Testing Nivolumab and Ipilimumab Immunotherapy With or Without the Targeted Drug Cabozantinib in Recurrent, Metastatic, or Incurable Nasopharyngeal Cancer
- Conditions
- Metastatic Nasopharyngeal CarcinomaRecurrent Nasopharyngeal CarcinomaStage IV Nasopharyngeal Carcinoma AJCC v8
- Interventions
- Procedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: Magnetic Resonance Imaging
- Registration Number
- NCT05904080
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II trial tests how well nivolumab and ipilimumab immunotherapy with or without cabozantinib works in treating patients with nasopharyngeal cancer that has come back (after a period of improvement) (recurrent), has spread from where it first started (primary site) to other places in the body (metastatic), or for which no treatment is currently available (incurable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving immunotherapy with nivolumab and ipilimumab and targeted therapy with cabozantinib may help shrink and stabilize nasopharyngeal cancer.
- Detailed Description
PRIMARY OBJECTIVE:
I. To determine if the progression-free survival (PFS) of the triplet combination (cabozantinib S-malate, nivolumab, and ipilimumab \[CaboNivoIpi\]) is more favorable than the doublet (nivolumab and ipilimumab \[NivoIpi\]).
SECONDARY OBJECTIVES:
I. To compare safety and tolerability between the two arms (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5.0.).
II. To compare overall response rate (ORR) between the two arms via both Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST) criteria.
III. To compare overall survival (OS) between the two arms. IV. To assess response by primary or acquired PD-1/L1 inhibitor resistance in the prior line of therapy.
EXPLORATORY OBJECTIVE:
I. To evaluate molecular and immunologic predictors of response (Epstein-Barr virus \[EBV\] viral load; PD-L1 score) between arms.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and collection of blood samples throughout the trial.
ARM B: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 and cabozantinib S-malate orally (PO) daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may continue with cabozantinib S-malate after 2 years per treating investigator. Patients undergo CT or MRI and collection of blood samples throughout the trial.
After completion of study treatment, patients are followed up every 8-12 weeks until progression of disease occurs or a new non-protocol anti-cancer therapy is initiated and then every 6 months for up to 2 years.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
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Patients must have histologically documented nasopharyngeal carcinoma (NPC) regardless of World Health Organization (WHO) classification (keratinizing squamous cell carcinoma, non-keratinizing, or basaloid squamous cell carcinoma) and regardless of association with Epstein-Barr virus (EBV) and/or human papillomavirus (HPV)
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Recurrent, metastatic and incurable disease treated with platinum-gemcitabine and prior PD-1/L1 blockade (as first or second-line therapy) where immunotherapy was part of the most recent prior line of therapy
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Patients are eligible regardless of prior smoking history, p16 immunohistochemistry (IHC) status, PD-L1 expression status, EBV tumor status, EBV viral load at baseline, or tumor genomic alteration status
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Patients must have at least one measurable lesion (by RECIST v1.1) which has not been previously irradiated that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions as >= 10 mm (>= 1 cm) (and short axis for nodal lesions, LN >= 15 mm) with CT scan, MRI, or calipers by clinical exam
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Patients may have had no more than 2 prior lines of prior systemic therapy for recurrent, metastatic NPC
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No prior VEGFR targeted therapy permitted
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Age >= 18 years
-
Eastern Cooperative Oncology Group Performance (ECOG) performance status 0-2
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Absolute neutrophil count (ANC) >= 1,000/mm^3
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Hemoglobin >= 9 g/dL
-
Platelet count >= 100,000/mm^3
-
Creatinine or creatinine clearance =< 1.5 mg/dL or >= 30 Modification of Diet in Renal Disease (MDRD)
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Total bilirubin =< 1.5 x institutional upper limit of normal (ULN); except subjects with Gilbert syndrome who can have a total bilirubin < 3 mg/dL
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Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGT]) =< 3 x upper limit of normal (ULN)
- Up to =< 5 allowed with liver metastases
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Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test, per institution standard, done =< 7 days prior to registration is required.
- Pregnant women are excluded from this study because nivolumab, ipilimumab, and cabozantinib are all Class C or D agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants, secondary to treatment of the mother with any of the study agents, breastfeeding should be discontinued if the mother is treated with as part of this study (in either arm)
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No active tumor bleeding: or radiographic evidence of major blood vessel infiltration as judged by the treating investigator
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Prior -anti-cancer therapy is allowed: Patients need to be recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1), with the exception of alopecia. Any life-threatening events clearly attributable to prior immunotherapy exposure that have a high possibility of recurring should warrant exclusion: including severe pneumonitis, grade 4 bullous dermatitis/drug reaction with eosinophilia and systemic symptoms (DRESS), neurologic events such as autoimmune encephalitis transverse myelitis, and/or myocarditis. Maintenance hormonal replacement or long-term hormonal therapy exposure is permitted.
