Testing the Addition of the Anti-cancer Drug, Cabozantinib, to the Usual Immunotherapy Treatment, Avelumab, in Patients With Metastatic Urothelial Cancer, MAIN-CAV Study

Phase 3

Active, not recruiting

• Conditions: Metastatic Bladder Urothelial Carcinoma; Advanced Renal Pelvis Urothelial Carcinoma; Advanced Ureter Urothelial Carcinoma; Stage III Urethral Cancer AJCC v8; Metastatic Renal Pelvis Urothelial Carcinoma; Stage IV Renal Pelvis and Ureter Cancer AJCC v8; Stage IV Renal Pelvis Cancer AJCC v8; Stage IV Ureter Cancer AJCC v8; Stage IV Urethral Cancer AJCC v8; Advanced Bladder Urothelial Carcinoma
• Interventions: Drug: Avelumab; Procedure: Biospecimen Collection; Procedure: Bone Scan; Drug: Cabozantinib S-malate; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

• Registration Number: NCT05092958
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This phase III trial compares the effect of adding cabozantinib to avelumab versus avelumab alone in treating patients with urothelial cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib and avelumab together may further shrink the cancer or prevent it from returning/progressing.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the effect of cabozantinib (cabozantinib S-malate) in combination with avelumab on overall survival (OS) compared to avelumab alone in patients with metastatic urothelial cancer (mUC) who did not progress during first-line platinum-based chemotherapy therapy, i.e. patients who had complete response (CR), partial response (PR) or stable disease (SD) after completion of first line platinum-based chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate the effect of cabozantinib in combination with avelumab on progression-free survival (PFS) compared to avelumab alone for maintenance treatment following initial first-line treatment in patients who had a CR, PR or SD upon completion of first-line platinum-based chemotherapy.

II. To evaluate the safety and tolerability of cabozantinib in combination with avelumab in mUC compared to avelumab alone for maintenance treatment following initial first-line treatment in patients who had a CR, PR or SD upon completion of first-line platinum-based chemotherapy.

III. To evaluate activity of cabozantinib in combination with avelumab based on Response Evaluation Criteria in Solid Tumors (RECIST) compared to avelumab alone for maintenance treatment following initial first-line treatment in patients who had a CR, PR or SD upon completion of first-line platinum-based chemotherapy.

IV. Results of the primary analysis will be examined for consistency, while accounting for the stratification factors and/or covariates of baseline quality of life (QOL) and fatigue.

V. To evaluate the activity of cabozantinib in combination with avelumab compared to avelumab alone based on PD-L1 status of patients' tumors.

QUALITY OF LIFE (QOL) OBJECTIVES:

I. To compare quality-adjusted survival between patients randomized to receive cabozantinib and avelumab versus (vs.) avelumab alone using the European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ-5D-5L).

II. To compare patient-reported fatigue as assessed by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue 4a from baseline through 12 months between patients randomized to receive cabozantinib and avelumab vs. avelumab alone.

III. To compare patient-reported global health status/quality of life as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core (C)30 from baseline through 12 months between patients randomized to receive cabozantinib and avelumab vs. avelumab alone.

IV. To compare scale scores of the EORTC QLQ-Bladder Cancer Muscle-Invasive (BLM)30 (urinary symptoms, urostomy problems, catheter problems, future perspectives, abdominal bloating and flatulence, body image, sexual function) at 3, 6, 12, 18, and 24 months between patients randomized to receive cabozantinib and avelumab vs. avelumab alone.

V. To compare scale scores of the EORTC QLQ-C30 (global health status/quality of life; physical, role, emotional, cognitive, and social function; symptoms) at 3, 6, 12, 18, and 24 months between patients randomized to receive cabozantinib and avelumab vs. avelumab alone.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive avelumab intravenously (IV) over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo computed tomography (CT) or magnetic resonance imaging (MRI) and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.

ARM B: Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle and cabozantinib orally (PO) daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.

After completion of study treatment, patients are followed every 30 days through 90 days, then every 3 months for 5 years.

