New drug cocktail takes on rare adrenal cancer
NCT ID NCT06900595
First seen Jun 25, 2026 · Last updated Sep 18, 2026 · Updated 16 times
Summary
This phase II trial tests whether adding the immunotherapy cemiplimab to the targeted drug cabozantinib works better than cabozantinib alone for advanced adrenocortical cancer. About 48 adolescents and adults whose cancer has spread or cannot be removed will take part. The study aims to see if the combination can delay cancer growth.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- cabozantinib and cemiplimab
- What this could lead to
- If successful, this combination could offer a new treatment option to slow or shrink advanced adrenocortical cancer when other therapies have failed.
- What could go wrong
- This is a small phase II trial, so results may not confirm benefit. The drugs can cause side effects like fatigue, high blood pressure, and immune-related reactions.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 2
Tests whether the treatment actually works, and watches for side effects, in a larger group.
- Participants
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About 48 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Feb 2026
- Expected to finish
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Jun 2029
An estimate. End dates often move.
- Lead sponsor
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A government research agency
The lead sponsor is the US National Institutes of Health.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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12 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * STEP 1: Patients must have documented histologically or cytologically confirmed adrenocortical carcinoma * STEP 1: Locally advanced unresectable or recurrent/metastatic disease * STEP 1: Evaluable disease as defined by RECIST v 1.1 * STEP 1: Up to 3 prior lines of systemic therapy will be allowed in the unresectable/recurrent/metastatic setting. Treatment naïve patients will be allowed. * Note: Combination etoposide, doxorubicin, cisplatin, and mitotane (EDP-M) is considered 1 line of therapy. For patients who received mitotane ≤ 6 months prior to registration, mitotane should be discontinued 28 days prior to study registration AND a mitotane level must be documented to be \< 2 mg/L prior to registration. Patients who have received mitotane within 6 months of enrollment and who have mitotane levels ≥ 2 mg/L will not be eligible to enroll * STEP 1: No prior treatment with cabozantinib or other cMET inhibitors, or anti-CTLA-4, or anti-PD-1/PD-L1 therapy * STEP 1: Prior external beam radiation therapy (any area radiated within a month prior to study registration cannot be used as an index lesion and only growth outside of the radiation field can be considered for disease progression), systemic cytotoxic chemotherapy, targeted therapies will be allowed, as long as not administered within 14 days before study registration, and provided any acute treatment-related associated toxicities have recovered to ≤ grade 1 except for alopecia, peripheral neuropathy or other residual toxicities that are not deemed clinically significant * STEP 1: Potential trial participants should have recovered from clinically significant adverse events, and wound healing is clinically adequate of their most recent therapy/intervention prior to enrollment * STEP 1: Age 12 years and above; and BSA ≥ 1.2m\^2 * STEP 1: * Eastern Cooperative Oncology Group (ECOG) performance 0 - 2 (age 18 and above); or * Patients 12 to \<16 years of age will be assessed by the Lansky scale and should have a score ≥ 50; or * Patients ≥ 16 to \<18 years of age will be assessed by the Karnofsky scale, and should have a score ≥ 50 * STEP 1: Absolute neutrophil count (ANC) ≥ 1,000/mcL without colony stimulating factor support within 2 weeks prior * Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory * STEP 1: Platelet count ≥ 100,000/mcL * Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory * STEP 1: Hemoglobin ≥ 8 g/dL * Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory * STEP 1: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) * For patients with known Gilbert's disease, bilirubin ≤ 3 mg/dL * STEP 1: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x upper limit of normal (ULN) * STEP 1: Random Urine Creatinine Ratio (UPCR) ≤ 1 mg/mg * STEP 1: Calculated (Calc.) creatinine clearance ≥ 30 mL/min * STEP 1: Mitotane level \< 2 mg/L\* * Only applicable for patients who have received mitotane ≤ 6 months prior to registration * STEP 1: Must have assessment of adrenal steroid production within 3 months prior to registration as patients will be stratified based on corticosteroid production * Patients will be classified as corticosteroid producing if random plasma adrenocorticotropic hormone (ACTH) is \< 20 pg/mL plus random serum cortisol is \> 20 mcg/dL in the absence of anti-cortisol therapy. Patients already on anti-cortisol therapy will be classified as having corticosteroid producing tumors regardless of their plasma ACTH and serum cortisol levels, as these levels can be affected by anti-cortisol therapy * STEP 1: Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects based on animal reproduction studies. