Testing the Addition of the Immunotherapy Drug, Pembrolizumab, to the Usual Radiation Treatment for Newly Diagnosed Early Stage High Intermediate Risk Endometrial Cancer

Phase 3

Active, not recruiting

• Conditions: Stage I Uterine Corpus Cancer AJCC v8; Stage II Uterine Corpus Cancer AJCC v8; Endometrial Endometrioid Adenocarcinoma
• Interventions: Procedure: Biospecimen Collection; Radiation: Brachytherapy; Procedure: Computed Tomography; Radiation: External Beam Radiation Therapy; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: X-Ray Imaging

• Registration Number: NCT04214067
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This phase III trial compares whether the addition of pembrolizumab to radiation therapy is more effective than radiation therapy alone in reducing the risk of cancer coming back (recurrence) in patients with newly diagnosed stage I-II endometrial cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The addition of pembrolizumab to radiation treatment may be more effective than radiation treatment alone in reducing cancer recurrence.

Detailed Description

PRIMARY OBJECTIVE:

I. To compare the 3-year recurrence-free survival of women with high intermediate risk (HIR) stage I/II mismatch repair deficient (dMMR) endometrioid endometrial cancer treated with radiation and pembrolizumab (MK-3475) versus radiation alone.

SECONDARY OBJECTIVES:

I. To describe the safety and tolerability of concurrent pembrolizumab (MK-3475) and radiation compared to radiation alone in patients with MMR deficient high intermediate risk endometrial cancer (HIR EC).

II. To describe the recurrence patterns in each group. III. To measure recurrence free survival at 5 years in each group. IV. To estimate disease specific overall survival in each group. V. To determine whether the addition of pembrolizumab (MK-3475) to radiation, compared with radiation alone is associated with decreased quality of life at 6- and 24-weeks, as measured with the Functional Assessment of Cancer Therapy (FACT)-Endometrial (En) Trial Outcome Index (TOI), increased gastrointestinal (GI) symptoms as measured with the GI subscale, and increased fatigue as measured with the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue scale (short form).

VI. To validate the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM) subscale, which assesses in cancer patients on immunotherapy.

VII. To evaluate the ability of ctDNA to predict outcomes in the experimental and control groups.

CORRELATIVE/TERTIARY OBJECTIVES:

I. To explore the baseline tumor genetic and microenvironment parameters predictive of clinical benefit or resistance to immunotherapy.

II. To determine whether the addition of pembrolizumab (MK-3475) to radiation, compared with radiation alone, is associated with decreased quality of life as measured with the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM subscale) and more self-reported bother from side effects as measured with a single item GP5 "I am bothered by side effects," a question from the FACT-En TOI.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo pelvic external beam radiation therapy (EBRT) daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity.

Patients in both arms also undergo collection of blood samples and computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, or x-ray imaging throughout the trial.

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

Study Timeline

• Study First Submitted: 2019-12-27
• Study First Submitted QC: 2019-12-27
• Study First Posted: 2019-12-30
• Study Start: 2020-04-09
• Status Verified: 2024-10
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-04
• Primary Completion: 2025-02-01
• Study Completion: 2025-02-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 168

Inclusion Criteria

• Patients must have:

  • Stage I endometrioid endometrial cancer and a combination of age and risk factors as listed below:

    • Age >= 70 and 1 or more risk factors

    • Age 50 - < 70 and 2 or more risk factors

    • Age < 50 and 3 risk factors

      • Risk factors:

        • Myometrial invasion >= 50%
        • Lymphovascular space invasion
        • Grade 2 or 3 OR

  • Stage II endometrioid endometrial cancer

    • Note: Patients with isolated tumor cells in sentinel lymph nodes are eligible (considered N0i) as long as there is no evidence of micro- or macro-metastases in any lymph nodes