Study Timeline

• Study First Submitted: 2021-10-22
• Study First Submitted QC: 2021-10-22
• Study First Posted: 2021-10-26
• Study Start: 2022-06-03
• Status Verified: 2024-12
• Last Update Submitted: 2025-03-14
• Last Update Posted: 2025-03-17
• Primary Completion: 2025-12-10
• Study Completion: 2025-12-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 654

Inclusion Criteria

• Histologically or cytologically-confirmed diagnosis of advanced or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra (transitional cell and mixed transitional/non-transitional cell histologies except for small-cell histology), including N3 only disease prior to start of first-line platinum-based chemotherapy

• Prior first-line treatment must have consisted of 4-6 cycles of 1st-line therapy (platinum-based chemotherapy; gemcitabine-cisplatin, gemcitabine-carboplatin, methotrexate, vinblastine, doxorubicin and cisplatin [MVAC] or dose-dense [dd]MVAC)

• No more than 1 line of prior chemotherapy for metastatic or locally advanced disease (neoadjuvant or adjuvant chemotherapy will be allowed if given 12 or more months prior to registration)

• Tumor objective response of CR, PR, or SD upon completion of first line platinum-based chemotherapy by treating physician's assessment

• The last dose of first-line chemotherapy must have been received no less than 3 weeks, and no more than 10 weeks, prior to randomization in the present study

• No prior immunotherapy with IL-2, IFN-alpha, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways

• Age >= 18 years

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

• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects

• Women of childbearing potential must have a negative pregnancy test =< 14 days prior to registration.

  • Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post menopause is defined as amenorrhea >= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason

• No use of immunosuppressive medication within 7 days prior to randomization except:

  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection);
  • Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent;
  • Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• Patients with diabetes type I, vitiligo, psoriasis, or hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible

• None of the following:

  • Active autoimmune disease that might deteriorate when receiving the anti PD-L1 agent, avelumab.

  • No known symptomatic central nervous system (CNS) metastases. Patients with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to randomization, have discontinued corticosteroid treatment for at least 2 weeks, and are neurologically stable. Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility.

  • No major surgery within 4 weeks prior to randomization. Subjects must have complete wound healing from surgery before randomization. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.

  • No palliative radiotherapy within 48 hours prior to patient randomization.

  • No hemoptysis of ≥ 0.5 teaspoon (2.5 mL) of red blood, clinically significant hematuria, hematemesis, coagulopathy, or other history of significant bleeding (eg. Pulmonary hemorrhage) within 3 months before randomization.

  • No known cavitating pulmonary lesion(s) or known endobronchial disease manifestation.

  • No administration of a live, attenuated vaccine within 30 days prior to randomization. The use of inactivated (killed) vaccines for the prevention of infectious disease is permitted. The use of COVID-19 vaccines is permitted.

  • No uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

    • Cardiovascular disorders including:

      • Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening.
      • Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
      • The patient has a known history of corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms and confirmed by electrocardiogram (ECG) within 28 days before randomization. Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is ≤ 500 ms, the subject meets eligibility in this regard.
      • Any history of congenital long QT syndrome.
      • Stroke, transient ischemic attack (TIA), myocardial infarction, or other symptomatic ischemic event or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism [DVT/PE]) within 6 months before randomization. Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if asymptomatic and stable at screening and treated with low molecular weight heparin (LMWH) or the direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban for at least 1 week before randomization. Non-symptomatic white matter disease in the brain is acceptable.

    • No significant gastrointestinal disorders, particularly those associated with a high risk of perforation or fistula formation including unresolved active peptic ulcer disease, cholecystitis, diverticultis, symptomatic cholangitis or appendicitis, or malabsorption syndrome within 28 days of randomization.

    • No other clinically significant disorders such as:

      • Any active infection requiring systemic treatment within 14 days before randomization. Subjects receiving oral (including prophylactic) antibiotics with no symptoms of infection at randomization are eligible.
      • Serious non-healing wound/ulcer/bone fracture within 28 days before randomization
      • History of organ or allogeneic stem cell transplant

    • No persisting toxicity related to prior therapy grade > 2 constituting a safety risk based on the investigator's judgment.

    • No diagnosis of any other malignancy within 3 years prior to randomization, except for locally curable cancers that have been adequately treated such as basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, Gleason < 7 prostate cancer on surveillance without any plans for treatment intervention (eg, surgery, radiation, or castration), or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms and no indication for treatment.

    • No 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).