-
No chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration. Palliative (limited-field) radiation therapy is permitted, if all of the following criteria are met:
- Repeat imaging demonstrates no new sites of bone metastases.
- The lesion being considered for palliative radiation is not a target lesion
-
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No patients with a prior malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
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Brain metastases allowed: Patients with treated brain metastases are eligible if follow-up brain imaging 3 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
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Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
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For patients with evidence of chronic hepatitis B (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 receiving treatment, they are eligible if they have an undetectable HCV viral load
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Solid organ or tissue transplant is allowed: - subsequent therapy with nivolumab increases the risk of organ/tissue rejection. Patients must be instructed that it is crucial they stay in touch with their transplant team during treatment
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No active autoimmune disease: or history of autoimmune disease that might recur, and which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of
- Immune related neurologic disease,
- Multiple sclerosis,
- Autoimmune (demyelinating) neuropathy,
- Guillain-Barre syndrome (GBS),
- Myasthenia gravis;
- Systemic autoimmune disease such as SLE,
- Connective tissue diseases,
- Scleroderma, inflammatory bowel disease (IBD),
- Crohn's, ulcerative colitis,
- Patients with a history of toxic epidermal necrolysis (TEN),
- Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease
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Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible
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Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome, and psoriasis controlled with topical medication and patients with only positive serology, such as antinuclear antibodies (ANA) or anti-thyroid antibodies, should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
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Pneumonitis should be evaluated for the nature of the disease process, need for treatment prior study treatment, and the risk of exacerbation with study treatment
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Able to swallow oral medication: No known medical condition causing an inability to swallow oral formulations of agents
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No condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study registration. Patients are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses > 10 mg daily prednisone are permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by a contact allergen) is permitted
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Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel) is prohibited. Allowed anticoagulants are the following:
- Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
- Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
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Concomitant use of any medications or substances that are strong inhibitors or inducers of CYP3A4 is discouraged; if unavoidable, the dose of cabozantinib on study should be adjusted accordingly. Any complementary medications (e.g., herbal supplements or traditional Chinese medicines) intended to treat the disease under study are prohibited
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B (nivolumab, ipilimumab, cabozantinib) Cabozantinib S-malate Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 and cabozantinib S-malate PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may continue with cabozantinib S-malate after 2 years per treating investigator. Patients undergo CT or MRI and collection of blood samples throughout the trial. Arm A (nivolumab, ipilimumab) Biospecimen Collection Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and collection of blood samples throughout the trial. Arm A (nivolumab, ipilimumab) Computed Tomography Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and collection of blood samples throughout the trial. Arm A (nivolumab, ipilimumab) Ipilimumab Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and collection of blood samples throughout the trial. Arm A (nivolumab, ipilimumab) Magnetic Resonance Imaging Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and collection of blood samples throughout the trial. Arm A (nivolumab, ipilimumab) Nivolumab Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and collection of blood samples throughout the trial. Arm B (nivolumab, ipilimumab, cabozantinib) Biospecimen Collection Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 and cabozantinib S-malate PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may continue with cabozantinib S-malate after 2 years per treating investigator. Patients undergo CT or MRI and collection of blood samples throughout the trial. Arm B (nivolumab, ipilimumab, cabozantinib) Computed Tomography Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 and cabozantinib S-malate PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may continue with cabozantinib S-malate after 2 years per treating investigator. Patients undergo CT or MRI and collection of blood samples throughout the trial. Arm B (nivolumab, ipilimumab, cabozantinib) Ipilimumab Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 and cabozantinib S-malate PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may continue with cabozantinib S-malate after 2 years per treating investigator. Patients undergo CT or MRI and collection of blood samples throughout the trial. Arm B (nivolumab, ipilimumab, cabozantinib) Magnetic Resonance Imaging Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 and cabozantinib S-malate PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may continue with cabozantinib S-malate after 2 years per treating investigator. Patients undergo CT or MRI and collection of blood samples throughout the trial. Arm B (nivolumab, ipilimumab, cabozantinib) Nivolumab Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 and cabozantinib S-malate PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may continue with cabozantinib S-malate after 2 years per treating investigator. Patients undergo CT or MRI and collection of blood samples throughout the trial.
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) From randomization to the first of either progression or death from any cause, or censored at last known tumor assessment date, assessed up to 2 years PFS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.