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test, per institution standard, done ≤ 14 days prior to registration is required * STEP 1: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional within 28 days of registration. To be eligible for this trial, patients should be class II or better * STEP 1: No known history of congenital long QT syndrome * STEP 1: No known history of myocarditis * STEP 1: No myocardial infarction (MI) or unstable angina within 6 months of registration * STEP 1: No clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding within 6 months of registration including, but not limited to: active peptic ulcer, known endoluminal metastatic lesion(s) with history of bleeding, inflammatory bowel disease, or other gastrointestinal conditions with increased risk of perforation * STEP 1: No history of gastrointestinal (GI) perforation within 6 months of registration * STEP 1: No known tumor with invasion into the GI tract from the outside causing increased risk of perforation or bleeding within 28 days of registration * STEP 1: No current radiologic or clinical evidence of pancreatitis * STEP 1: No history of clinically significant non-healing wounds or ulcers within 28 days of registration * STEP 1: No uncontrolled hypertension within 14 days of registration (defined as sustained systolic blood pressure (SBP) ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg despite optimal medical management) * STEP 1: No known endobronchial lesions involving the main or lobar bronchi and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage. (CT with contrast is recommended to evaluate such lesions.). No hemoptysis greater than ½ teaspoon (2.5 mL) or any other signs of pulmonary hemorrhage within the 3 months prior to registration * STEP 1: No history of pneumonitis * STEP 1: No known tumor invading or encasing any major blood vessels * STEP 1: No history of fracture within 28 days of registration * STEP 1: No known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks after major surgery (e.g., removal or biopsy of brain metastasis) before registration. Eligible patients must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment * STEP 1: Major surgery (e.g., laparoscopic nephrectomy, GI surgery, within 2 weeks before registration. Minor surgeries within 10 days before registration. Patients with clinically relevant ongoing complications from prior surgery are not eligible * STEP 1: Verbalizes the ability to swallow oral tablet formulation * STEP 1: No history of allergic reaction attributed to compounds of similar chemical or biological composition to cabozantinib * STEP 1: 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 will be eligible * STEP 1: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial * STEP 1: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * STEP 1: 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 * STEP 1: 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 systemic lupus erythematosus (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, * Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible, * Patients with rheumatoid arthritis and other arthropathies, Sjögren'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 * STEP 1: No steroid use \> 10 mg prednisone equivalents daily. A brief course of corticosteroids for prophylaxis or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as is steroid pre-medication for contrast allergy * STEP 1: Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study * STEP 1: Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment * STEP 1: Herbal supplements and traditional Chinese medicines are not allowed * STEP 1: Active treatment with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct Xa inhibitor betrixaban or platelet inhibitors (e.g., clopidogrel) within 5 days of registration. Allowed use of anticoagulants include: 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, apixaban. Also use of anticoagulants is allowed in patients with known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor * STEP 2 (CROSSOVER): Patients must have demonstrated radiographic progression of disease on cabozantinib monotherapy (Arm A) per RECIST version 1.1 criteria * Patients must cross-over to Arm C within 4 weeks (+/- 1 week) after radiographic documented progression and do not need to have a repeat radiographic assessment prior to starting cabozantinib and cemiplimab (REGN2810). The progression CT may serve as eligibility for crossover and as the baseline tumor measurement * STEP 2 (CROSSOVER): Patients that were discontinued on cabozantinib, or currently meet criteria for discontinuation of cabozantinib due to toxicity are not eligible to cross-over. * Note: Patients who underwent dose reduction of cabozantinib during treatment on Arm A will not re-escalate dose at or after cross-over to Cabo-Cemiplimab (REGN2810) (Arm B) * STEP 2 (CROSSOVER): Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done ≤ 14 days prior to re-registration is required
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Get notified about this study
Sign up to get updates when this study changes or when new studies for Locally advanced adrenal cortical carcinoma are added.