      • 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

• Absolute neutrophil count (ANC) >= 1,000/mm^3

• Platelet count >= 100,000/mm^3

• Hemoglobin >= 8 g/dL

• Calculated (Calc.) creatinine clearance >= 30 mL/min using the Cockcroft-Gault equation

• Total serum bilirubin =< 1.5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN (or =< 5 x ULN for patients with liver metastases or Gilbert's disease)

• Urine protein creatinine (UPC) ratio =< 1 or 24-hour protein < 1 g

• Physicians should consider whether any of the following may render the patient inappropriate for this protocol:

  • Psychiatric illness which would prevent the patient from giving informed consent.
  • Uncontrolled medical conditions which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
  • Patients who cannot swallow oral formulations of the agent(s).

In addition:

• Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Include as applicable: Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom).
• Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and or steroids equivalent to < 10 mg prednisone daily, not on immunosuppressive medications and patients with positive serology are eligible. Patients with vitiligo, endocrine deficiencies including hypo or hyper thyroid disease managed with replacement, diabetes type 1 are eligible.
• Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the study and continue for 4 months after the last dose of study drugs, even if oral contraceptives are also used.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B (avelumab, cabozantinib)	Cabozantinib S-malate	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle and cabozantinib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm A (avelumab)	Avelumab	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm A (avelumab)	Biospecimen Collection	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm A (avelumab)	Bone Scan	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm A (avelumab)	Computed Tomography	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm A (avelumab)	Magnetic Resonance Imaging	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm A (avelumab)	Quality-of-Life Assessment	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm A (avelumab)	Questionnaire Administration	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm B (avelumab, cabozantinib)	Avelumab	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle and cabozantinib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm B (avelumab, cabozantinib)	Biospecimen Collection	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle and cabozantinib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm B (avelumab, cabozantinib)	Bone Scan	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle and cabozantinib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm B (avelumab, cabozantinib)	Computed Tomography	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle and cabozantinib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm B (avelumab, cabozantinib)	Magnetic Resonance Imaging	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle and cabozantinib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm B (avelumab, cabozantinib)	Quality-of-Life Assessment	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle and cabozantinib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
Arm B (avelumab, cabozantinib)	Questionnaire Administration	Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle and cabozantinib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.

Primary Outcome Measures

Name	Time	Method
Overall survival (OS)	Time from randomization until death due to any cause, assessed up to 5 years	Subgroup analyses will be done using a stratified Cox model that includes the treatment arm assignment as an explanatory variable and a separate model will be generated for each level for the subgroup of interest.

Secondary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	Time from randomization until disease progression as assessed by the treating physician using Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, assessed up to 5 years	A stratified Cox model will be used to compare the outcomes between the two treatment groups. The subgroup analyses will be done using a stratified Cox model that includes the treatment arm assignment as an explanatory variable and a separate model will be generated for each level for the subgroup of interest.
Tumor response	Up to 5 years	Will be defined as a complete response or partial response (PR) as measured with Immune-Modified RECIST. Will be compared between the arms using a Mantel-Haenszel test (that accounts for the randomization stratification factors) comparing the response rates between the two treatment arms. This analysis will only include patients who had a PR or stable disease (SD) response to first-line therapy. An additional analysis will be conducted using logistic regression analysis that includes treatment arm and any baseline variables that are imbalanced between the arms as explanatory variable.
Incidence of adverse events (AE)	Up to 5 years	Will be assessed by Common Terminology Criteria for Adverse Events 5.0. Will be summarized with frequencies and relative frequencies. The maximum grade for an AE will be recorded for each patient by treatment arm. The number (percent) of patients that experience each observed adverse event will be summarized by treatment arm. In addition, the proportion of patients that experience a grade 3+, grade 4+, and grade 5 adverse event will be summarized as the number and percent of patients by treatment arm. The primary summary will be regardless of attribution. Will also do an analogous summary for the adverse events that were deemed at least possibly related to treatment.