• CT or MRI abdomen or pelvis and either chest X-ray or CT chest demonstrating no evidence of disease outside of the uterus. Imaging can be performed pre-operatively or post-operatively. CT with contrast is the preferred modality. Positron emission tomography (PET)/CT is NOT to be used for any disease assessment or reassessment unless there is documentation that PET/CT is of diagnostic quality equal to CT with contrast

• Patients must have deficient mismatch repair as demonstrated by lack of expression of at least one mismatch repair protein by immunohistochemistry (IHC) and/or evidence of microsatellite instability (MSI) high. The institutional pathology report documenting MMR deficiency must be submitted

• Patients must have undergone surgical staging with at least hysterectomy, removal of cervix, bilateral (if both are present) salpingo-oophorectomy, and either sentinel lymph node assessment or complete pelvic +/- aortic lymphadenectomy. Secondary staging is allowed to determine stage. Patients with isolated tumor cells in sentinel lymph nodes are eligible (considered N0i) as long as there is no evidence of micro- or macro-metastases in any lymph nodes

• Patients must have received no prior therapy for endometrial cancer, including hormonal therapy, chemotherapy, targeted therapy, immunotherapy or radiation therapy

• Age >= 18

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

• Platelets >= 100,000/mcl (within 14 days prior to registration)

• Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)

• Creatinine =< 1.5 x laboratory upper limit of normal (ULN) (within 14 days prior to registration)

• Bilirubin =< 1.5 x ULN (within 14 days prior to registration) (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (within 14 days prior to registration)

• Thyroid stimulating hormone (TSH) within normal limits (TSH < ULN allowed in euthyroid patients on thyroid replacement therapy)

• Patients must be registered between 1 and 8 weeks after initial (staging) surgery performed for the combined purpose of diagnosis and staging

• Human immunodeficiency virus (HIV) testing is not required by protocol unless clinically indicated. Known HIV positive patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

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Exclusion Criteria

• Patients who are currently participating and receiving cancer-directed study therapy for endometrial cancer or have participated in a study of an investigational agent and received cancer-directed study therapy for endometrial cancer within 4 weeks prior to registration

• Patients who have received prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapeutic antibody or other similar agents

• Patients who have a history of a severe hypersensitivity reaction to monoclonal antibody or MK-3475 (pembrolizumab) and/or its excipients

• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. This includes, but is not limited to, patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible

• Patients with a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis

• Patients who have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to registration:

  • Patients who have received steroids as CT scan contrast premedication may be enrolled
  • The use of inhaled or topical corticosteroids is allowed
  • The use of mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
  • The use of physiologic doses of corticosteroids may be approved after consultation with the study chair (e.g. 10 mg of prednisone used for replacement therapy for adrenal insufficiency)

• Patients who are lactating

• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; and cirrhosis. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection (except for uncomplicated urinary tract infection), interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients who have received any of the prohibited medications

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (EBRT, brachytherapy, pembrolizumab)	Magnetic Resonance Imaging	Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm II (EBRT, brachytherapy, pembrolizumab)	Pembrolizumab	Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm II (EBRT, brachytherapy, pembrolizumab)	Quality-of-Life Assessment	Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm II (EBRT, brachytherapy, pembrolizumab)	Questionnaire Administration	Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm II (EBRT, brachytherapy, pembrolizumab)	X-Ray Imaging	Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm I (EBRT, brachytherapy)	Biospecimen Collection	Patients undergo pelvic EBRT daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm I (EBRT, brachytherapy)	Brachytherapy	Patients undergo pelvic EBRT daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm I (EBRT, brachytherapy)	Computed Tomography	Patients undergo pelvic EBRT daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm I (EBRT, brachytherapy)	External Beam Radiation Therapy	Patients undergo pelvic EBRT daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm I (EBRT, brachytherapy)	Magnetic Resonance Imaging	Patients undergo pelvic EBRT daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm I (EBRT, brachytherapy)	Quality-of-Life Assessment	Patients undergo pelvic EBRT daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm I (EBRT, brachytherapy)	Questionnaire Administration	Patients undergo pelvic EBRT daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm I (EBRT, brachytherapy)	X-Ray Imaging	Patients undergo pelvic EBRT daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm II (EBRT, brachytherapy, pembrolizumab)	Biospecimen Collection	Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm II (EBRT, brachytherapy, pembrolizumab)	Brachytherapy	Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm II (EBRT, brachytherapy, pembrolizumab)	Computed Tomography	Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Arm II (EBRT, brachytherapy, pembrolizumab)	External Beam Radiation Therapy	Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.

