 (6900%) 69/1 (6900%)
    Endocrine disorders
    Adrenal insufficiency 61/503 (12.1%) 3/520 (0.6%) 42/516 (8.1%) 42/1 (4200%) 42/1 (4200%) 42/1 (4200%)
    Hyperthyroidism 31/503 (6.2%) 17/520 (3.3%) 21/516 (4.1%) 21/1 (2100%) 21/1 (2100%) 21/1 (2100%)
    Hypothyroidism 103/503 (20.5%) 50/520 (9.6%) 54/516 (10.5%) 54/1 (5400%) 54/1 (5400%) 54/1 (5400%)
    Endocrine disorders - Other, specify 94/503 (18.7%) 12/520 (2.3%) 65/516 (12.6%) 65/1 (6500%) 65/1 (6500%) 65/1 (6500%)
    Eye disorders
    Blurred vision 37/503 (7.4%) 29/520 (5.6%) 15/516 (2.9%) 15/1 (1500%) 15/1 (1500%) 15/1 (1500%)
    Gastrointestinal disorders
    Abdominal pain 103/503 (20.5%) 39/520 (7.5%) 89/516 (17.2%) 89/1 (8900%) 89/1 (8900%) 89/1 (8900%)
    Colitis 29/503 (5.8%) 0/520 (0%) 17/516 (3.3%) 17/1 (1700%) 17/1 (1700%) 17/1 (1700%)
    Constipation 44/503 (8.7%) 110/520 (21.2%) 36/516 (7%) 36/1 (3600%) 36/1 (3600%) 36/1 (3600%)
    Diarrhea 234/503 (46.5%) 176/520 (33.8%) 231/516 (44.8%) 231/1 (23100%) 231/1 (23100%) 231/1 (23100%)
    Dry mouth 20/503 (4%) 88/520 (16.9%) 14/516 (2.7%) 14/1 (1400%) 14/1 (1400%) 14/1 (1400%)
    Mucositis oral 16/503 (3.2%) 35/520 (6.7%) 7/516 (1.4%) 7/1 (700%) 7/1 (700%) 7/1 (700%)
    Nausea 182/503 (36.2%) 361/520 (69.4%) 147/516 (28.5%) 147/1 (14700%) 147/1 (14700%) 147/1 (14700%)
    Vomiting 83/503 (16.5%) 133/520 (25.6%) 54/516 (10.5%) 54/1 (5400%) 54/1 (5400%) 54/1 (5400%)
    General disorders
    Chills 61/503 (12.1%) 178/520 (34.2%) 34/516 (6.6%) 34/1 (3400%) 34/1 (3400%) 34/1 (3400%)
    Fatigue 328/503 (65.2%) 456/520 (87.7%) 298/516 (57.8%) 298/1 (29800%) 298/1 (29800%) 298/1 (29800%)
    Fever 98/503 (19.5%) 174/520 (33.5%) 53/516 (10.3%) 53/1 (5300%) 53/1 (5300%) 53/1 (5300%)
    Flu like symptoms 39/503 (7.8%) 254/520 (48.8%) 34/516 (6.6%) 34/1 (3400%) 34/1 (3400%) 34/1 (3400%)
    Malaise 10/503 (2%) 31/520 (6%) 6/516 (1.2%) 6/1 (600%) 6/1 (600%) 6/1 (600%)
    Pain 6/503 (1.2%) 31/520 (6%) 11/516 (2.1%) 11/1 (1100%) 11/1 (1100%) 11/1 (1100%)
    Investigations
    Alanine aminotransferase increased 140/503 (27.8%) 342/520 (65.8%) 86/516 (16.7%) 86/1 (8600%) 86/1 (8600%) 86/1 (8600%)
    Alkaline phosphatase increased 53/503 (10.5%) 42/520 (8.1%) 26/516 (5%) 26/1 (2600%) 26/1 (2600%) 26/1 (2600%)
    Aspartate aminotransferase increased 125/503 (24.9%) 367/520 (70.6%) 72/516 (14%) 72/1 (7200%) 72/1 (7200%) 72/1 (7200%)
    Blood bilirubin increased 24/503 (4.8%) 48/520 (9.2%) 22/516 (4.3%) 22/1 (2200%) 22/1 (2200%) 22/1 (2200%)
    CPK increased 3/503 (0.6%) 176/520 (33.8%) 3/516 (0.6%) 3/1 (300%) 3/1 (300%) 3/1 (300%)
    Lipase increased 48/503 (9.5%) 9/520 (1.7%) 44/516 (8.5%) 44/1 (4400%) 44/1 (4400%) 44/1 (4400%)
    Lymphocyte count decreased 32/503 (6.4%) 169/520 (32.5%) 53/516 (10.3%) 53/1 (5300%) 53/1 (5300%) 53/1 (5300%)
    Neutrophil count decreased 13/503 (2.6%) 317/520 (61%) 19/516 (3.7%) 19/1 (1900%) 19/1 (1900%) 19/1 (1900%)
    Platelet count decreased 32/503 (6.4%) 278/520 (53.5%) 25/516 (4.8%) 25/1 (2500%) 25/1 (2500%) 25/1 (2500%)
    Serum amylase increased 26/503 (5.2%) 9/520 (1.7%) 22/516 (4.3%) 22/1 (2200%) 22/1 (2200%) 22/1 (2200%)
    Weight loss 57/503 (11.3%) 214/520 (41.2%) 35/516 (6.8%) 35/1 (3500%) 35/1 (3500%) 35/1 (3500%)
    White blood cell decreased 12/503 (2.4%) 273/520 (52.5%) 15/516 (2.9%) 15/1 (1500%) 15/1 (1500%) 15/1 (1500%)