Genom att skicka in godkänner du våra Användarvillkor
Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The study's own enquiry address
This study publishes an address for enquiries. See it below .
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The places running it
81 sites. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Show contact details
Enter your email to view the contact information for this study.
Genom att skicka in godkänner du våra Användarvillkor
Locations
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BI-LO Charities Children's Cancer Center
RECRUITINGGreenville, South Carolina, 29605, United States
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Broadlawns Medical Center
RECRUITINGDes Moines, Iowa, 50314, United States
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Carle BroMenn Medical Center
RECRUITINGNormal, Illinois, 61761, United States
Contact Email: •••••@•••••
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Carle Cancer Center
RECRUITINGUrbana, Illinois, 61801, United States
Contact Email: •••••@•••••
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Carle Cancer Institute Normal
RECRUITINGNormal, Illinois, 61761, United States
Contact Email: •••••@•••••
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Carle Physician Group-Effingham
RECRUITINGEffingham, Illinois, 62401, United States
Contact Email: •••••@•••••
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Carle Physician Group-Mattoon/Charleston
RECRUITINGMattoon, Illinois, 61938, United States
Contact Email: •••••@•••••
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Carle at The Riverfront
RECRUITINGDanville, Illinois, 61832, United States
Contact Email: •••••@•••••
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Children's Hospital of Pittsburgh of UPMC
RECRUITINGPittsburgh, Pennsylvania, 15224, United States
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Children's Hospital of San Antonio
RECRUITINGSan Antonio, Texas, 78207, United States
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Children's Mercy Hospitals and Clinics
RECRUITINGKansas City, Missouri, 64108, United States
Contact Email: •••••@•••••
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Cook Children's Medical Center
RECRUITINGFort Worth, Texas, 76104, United States
Contact Email: •••••@•••••
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CoxHealth South Hospital
RECRUITINGSpringfield, Missouri, 65807, United States
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Dana-Farber Cancer Institute
RECRUITINGBoston, Massachusetts, 02215, United States
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Dell Children's Medical Center of Central Texas
RECRUITINGAustin, Texas, 78723, United States
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Duke Cancer Center Cary
RECRUITINGCary, North Carolina, 27518, United States
Contact Email: •••••@•••••
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Duke Cancer Center Raleigh
RECRUITINGRaleigh, North Carolina, 27609, United States
Contact Email: •••••@•••••
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Duke University Medical Center
RECRUITINGDurham, North Carolina, 27710, United States
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Fred Hutchinson Cancer Center
RECRUITINGSeattle, Washington, 98109, United States
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Iowa Methodist Medical Center
RECRUITINGDes Moines, Iowa, 50309, United States
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Lurie Children's Hospital-Chicago
RECRUITINGChicago, Illinois, 60611, United States
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Mayo Clinic Hospital in Arizona
RECRUITINGPhoenix, Arizona, 85054, United States
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Mayo Clinic in Florida
RECRUITINGJacksonville, Florida, 32224-9980, United States
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Mayo Clinic in Rochester
RECRUITINGRochester, Minnesota, 55905, United States
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Memorial Hospital East
RECRUITINGShiloh, Illinois, 62269, United States
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Memorial Sloan Kettering Basking Ridge
RECRUITINGBasking Ridge, New Jersey, 07920, United States
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Memorial Sloan Kettering Bergen
RECRUITINGMontvale, New Jersey, 07645, United States
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Memorial Sloan Kettering Cancer Center
RECRUITINGNew York, New York, 10065, United States
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Memorial Sloan Kettering Commack
RECRUITINGCommack, New York, 11725, United States
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Memorial Sloan Kettering Monmouth