Primary Outcome Measures

Name	Time	Method
3 year recurrence-free survival	Time from study entry (randomization) to the time of cancer recurrence, assessed at 3 years	Will be estimated using the Kaplan Meier method and treatment comparisons will be made using a stratified log-rank test.

Secondary Outcome Measures

Name	Time	Method
5 year recurrence free survival	Time from study entry (randomization) to the time of cancer recurrence, assessed at 5 years	Proportions will be compared by treatment using Fisher's exact test. This analysis may be delayed until the data are mature.
Overall survival	Duration of time from study entry to time of death or the date of last contact, assessed up to 5 years	Will be estimated using the Kaplan Meier method and treatment comparisons will be made using a stratified log-rank test.
Patient-reported outcomes	Up to 2 years after starting treatment	Will be assessed by questionnaire.
Recurrence patterns	5 years	The cumulative incidences of vaginal recurrence, pelvic recurrence, retroperitoneal, and distant recurrence from endometrial cancer will be estimated within treatment regimen. Treatments will be compared graphically using Kaplan-Meier estimates of the survival function.
Impact of circulating tumor deoxyribonucleic acid (ctDNA) on treatment outcomes	Up to 5 years	Will examine the association between ctDNA and 2- year (or 3-year) progression free survival in a 2-stages of analysis.
Incidence of adverse events	12 months	Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) by treatment regimen. Will be evaluated descriptively using frequencies and percentages and will be reported using tables. Differences between treatment arms will be assessed through absolute deviations and contingency table analyses. All patients who receive treatment, will be evaluated for toxicity. Toxicities by type and maximum grade over the course of treatment and follow up will be summarized and by date of occurrence (acute toxicity and late adverse effects).

Trial Locations

Locations (280)

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

Marshfield Medical Center - Minocqua; 🇺🇸 Minocqua, Wisconsin, United States

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

Community Cancer Institute; 🇺🇸 Clovis, California, United States

University Oncology Associates; 🇺🇸 Clovis, California, United States

John Muir Medical Center-Concord; 🇺🇸 Concord, California, United States

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

Los Angeles General Medical Center; 🇺🇸 Los Angeles, California, United States

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

UCLA / Jonsson Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

UCSF Medical Center-Mission Bay; 🇺🇸 San Francisco, California, United States

John Muir Medical Center-Walnut Creek; 🇺🇸 Walnut Creek, California, United States

UCHealth University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

Rocky Mountain Cancer Centers-Penrose; 🇺🇸 Colorado Springs, Colorado, United States

UCHealth Memorial Hospital Central; 🇺🇸 Colorado Springs, Colorado, United States

Memorial Hospital North; 🇺🇸 Colorado Springs, Colorado, United States

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

UCHealth Highlands Ranch Hospital; 🇺🇸 Highlands Ranch, Colorado, United States

Littleton Adventist Hospital; 🇺🇸 Littleton, Colorado, United States

Parker Adventist Hospital; 🇺🇸 Parker, Colorado, United States

Danbury Hospital; 🇺🇸 Danbury, Connecticut, United States

Smilow Cancer Hospital-Derby Care Center; 🇺🇸 Derby, Connecticut, United States

Smilow Cancer Hospital Care Center-Fairfield; 🇺🇸 Fairfield, Connecticut, United States

Smilow Cancer Hospital Care Center at Glastonbury; 🇺🇸 Glastonbury, Connecticut, United States

Smilow Cancer Hospital Care Center at Greenwich; 🇺🇸 Greenwich, Connecticut, United States