Trial Locations

Locations (276)

Mayo Clinic in Florida; 🇺🇸 Jacksonville, Florida, United States

Cleveland Clinic-Weston; 🇺🇸 Weston, Florida, United States

Rush - Copley Medical Center; 🇺🇸 Aurora, Illinois, United States

Advocate Good Shepherd Hospital; 🇺🇸 Barrington, Illinois, United States

Illinois CancerCare-Bloomington; 🇺🇸 Bloomington, Illinois, United States

Illinois CancerCare-Canton; 🇺🇸 Canton, Illinois, United States

Illinois CancerCare-Carthage; 🇺🇸 Carthage, Illinois, United States

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

Northwestern University; 🇺🇸 Chicago, Illinois, United States

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

Cross Cancer Institute; 🇨🇦 Edmonton, Alberta, Canada

University Health Network-Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

Allan Blair Cancer Centre; 🇨🇦 Regina, Saskatchewan, Canada

Saskatoon Cancer Centre; 🇨🇦 Saskatoon, Saskatchewan, Canada

University of Florida Health Science Center - Gainesville; 🇺🇸 Gainesville, Florida, United States

Mayo Clinic Hospital in Arizona; 🇺🇸 Phoenix, Arizona, United States

Sutter Auburn Faith Hospital; 🇺🇸 Auburn, California, United States

Alta Bates Summit Medical Center-Herrick Campus; 🇺🇸 Berkeley, California, United States

Palo Alto Medical Foundation-Fremont; 🇺🇸 Fremont, California, United States

Memorial Medical Center; 🇺🇸 Modesto, California, United States

Palo Alto Medical Foundation-Camino Division; 🇺🇸 Mountain View, California, United States

Palo Alto Medical Foundation Health Care; 🇺🇸 Palo Alto, California, United States

Sutter Roseville Medical Center; 🇺🇸 Roseville, California, United States

Sutter Medical Center Sacramento; 🇺🇸 Sacramento, California, United States

University of California Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

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

Palo Alto Medical Foundation-Santa Cruz; 🇺🇸 Santa Cruz, California, United States

Palo Alto Medical Foundation-Sunnyvale; 🇺🇸 Sunnyvale, California, United States

Sutter Solano Medical Center/Cancer Center; 🇺🇸 Vallejo, California, United States

Beebe South Coastal Health Campus; 🇺🇸 Millville, Delaware, United States

Helen F Graham Cancer Center; 🇺🇸 Newark, Delaware, United States

Medical Oncology Hematology Consultants PA; 🇺🇸 Newark, Delaware, United States

Beebe Health Campus; 🇺🇸 Rehoboth Beach, Delaware, United States

MedStar Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States

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

University of Illinois; 🇺🇸 Chicago, Illinois, United States

Advocate Illinois Masonic Medical Center; 🇺🇸 Chicago, Illinois, United States

AMG Crystal Lake - Oncology; 🇺🇸 Crystal Lake, Illinois, United States

Carle at The Riverfront; 🇺🇸 Danville, Illinois, United States

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

Northwestern Medicine Cancer Center Kishwaukee; 🇺🇸 DeKalb, Illinois, United States