- Secondary Outcome Measures
Name Time Method Overall survival (OS) From randomization to death from any cause, or censored at last known follow-up, assessed up to 2 years OS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.
Response by subgroups of interest Up to 2 years Will also report and compare the overall response rate (ORR) between different subgroups of interest (primary or acquired PD-1/L1 inhibitor resistance in the prior line of therapy (further defined below), etc.). These comparisons will be done via chi-square or Fisher's exact tests. We'll also assess primary versus acquired resistance to prior PD-1 inhibition in each arm as well. While not a formal stratification, in the interim and final analysis we'll also descriptively assess these subgroups between arms as well.
Incidence of adverse events Up to 2 years The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events version 5.0. The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms. Comparisons between arms will be made by using either the chi-square or Fisher's exact test.
ORR Up to 2 years The response rate will be compared via chi-square or Fisher's exact tests between the 2 treatment arms using both the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and also separately for the immune-modified RECIST criteria.
Predictors of response Up to 2 years Will correlate the baseline data (Epstein-Barr virus viral load, p16 immunohistochemistry status, smoking history, and PD-L1 score) with ORR data. For this analysis, logistic regression models will be assessed using the baseline data to predict binary response data. Odds ratios and 95% confidence intervals will be reported. Will also summarize the data using descriptive statistics and graphical methods.
Trial Locations
- Locations (81)
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
🇺🇸Irvine, California, United States
Keck Medicine of USC Koreatown
🇺🇸Los Angeles, California, United States
Los Angeles General Medical Center
🇺🇸Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
USC Norris Oncology/Hematology-Newport Beach
🇺🇸Newport Beach, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Stanford Cancer Institute Palo Alto
🇺🇸Palo Alto, California, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸Boise, Idaho, United States
Saint Alphonsus Cancer Care Center-Caldwell
🇺🇸Caldwell, Idaho, United States
Kootenai Health - Coeur d'Alene
🇺🇸Coeur d'Alene, Idaho, United States
Saint Alphonsus Cancer Care Center-Nampa
🇺🇸Nampa, Idaho, United States
Kootenai Clinic Cancer Services - Post Falls
🇺🇸Post Falls, Idaho, United States
Kootenai Clinic Cancer Services - Sandpoint
🇺🇸Sandpoint, Idaho, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Northwestern Medicine Cancer Center Kishwaukee
🇺🇸DeKalb, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
Northwestern Medicine Glenview Outpatient Center
🇺🇸Glenview, Illinois, United States
Northwestern Medicine Grayslake Outpatient Center
🇺🇸Grayslake, Illinois, United States
Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Northwestern Medicine Lake Forest Hospital
🇺🇸Lake Forest, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
🇺🇸New Lenox, Illinois, United States
Northwestern Medicine Orland Park
🇺🇸Orland Park, Illinois, United States
University of Chicago Medicine-Orland Park
🇺🇸Orland Park, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
🇺🇸Ankeny, Iowa, United States
Mercy Cancer Center-West Lakes
🇺🇸Clive, Iowa, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
🇺🇸Clive, Iowa, United States
Heartland Oncology and Hematology LLP
🇺🇸Council Bluffs, Iowa, United States
Methodist Jennie Edmundson Hospital
🇺🇸Council Bluffs, Iowa, United States
Nebraska Cancer Specialists/Oncology Hematology West PC - MEJ
🇺🇸Council Bluffs, Iowa, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
🇺🇸Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
🇺🇸Des Moines, Iowa, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Sanford Joe Lueken Cancer Center
🇺🇸Bemidji, Minnesota, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
Community Hospital of Anaconda
🇺🇸Anaconda, Montana, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Bozeman Health Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Logan Health Medical Center
🇺🇸Kalispell, 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
Memorial Sloan Kettering Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
🇺🇸Montvale, New Jersey, United States
Memorial Sloan Kettering Commack
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Westchester
🇺🇸Harrison, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Nassau
🇺🇸Uniondale, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, 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
Good Samaritan Hospital - Cincinnati
🇺🇸Cincinnati, Ohio, United States
Cancer Centers of Southwest Oklahoma Research
🇺🇸Lawton, Oklahoma, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
🇺🇸Tulsa, Oklahoma, United States
Saint Alphonsus Cancer Care Center-Ontario
🇺🇸Ontario, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Sanford Cancer Center Oncology Clinic
🇺🇸Sioux Falls, South Dakota, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
Camden Clark Medical Center
🇺🇸Parkersburg, West Virginia, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Marshfield Medical Center - Minocqua
🇺🇸Minocqua, 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
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States