Smilow Cancer Hospital Care Center - Guilford; 🇺🇸 Guilford, Connecticut, United States

Smilow Cancer Hospital Care Center at Saint Francis; 🇺🇸 Hartford, Connecticut, United States

Smilow Cancer Center/Yale-New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

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

Yale-New Haven Hospital North Haven Medical Center; 🇺🇸 North Haven, Connecticut, United States

Norwalk Hospital; 🇺🇸 Norwalk, Connecticut, United States

Smilow Cancer Hospital-Orange Care Center; 🇺🇸 Orange, Connecticut, United States

Smilow Cancer Hospital-Torrington Care Center; 🇺🇸 Torrington, Connecticut, United States

Smilow Cancer Hospital Care Center-Trumbull; 🇺🇸 Trumbull, Connecticut, United States

Smilow Cancer Hospital-Waterbury Care Center; 🇺🇸 Waterbury, Connecticut, United States

Smilow Cancer Hospital Care Center - Waterford; 🇺🇸 Waterford, Connecticut, United States

GenesisCare USA - FGO; 🇺🇸 Fort Myers, Florida, United States

Regional Cancer Center-Lee Memorial Health System; 🇺🇸 Fort Myers, Florida, United States

Northside Hospital; 🇺🇸 Atlanta, Georgia, United States

Northside Hospital-Forsyth; 🇺🇸 Cumming, Georgia, United States

Wellstar Kennestone Hospital; 🇺🇸 Marietta, Georgia, United States

CTCA at Southeastern Regional Medical Center; 🇺🇸 Newnan, Georgia, United States

Memorial Health University Medical Center; 🇺🇸 Savannah, Georgia, United States

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler; 🇺🇸 Savannah, Georgia, United States

Hawaii Cancer Care - Westridge; 🇺🇸 'Aiea, Hawaii, United States

Pali Momi Medical Center; 🇺🇸 'Aiea, Hawaii, United States

Hawaii Cancer Care Inc - Waterfront Plaza; 🇺🇸 Honolulu, Hawaii, United States

Queen's Cancer Cenrer - POB I; 🇺🇸 Honolulu, Hawaii, United States

Queen's Medical Center; 🇺🇸 Honolulu, Hawaii, United States

Straub Clinic and Hospital; 🇺🇸 Honolulu, Hawaii, United States

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

Hawaii Cancer Care Inc-Liliha; 🇺🇸 Honolulu, Hawaii, United States

Queen's Cancer Center - Kuakini; 🇺🇸 Honolulu, Hawaii, United States

The Cancer Center of Hawaii-Liliha; 🇺🇸 Honolulu, Hawaii, United States

Kapiolani Medical Center for Women and Children; 🇺🇸 Honolulu, Hawaii, United States

Wilcox Memorial Hospital and Kauai Medical Clinic; 🇺🇸 Lihue, Hawaii, United States

Saint Luke's Cancer Institute - Boise; 🇺🇸 Boise, Idaho, United States

Saint Luke's Cancer Institute - Fruitland; 🇺🇸 Fruitland, Idaho, United States

Saint Luke's Cancer Institute - Meridian; 🇺🇸 Meridian, Idaho, United States

Saint Luke's Cancer Institute - Nampa; 🇺🇸 Nampa, Idaho, United States

Saint Luke's Cancer Institute - Twin Falls; 🇺🇸 Twin Falls, Idaho, United States

Centralia Oncology Clinic; 🇺🇸 Centralia, Illinois, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

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

Cancer Care Specialists of Illinois - Decatur; 🇺🇸 Decatur, Illinois, United States

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

Crossroads Cancer Center; 🇺🇸 Effingham, Illinois, United States

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

Northwestern Medicine Cancer Center Delnor; 🇺🇸 Geneva, Illinois, United States

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

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

Northwestern Medicine Lake Forest Hospital; 🇺🇸 Lake Forest, Illinois, United States