Illinois CancerCare-Dixon; 🇺🇸 Dixon, Illinois, United States

Advocate Good Samaritan Hospital; 🇺🇸 Downers Grove, Illinois, United States

Carle Physician Group-Effingham; 🇺🇸 Effingham, Illinois, United States

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

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

Illinois CancerCare-Eureka; 🇺🇸 Eureka, Illinois, United States

Illinois CancerCare-Galesburg; 🇺🇸 Galesburg, Illinois, United States

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

Advocate South Suburban Hospital; 🇺🇸 Hazel Crest, Illinois, United States

Illinois CancerCare-Kewanee Clinic; 🇺🇸 Kewanee, Illinois, United States

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

AMG Libertyville - Oncology; 🇺🇸 Libertyville, Illinois, United States

Condell Memorial Hospital; 🇺🇸 Libertyville, Illinois, United States

Illinois CancerCare-Macomb; 🇺🇸 Macomb, Illinois, United States

Carle Physician Group-Mattoon/Charleston; 🇺🇸 Mattoon, Illinois, United States

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

Advocate Christ Medical Center; 🇺🇸 Oak Lawn, Illinois, United States

Illinois CancerCare-Ottawa Clinic; 🇺🇸 Ottawa, Illinois, United States

Advocate Lutheran General Hospital; 🇺🇸 Park Ridge, Illinois, United States

Illinois CancerCare-Pekin; 🇺🇸 Pekin, Illinois, United States

Illinois CancerCare-Peoria; 🇺🇸 Peoria, Illinois, United States

Illinois CancerCare-Peru; 🇺🇸 Peru, Illinois, United States

Illinois CancerCare-Princeton; 🇺🇸 Princeton, Illinois, United States

UW Health Carbone Cancer Center Rockford; 🇺🇸 Rockford, Illinois, United States

Memorial Hospital East; 🇺🇸 Shiloh, Illinois, United States

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

Springfield Clinic; 🇺🇸 Springfield, Illinois, United States

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

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

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

Illinois CancerCare - Washington; 🇺🇸 Washington, Illinois, United States

Rush-Copley Healthcare Center; 🇺🇸 Yorkville, Illinois, United States

Northwest Cancer Center - Main Campus; 🇺🇸 Crown Point, Indiana, United States

Northwest Oncology LLC; 🇺🇸 Dyer, Indiana, United States

Northwest Cancer Center - Hobart; 🇺🇸 Hobart, Indiana, United States

Saint Mary Medical Center; 🇺🇸 Hobart, Indiana, United States

Saint Catherine Hospital; 🇺🇸 Indianapolis, Indiana, United States

The Community Hospital; 🇺🇸 Munster, Indiana, United States

Women's Diagnostic Center - Munster; 🇺🇸 Munster, Indiana, United States

Northwest Cancer Center - Valparaiso; 🇺🇸 Valparaiso, Indiana, United States

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

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

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

McFarland Clinic - Trinity Cancer Center; 🇺🇸 Fort Dodge, Iowa, United States

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

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

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

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

Harold Alfond Center for Cancer Care; 🇺🇸 Augusta, Maine, United States

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States

UMass Memorial Medical Center - University Campus; 🇺🇸 Worcester, Massachusetts, United States

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

Bronson Battle Creek; 🇺🇸 Battle Creek, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Brighton; 🇺🇸 Brighton, Michigan, United States

Trinity Health Medical Center - Brighton; 🇺🇸 Brighton, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Canton; 🇺🇸 Canton, Michigan, United States

Trinity Health Medical Center - Canton; 🇺🇸 Canton, Michigan, United States

Chelsea Hospital; 🇺🇸 Chelsea, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital; 🇺🇸 Chelsea, Michigan, United States

Hematology Oncology Consultants-Clarkston; 🇺🇸 Clarkston, Michigan, United States

Newland Medical Associates-Clarkston; 🇺🇸 Clarkston, Michigan, United States

Cancer Hematology Centers - Flint; 🇺🇸 Flint, Michigan, United States

Genesee Hematology Oncology PC; 🇺🇸 Flint, Michigan, United States

Genesys Hurley Cancer Institute; 🇺🇸 Flint, Michigan, United States

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

Corewell Health Grand Rapids Hospitals - Butterworth Hospital; 🇺🇸 Grand Rapids, Michigan, United States

Trinity Health Grand Rapids Hospital; 🇺🇸 Grand Rapids, Michigan, United States

Bronson Methodist Hospital; 🇺🇸 Kalamazoo, Michigan, United States

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

Ascension Borgess Cancer Center; 🇺🇸 Kalamazoo, Michigan, United States

University of Michigan Health - Sparrow Lansing; 🇺🇸 Lansing, Michigan, United States

Trinity Health Saint Mary Mercy Livonia Hospital; 🇺🇸 Livonia, Michigan, United States

Henry Ford Saint John Hospital - Macomb Medical; 🇺🇸 Macomb, Michigan, United States

Trinity Health Muskegon Hospital; 🇺🇸 Muskegon, Michigan, United States

Cancer and Hematology Centers of Western Michigan - Norton Shores; 🇺🇸 Norton Shores, Michigan, United States

Hope Cancer Center; 🇺🇸 Pontiac, Michigan, United States

Michigan Healthcare Professionals Pontiac; 🇺🇸 Pontiac, Michigan, United States

Newland Medical Associates-Pontiac; 🇺🇸 Pontiac, Michigan, United States

Trinity Health Saint Joseph Mercy Oakland Hospital; 🇺🇸 Pontiac, Michigan, United States

Corewell Health Reed City Hospital; 🇺🇸 Reed City, Michigan, United States

Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center; 🇺🇸 Saint Joseph, Michigan, United States

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

University of Michigan Health - West; 🇺🇸 Wyoming, Michigan, United States

Huron Gastroenterology PC; 🇺🇸 Ypsilanti, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus; 🇺🇸 Ypsilanti, Michigan, United States

Sanford Joe Lueken Cancer Center; 🇺🇸 Bemidji, Minnesota, United States

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

Hennepin County Medical Center; 🇺🇸 Minneapolis, Minnesota, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, 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