    Investigations - Other, specify 107/503 (21.3%) 95/520 (18.3%) 91/516 (17.6%) 91/1 (9100%) 91/1 (9100%) 91/1 (9100%)
    Metabolism and nutrition disorders
    Anorexia 102/503 (20.3%) 288/520 (55.4%) 73/516 (14.1%) 73/1 (7300%) 73/1 (7300%) 73/1 (7300%)
    Dehydration 20/503 (4%) 34/520 (6.5%) 11/516 (2.1%) 11/1 (1100%) 11/1 (1100%) 11/1 (1100%)
    Hyperglycemia 27/503 (5.4%) 39/520 (7.5%) 18/516 (3.5%) 18/1 (1800%) 18/1 (1800%) 18/1 (1800%)
    Hypoalbuminemia 31/503 (6.2%) 51/520 (9.8%) 31/516 (6%) 31/1 (3100%) 31/1 (3100%) 31/1 (3100%)
    Hypocalcemia 25/503 (5%) 90/520 (17.3%) 17/516 (3.3%) 17/1 (1700%) 17/1 (1700%) 17/1 (1700%)
    Hypokalemia 32/503 (6.4%) 52/520 (10%) 21/516 (4.1%) 21/1 (2100%) 21/1 (2100%) 21/1 (2100%)
    Hyponatremia 36/503 (7.2%) 24/520 (4.6%) 24/516 (4.7%) 24/1 (2400%) 24/1 (2400%) 24/1 (2400%)
    Hypophosphatemia 17/503 (3.4%) 93/520 (17.9%) 18/516 (3.5%) 18/1 (1800%) 18/1 (1800%) 18/1 (1800%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 58/503 (11.5%) 102/520 (19.6%) 44/516 (8.5%) 44/1 (4400%) 44/1 (4400%) 44/1 (4400%)
    Back pain 7/503 (1.4%) 27/520 (5.2%) 8/516 (1.6%) 8/1 (800%) 8/1 (800%) 8/1 (800%)
    Generalized muscle weakness 20/503 (4%) 31/520 (6%) 8/516 (1.6%) 8/1 (800%) 8/1 (800%) 8/1 (800%)
    Myalgia 34/503 (6.8%) 154/520 (29.6%) 23/516 (4.5%) 23/1 (2300%) 23/1 (2300%) 23/1 (2300%)
    Nervous system disorders
    Dizziness 45/503 (8.9%) 109/520 (21%) 25/516 (4.8%) 25/1 (2500%) 25/1 (2500%) 25/1 (2500%)
    Dysgeusia 21/503 (4.2%) 165/520 (31.7%) 16/516 (3.1%) 16/1 (1600%) 16/1 (1600%) 16/1 (1600%)
    Headache 152/503 (30.2%) 238/520 (45.8%) 122/516 (23.6%) 122/1 (12200%) 122/1 (12200%) 122/1 (12200%)
    Peripheral sensory neuropathy 27/503 (5.4%) 43/520 (8.3%) 25/516 (4.8%) 25/1 (2500%) 25/1 (2500%) 25/1 (2500%)
    Psychiatric disorders
    Anxiety 15/503 (3%) 93/520 (17.9%) 14/516 (2.7%) 14/1 (1400%) 14/1 (1400%) 14/1 (1400%)
    Depression 20/503 (4%) 160/520 (30.8%) 17/516 (3.3%) 17/1 (1700%) 17/1 (1700%) 17/1 (1700%)
    Insomnia 28/503 (5.6%) 92/520 (17.7%) 25/516 (4.8%) 25/1 (2500%) 25/1 (2500%) 25/1 (2500%)
    Respiratory, thoracic and mediastinal disorders
    Cough 26/503 (5.2%) 42/520 (8.1%) 17/516 (3.3%) 17/1 (1700%) 17/1 (1700%) 17/1 (1700%)
    Dyspnea 28/503 (5.6%) 69/520 (13.3%) 18/516 (3.5%) 18/1 (1800%) 18/1 (1800%) 18/1 (1800%)
    Skin and subcutaneous tissue disorders
    Alopecia 11/503 (2.2%) 115/520 (22.1%) 8/516 (1.6%) 8/1 (800%) 8/1 (800%) 8/1 (800%)
    Dry skin 23/503 (4.6%) 51/520 (9.8%) 17/516 (3.3%) 17/1 (1700%) 17/1 (1700%) 17/1 (1700%)
    Pruritus 226/503 (44.9%) 84/520 (16.2%) 215/516 (41.7%) 215/1 (21500%) 215/1 (21500%) 215/1 (21500%)
    Rash maculo-papular 281/503 (55.9%) 98/520 (18.8%) 229/516 (44.4%) 229/1 (22900%) 229/1 (22900%) 229/1 (22900%)
    Skin and subcutaneous tissue - Other 27/503 (5.4%) 35/520 (6.7%) 19/516 (3.7%) 19/1 (1900%) 19/1 (1900%) 19/1 (1900%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Study Statistician
    Organization ECOG-ACRIN Biostatistics Center
    Phone 617-632-3012
    Email eatrials@jimmy.harvard.edu
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01274338
    Other Study ID Numbers:
    • NCI-2011-02649
    • NCI-2011-02649
    • E1609
    • P50CA121973
    • U10CA180820
    • U10CA021115
    • U24CA196172
    First Posted:
    Jan 11, 2011
    Last Update Posted:
    May 27, 2021
    Last Verified:
    May 1, 2021