Loyola University Medical Center; 🇺🇸 Maywood, Illinois, United States

UC Comprehensive Cancer Center at Silver Cross; 🇺🇸 New Lenox, Illinois, United States

Cancer Care Center of O'Fallon; 🇺🇸 O'Fallon, Illinois, United States

University of Chicago Medicine-Orland Park; 🇺🇸 Orland Park, Illinois, United States

Southern Illinois University School of Medicine; 🇺🇸 Springfield, Illinois, United States

Springfield Clinic; 🇺🇸 Springfield, Illinois, United States

Northwestern Medicine Cancer Center Warrenville; 🇺🇸 Warrenville, Illinois, United States

Midwestern Regional Medical Center; 🇺🇸 Zion, Illinois, United States

Ascension Saint Vincent Indianapolis Hospital; 🇺🇸 Indianapolis, Indiana, United States

Mary Greeley Medical Center; 🇺🇸 Ames, Iowa, United States

McFarland Clinic - Ames; 🇺🇸 Ames, Iowa, United States

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

Saint Elizabeth Healthcare Edgewood; 🇺🇸 Edgewood, Kentucky, United States

Baptist Health Lexington; 🇺🇸 Lexington, Kentucky, United States

Baptist Health Louisville; 🇺🇸 Louisville, Kentucky, United States

East Jefferson General Hospital; 🇺🇸 Metairie, Louisiana, United States

Louisiana State University Health Science Center; 🇺🇸 New Orleans, Louisiana, United States

University Medical Center New Orleans; 🇺🇸 New Orleans, Louisiana, United States

MaineHealth Coastal Cancer Treatment Center; 🇺🇸 Bath, Maine, United States

MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford; 🇺🇸 Biddeford, Maine, United States

Maine Medical Center-Bramhall Campus; 🇺🇸 Portland, Maine, United States

MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford; 🇺🇸 Sanford, Maine, United States

Maine Medical Center- Scarborough Campus; 🇺🇸 Scarborough, Maine, United States

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

Corewell Health Dearborn Hospital; 🇺🇸 Dearborn, Michigan, United States

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

Weisberg Cancer Treatment Center; 🇺🇸 Farmington Hills, Michigan, United States

Corewell Health William Beaumont University Hospital; 🇺🇸 Royal Oak, Michigan, United States

Corewell Health Beaumont Troy Hospital; 🇺🇸 Troy, Michigan, United States

Minnesota Oncology - Burnsville; 🇺🇸 Burnsville, Minnesota, United States

Mercy Hospital; 🇺🇸 Coon Rapids, Minnesota, United States

Fairview Southdale Hospital; 🇺🇸 Edina, Minnesota, United States

Unity Hospital; 🇺🇸 Fridley, Minnesota, United States

Minnesota Oncology Hematology PA-Maplewood; 🇺🇸 Maplewood, Minnesota, United States

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

Monticello Cancer Center; 🇺🇸 Monticello, Minnesota, United States

Coborn Cancer Center at Saint Cloud Hospital; 🇺🇸 Saint Cloud, Minnesota, United States

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

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

Ridgeview Medical Center; 🇺🇸 Waconia, Minnesota, United States

Rice Memorial Hospital; 🇺🇸 Willmar, Minnesota, United States

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

Parkland Health Center - Farmington; 🇺🇸 Farmington, Missouri, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

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

Missouri Baptist Medical Center; 🇺🇸 Saint Louis, Missouri, United States

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

Sainte Genevieve County Memorial Hospital; 🇺🇸 Sainte Genevieve, Missouri, United States

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

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

Missouri Baptist Sullivan Hospital; 🇺🇸 Sullivan, Missouri, United States

BJC Outpatient Center at Sunset Hills; 🇺🇸 Sunset Hills, Missouri, United States

Billings Clinic Cancer Center; 🇺🇸 Billings, Montana, United States

Bozeman Health Deaconess Hospital; 🇺🇸 Bozeman, Montana, United States

Community Medical Center; 🇺🇸 Missoula, Montana, United States

Nebraska Cancer Specialists/Oncology Hematology West PC - MECC; 🇺🇸 Omaha, Nebraska, United States