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

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

Saint Francis Medical Center; 🇺🇸 Cape Girardeau, Missouri, United States

MU Health - University Hospital/Ellis Fischel Cancer Center; 🇺🇸 Columbia, Missouri, United States

Siteman Cancer Center at West County Hospital; 🇺🇸 Creve Coeur, Missouri, United States

Saint Luke's Hospital of Kansas City; 🇺🇸 Kansas City, Missouri, United States

Saint Luke's East - Lee's Summit; 🇺🇸 Lee's Summit, Missouri, United States

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

Siteman Cancer Center-South County; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center at Christian Hospital; 🇺🇸 Saint Louis, Missouri, United States

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

Siteman Cancer Center at Saint Peters Hospital; 🇺🇸 Saint Peters, Missouri, United States

OptumCare Cancer Care at Seven Hills; 🇺🇸 Henderson, Nevada, United States

OptumCare Cancer Care at Charleston; 🇺🇸 Las Vegas, Nevada, United States

OptumCare Cancer Care at Fort Apache; 🇺🇸 Las Vegas, Nevada, United States

New Hampshire Oncology Hematology PA-Concord; 🇺🇸 Concord, New Hampshire, United States

Solinsky Center for Cancer Care; 🇺🇸 Manchester, New Hampshire, United States

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

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

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

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

Morristown Medical Center; 🇺🇸 Morristown, New Jersey, United States

Saint Joseph's Regional Medical Center; 🇺🇸 Paterson, New Jersey, United States

Overlook Hospital; 🇺🇸 Summit, New Jersey, United States

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

Memorial Medical Center-Las Cruces; 🇺🇸 Las Cruces, New Mexico, United States

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

Arnot Ogden Medical Center/Falck Cancer Center; 🇺🇸 Elmira, New York, United States

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

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

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

Upstate Cancer Center at Oswego; 🇺🇸 Oswego, New York, United States

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

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

SUNY Upstate Medical Center-Community Campus; 🇺🇸 Syracuse, New York, United States

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

Upstate Cancer Center at Verona; 🇺🇸 Verona, New York, United States

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

Levine Cancer Institute-SouthPark; 🇺🇸 Charlotte, North Carolina, United States

Atrium Health University City/LCI-University; 🇺🇸 Charlotte, North Carolina, United States

Levine Cancer Institute-Ballantyne; 🇺🇸 Charlotte, North Carolina, United States

Southeastern Medical Oncology Center-Clinton; 🇺🇸 Clinton, North Carolina, United States

Atrium Health Cabarrus/LCI-Concord; 🇺🇸 Concord, North Carolina, United States

Southeastern Medical Oncology Center-Goldsboro; 🇺🇸 Goldsboro, North Carolina, United States

Southeastern Medical Oncology Center-Jacksonville; 🇺🇸 Jacksonville, North Carolina, United States

Atrium Health Lincoln/LCI-Lincolnton; 🇺🇸 Lincolnton, North Carolina, United States

Atrium Health Cleveland/LCI-Cleveland; 🇺🇸 Shelby, North Carolina, United States

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, 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

Cleveland Clinic Akron General; 🇺🇸 Akron, Ohio, United States

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

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

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

Premier Blood and Cancer Center; 🇺🇸 Dayton, Ohio, United States

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

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

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

Miami Valley Cancer Care and Infusion; 🇺🇸 Greenville, Ohio, United States

Kettering Medical Center; 🇺🇸 Kettering, Ohio, United States

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

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

North Coast Cancer Care; 🇺🇸 Sandusky, Ohio, United States

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

Toledo Clinic Cancer Centers-Toledo; 🇺🇸 Toledo, Ohio, United States

Upper Valley Medical Center; 🇺🇸 Troy, Ohio, United States

South Pointe Hospital; 🇺🇸 Warrensville Heights, Ohio, United States

Cleveland Clinic Wooster Family Health and Surgery Center; 🇺🇸 Wooster, Ohio, United States

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

Oklahoma Cancer Specialists and Research Institute-Tulsa; 🇺🇸 Tulsa, Oklahoma, United States

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

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

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

Lehigh Valley Hospital-Cedar Crest; 🇺🇸 Allentown, Pennsylvania, United States

Lehigh Valley Hospital - Muhlenberg; 🇺🇸 Bethlehem, Pennsylvania, United States

Penn State Health Medical Group - Andrews Patel Hematology/Oncology East; 🇺🇸 Harrisburg, Pennsylvania, United States