Nebraska Methodist Hospital; 🇺🇸 Omaha, Nebraska, United States

Oncology Associates PC; 🇺🇸 Omaha, Nebraska, United States

Alegent Health Bergan Mercy Medical Center; 🇺🇸 Omaha, Nebraska, United States

Women's Cancer Center of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Memorial Sloan Kettering Basking Ridge; 🇺🇸 Basking Ridge, New Jersey, United States

Cooper Hospital University Medical Center; 🇺🇸 Camden, New Jersey, United States

Memorial Sloan Kettering Monmouth; 🇺🇸 Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen; 🇺🇸 Montvale, New Jersey, United States

Virtua Samson Cancer Center; 🇺🇸 Moorestown, New Jersey, United States

Jersey Shore Medical Center; 🇺🇸 Neptune, New Jersey, United States

Virtua Voorhees; 🇺🇸 Voorhees, New Jersey, United States

University of New Mexico Cancer Center; 🇺🇸 Albuquerque, New Mexico, United States

Women's Cancer Care Associates LLC; 🇺🇸 Albany, New York, United States

New York-Presbyterian/Brooklyn Methodist Hospital; 🇺🇸 Brooklyn, New York, United States

Memorial Sloan Kettering Commack; 🇺🇸 Commack, New York, United States

The New York Hospital Medical Center of Queens; 🇺🇸 Flushing, New York, United States

Memorial Sloan Kettering Westchester; 🇺🇸 Harrison, New York, United States

Northwell Health/Center for Advanced Medicine; 🇺🇸 Lake Success, New York, United States

NYU Langone Hospital - Long Island; 🇺🇸 Mineola, New York, United States

Long Island Jewish Medical Center; 🇺🇸 New Hyde Park, New York, United States

Mount Sinai Chelsea; 🇺🇸 New York, New York, United States

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

Mount Sinai West; 🇺🇸 New York, New York, United States

Mount Sinai Hospital; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

NYP/Weill Cornell Medical Center; 🇺🇸 New York, New York, United States

Highland Hospital; 🇺🇸 Rochester, New York, United States

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

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

Memorial Sloan Kettering Nassau; 🇺🇸 Uniondale, New York, United States

UNC Lineberger Comprehensive Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States

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

Cone Health Cancer Center; 🇺🇸 Greensboro, North Carolina, United States

Duke Women's Cancer Care Raleigh; 🇺🇸 Raleigh, North Carolina, United States

Duke Raleigh Hospital; 🇺🇸 Raleigh, North Carolina, United States

Sanford Bismarck Medical Center; 🇺🇸 Bismarck, North Dakota, United States

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

Sanford Roger Maris Cancer Center; 🇺🇸 Fargo, North Dakota, United States

UHHS-Chagrin Highlands Medical Center; 🇺🇸 Beachwood, Ohio, United States

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

Dayton Physicians LLC-Miami Valley South; 🇺🇸 Centerville, Ohio, United States

Miami Valley Hospital South; 🇺🇸 Centerville, Ohio, United States

Geauga Hospital; 🇺🇸 Chardon, Ohio, United States

Good Samaritan Hospital - Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Bethesda North Hospital; 🇺🇸 Cincinnati, Ohio, United States

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

MetroHealth Medical Center; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Cancer Center/Fairview Hospital; 🇺🇸 Cleveland, Ohio, United States

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

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

Mount Carmel East Hospital; 🇺🇸 Columbus, Ohio, United States

Riverside Methodist Hospital; 🇺🇸 Columbus, Ohio, United States

The Mark H Zangmeister Center; 🇺🇸 Columbus, Ohio, United States

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

Dayton Physician LLC - Englewood; 🇺🇸 Dayton, Ohio, United States

Miami Valley Hospital North; 🇺🇸 Dayton, Ohio, United States

Dublin Methodist Hospital; 🇺🇸 Dublin, Ohio, United States

Atrium Medical Center-Middletown Regional Hospital; 🇺🇸 Franklin, Ohio, United States

Dayton Physicians LLC-Atrium; 🇺🇸 Franklin, Ohio, United States

Mount Carmel Grove City Hospital; 🇺🇸 Grove City, Ohio, United States

Hillcrest Hospital Cancer Center; 🇺🇸 Mayfield Heights, Ohio, United States

Mount Carmel New Albany Surgical Hospital; 🇺🇸 New Albany, Ohio, United States

University Hospitals Sharon Health Center; 🇺🇸 Wadsworth, Ohio, United States

UH Seidman Cancer Center at Lake Health Mentor Campus; 🇺🇸 Mentor, Ohio, United States

Saint Ann's Hospital; 🇺🇸 Westerville, Ohio, United States

UH Seidman Cancer Center at Saint John Medical Center; 🇺🇸 Westlake, Ohio, United States

UHHS-Westlake Medical Center; 🇺🇸 Westlake, Ohio, United States

Genesis Healthcare System Cancer Care Center; 🇺🇸 Zanesville, Ohio, United States

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

Mercy Hospital Oklahoma City; 🇺🇸 Oklahoma City, Oklahoma, United States

Clackamas Radiation Oncology Center; 🇺🇸 Clackamas, Oregon, United States

Providence Cancer Institute Clackamas Clinic; 🇺🇸 Clackamas, Oregon, United States

Legacy Mount Hood Medical Center; 🇺🇸 Gresham, Oregon, United States

Providence Newberg Medical Center; 🇺🇸 Newberg, Oregon, United States

Legacy Good Samaritan Hospital and Medical Center; 🇺🇸 Portland, Oregon, United States

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

Providence Saint Vincent Medical Center; 🇺🇸 Portland, Oregon, United States

Legacy Meridian Park Hospital; 🇺🇸 Tualatin, Oregon, United States

Carlisle Regional Cancer Center; 🇺🇸 Carlisle, Pennsylvania, United States

Ephrata Cancer Center; 🇺🇸 Ephrata, Pennsylvania, United States

Adams Cancer Center; 🇺🇸 Gettysburg, Pennsylvania, United States

UPMC Cancer Centers - Arnold Palmer Pavilion; 🇺🇸 Greensburg, Pennsylvania, United States

UPMC Pinnacle Cancer Center/Community Osteopathic Campus; 🇺🇸 Harrisburg, Pennsylvania, United States

Lancaster General Ann B Barshinger Cancer Institute; 🇺🇸 Lancaster, Pennsylvania, United States

Lancaster General Hospital; 🇺🇸 Lancaster, Pennsylvania, United States

Sechler Family Cancer Center; 🇺🇸 Lebanon, Pennsylvania, United States

UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion; 🇺🇸 Mechanicsburg, Pennsylvania, United States

Paoli Memorial Hospital; 🇺🇸 Paoli, Pennsylvania, United States

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

Pennsylvania Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

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

UPMC-Magee Womens Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

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

Asplundh Cancer Pavilion; 🇺🇸 Willow Grove, Pennsylvania, United States

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

WellSpan Health-York Cancer Center; 🇺🇸 York, Pennsylvania, United States

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

Women and Infants Hospital; 🇺🇸 Providence, Rhode Island, United States

Smilow Cancer Hospital Care Center - Westerly; 🇺🇸 Westerly, Rhode Island, United States

Saint Joseph's/Candler - Bluffton Campus; 🇺🇸 Bluffton, South Carolina, United States

Saint Francis Hospital; 🇺🇸 Greenville, South Carolina, United States

Prisma Health Cancer Institute - Faris; 🇺🇸 Greenville, South Carolina, United States

Saint Francis Cancer Center; 🇺🇸 Greenville, South Carolina, United States

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

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

Avera Cancer Institute; 🇺🇸 Sioux Falls, South Dakota, United States

Sanford USD Medical Center - Sioux Falls; 🇺🇸 Sioux Falls, South Dakota, United States