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

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

Jefferson Methodist Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Prisma Health Cancer Institute - Spartanburg; 🇺🇸 Boiling Springs, South Carolina, United States

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

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

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

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

Prisma Health Greenville Memorial Hospital; 🇺🇸 Greenville, South Carolina, United States

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

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

Levine Cancer Institute-Rock Hill; 🇺🇸 Rock Hill, South Carolina, United States

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

Avera Cancer Institute-Aberdeen; 🇺🇸 Aberdeen, South Dakota, 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

Aurora Cancer Care-Racine; 🇺🇸 Racine, Wisconsin, United States

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

Avera Cancer Institute at Yankton; 🇺🇸 Yankton, South Dakota, United States

University Cancer Specialists - Alcoa; 🇺🇸 Alcoa, Tennessee, United States

University of Tennessee - Knoxville; 🇺🇸 Knoxville, Tennessee, United States

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

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

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

UT Southwestern Clinical Center at Richardson/Plano; 🇺🇸 Richardson, Texas, United States

Bon Secours Memorial Regional Medical Center; 🇺🇸 Mechanicsville, Virginia, United States

Bon Secours Saint Francis Medical Center; 🇺🇸 Midlothian, Virginia, United States

Bon Secours Saint Mary's Hospital; 🇺🇸 Richmond, Virginia, United States

Virginia Cancer Institute; 🇺🇸 Richmond, Virginia, United States

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

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

VCU Community Memorial Health Center; 🇺🇸 South Hill, Virginia, United States

Shenandoah Oncology PC; 🇺🇸 Winchester, Virginia, United States

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

Valley Medical Center; 🇺🇸 Renton, Washington, United States

Vince Lombardi Cancer Clinic-Sheboygan; 🇺🇸 Sheboygan, Wisconsin, United States

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

Legacy Cancer Institute Medical Oncology and Day Treatment; 🇺🇸 Vancouver, Washington, United States

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

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

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

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

Aurora Health Care Germantown Health Center; 🇺🇸 Germantown, Wisconsin, United States

Aurora Cancer Care-Grafton; 🇺🇸 Grafton, Wisconsin, United States

Aurora BayCare Medical Center; 🇺🇸 Green Bay, Wisconsin, United States

Aurora Cancer Care-Kenosha South; 🇺🇸 Kenosha, Wisconsin, United States

Aurora Bay Area Medical Group-Marinette; 🇺🇸 Marinette, Wisconsin, United States

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

Froedtert Menomonee Falls Hospital; 🇺🇸 Menomonee Falls, Wisconsin, United States

Aurora Cancer Care-Milwaukee; 🇺🇸 Milwaukee, Wisconsin, United States

Aurora Saint Luke's Medical Center; 🇺🇸 Milwaukee, Wisconsin, United States

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

Aurora Sinai Medical Center; 🇺🇸 Milwaukee, Wisconsin, United States

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

ProHealth D N Greenwald Center; 🇺🇸 Mukwonago, Wisconsin, United States

Cancer Center of Western Wisconsin; 🇺🇸 New Richmond, Wisconsin, United States

Drexel Town Square Health Center; 🇺🇸 Oak Creek, Wisconsin, United States

ProHealth Oconomowoc Memorial Hospital; 🇺🇸 Oconomowoc, Wisconsin, United States

Vince Lombardi Cancer Clinic - Oshkosh; 🇺🇸 Oshkosh, Wisconsin, United States

Aurora Medical Center in Summit; 🇺🇸 Summit, Wisconsin, United States

Vince Lombardi Cancer Clinic-Two Rivers; 🇺🇸 Two Rivers, Wisconsin, United States

ProHealth Waukesha Memorial Hospital; 🇺🇸 Waukesha, Wisconsin, United States

UW Cancer Center at ProHealth Care; 🇺🇸 Waukesha, Wisconsin, United States

Aurora Cancer Care-Milwaukee West; 🇺🇸 Wauwatosa, Wisconsin, United States

Aurora West Allis Medical Center; 🇺🇸 West Allis, Wisconsin, United States

Froedtert West Bend Hospital/Kraemer Cancer Center; 🇺🇸 West Bend, Wisconsin, United States