MD Anderson in The Woodlands; 🇺🇸 Conroe, Texas, United States

Parkland Memorial Hospital; 🇺🇸 Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas; 🇺🇸 Dallas, Texas, United States

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center; 🇺🇸 Houston, Texas, United States

Ben Taub General Hospital; 🇺🇸 Houston, Texas, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Methodist Willowbrook Hospital; 🇺🇸 Houston, Texas, United States

MD Anderson West Houston; 🇺🇸 Houston, Texas, United States

Houston Methodist West Hospital; 🇺🇸 Houston, Texas, United States

MD Anderson League City; 🇺🇸 League City, Texas, United States

MD Anderson in Sugar Land; 🇺🇸 Sugar Land, Texas, United States

Houston Methodist Sugar Land Hospital; 🇺🇸 Sugar Land, Texas, United States

Houston Methodist The Woodlands Hospital; 🇺🇸 The Woodlands, Texas, United States

Farmington Health Center; 🇺🇸 Farmington, Utah, United States

University of Utah Sugarhouse Health Center; 🇺🇸 Salt Lake City, Utah, United States

Huntsman Cancer Institute/University of Utah; 🇺🇸 Salt Lake City, Utah, United States

VCU Massey Cancer Center at Stony Point; 🇺🇸 Richmond, Virginia, United States

Virginia Commonwealth University/Massey Cancer Center; 🇺🇸 Richmond, Virginia, United States

Carilion Clinic Gynecological Oncology; 🇺🇸 Roanoke, Virginia, United States

Legacy Salmon Creek Hospital; 🇺🇸 Vancouver, Washington, United States

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

Ascension Southeast Wisconsin Hospital - Elmbrook Campus; 🇺🇸 Brookfield, Wisconsin, United States

Marshfield Medical Center-EC Cancer Center; 🇺🇸 Eau Claire, Wisconsin, United States

Ascension Saint Francis - Reiman Cancer Center; 🇺🇸 Franklin, Wisconsin, United States

Ascension Southeast Wisconsin Hospital - Franklin; 🇺🇸 Franklin, Wisconsin, United States

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

University of Wisconsin Carbone Cancer Center - University Hospital; 🇺🇸 Madison, Wisconsin, United States

Marshfield Medical Center-Marshfield; 🇺🇸 Marshfield, Wisconsin, United States

Ascension Columbia Saint Mary's Hospital Ozaukee; 🇺🇸 Mequon, Wisconsin, United States

Ascension Southeast Wisconsin Hospital - Saint Joseph Campus; 🇺🇸 Milwaukee, Wisconsin, United States

Ascension Columbia Saint Mary's Hospital - Milwaukee; 🇺🇸 Milwaukee, Wisconsin, United States

Ascension Saint Francis Hospital; 🇺🇸 Milwaukee, Wisconsin, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Ascension All Saints Hospital; 🇺🇸 Racine, Wisconsin, United States

Marshfield Medical Center-Rice Lake; 🇺🇸 Rice Lake, Wisconsin, United States

Marshfield Medical Center-River Region at Stevens Point; 🇺🇸 Stevens Point, Wisconsin, United States

Ascension Medical Group Southeast Wisconsin - Mayfair Road; 🇺🇸 Wauwatosa, Wisconsin, United States

Marshfield Medical Center - Weston; 🇺🇸 Weston, Wisconsin, United States

Cancer Center-Metro Medical Center Bayamon; 🇵🇷 Bayamon, Puerto Rico

Doctors Cancer Center; 🇵🇷 Manati, Puerto Rico

San Juan Community Oncology Group; 🇵🇷 San Juan, Puerto Rico

Centro Comprensivo de Cancer de UPR; 🇵🇷 San Juan, Puerto Rico

San Juan City Hospital; 🇵🇷 San Juan, Puerto Rico