RECRUITINGMiddletown, New Jersey, 07748, United States
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Memorial Sloan Kettering Nassau
RECRUITINGUniondale, New York, 11553, United States
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Memorial Sloan Kettering Westchester
RECRUITINGHarrison, New York, 10604, United States
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Mercy Medical Center - Des Moines
RECRUITINGDes Moines, Iowa, 50314, United States
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Nebraska Medicine-Bellevue
RECRUITINGBellevue, Nebraska, 68123, United States
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Nebraska Medicine-Village Pointe
RECRUITINGOmaha, Nebraska, 68118, United States
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Northwestern Medicine Cancer Center Delnor
RECRUITINGGeneva, Illinois, 60134, United States
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Northwestern Medicine Cancer Center Kishwaukee
RECRUITINGDeKalb, Illinois, 60115, United States
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Northwestern Medicine Cancer Center Warrenville
RECRUITINGWarrenville, Illinois, 60555, United States
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Northwestern Medicine Glenview Outpatient Center
RECRUITINGGlenview, Illinois, 60026, United States
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Northwestern Medicine Grayslake Outpatient Center
RECRUITINGGrayslake, Illinois, 60030, United States
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Northwestern Medicine Lake Forest Hospital
RECRUITINGLake Forest, Illinois, 60045, United States
Contact Email: •••••@•••••
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Northwestern Medicine Oak Brook
RECRUITINGOak Brook, Illinois, 60523, United States
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Northwestern Medicine Orland Park
RECRUITINGOrland Park, Illinois, 60462, United States
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Northwestern University
RECRUITINGChicago, Illinois, 60611, United States
Contact Email: •••••@•••••
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Ohio State University Comprehensive Cancer Center
RECRUITINGColumbus, Ohio, 43210, United States
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Parkland Memorial Hospital
RECRUITINGDallas, Texas, 75235, United States
Contact Email: •••••@•••••
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Prisma Health Cancer Institute - Butternut
RECRUITINGGreenville, South Carolina, 29605, United States
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Prisma Health Cancer Institute - Easley
RECRUITINGEasley, South Carolina, 29640, United States
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Prisma Health Cancer Institute - Eastside
RECRUITINGGreenville, South Carolina, 29615, United States
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Prisma Health Cancer Institute - Faris
RECRUITINGGreenville, South Carolina, 29605, United States
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Prisma Health Cancer Institute - Greer
RECRUITINGGreer, South Carolina, 29650, United States
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Prisma Health Cancer Institute - Seneca
RECRUITINGSeneca, South Carolina, 29672, United States
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Prisma Health Cancer Institute - Spartanburg
RECRUITINGBoiling Springs, South Carolina, 29316, United States
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Prisma Health Richland Hospital
RECRUITINGColumbia, South Carolina, 29203, United States
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Saint Anthony Regional Hospital
RECRUITINGCarroll, Iowa, 51401, United States
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Saint Jude Children's Research Hospital
RECRUITINGMemphis, Tennessee, 38105, United States
Contact Email: •••••@•••••
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Siteman Cancer Center at Christian Hospital
RECRUITINGSt Louis, Missouri, 63136, United States
Contact Email: •••••@•••••
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Siteman Cancer Center at Saint Peters Hospital
RECRUITINGCity of Saint Peters, Missouri, 63376, United States
Contact Email: •••••@•••••
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Siteman Cancer Center at West County Hospital
RECRUITINGCreve Coeur, Missouri, 63141, United States
Contact Email: •••••@•••••
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Siteman Cancer Center-South County
RECRUITINGSt Louis, Missouri, 63129, United States
Contact Email: •••••@•••••
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UC San Diego Moores Cancer Center
RECRUITINGLa Jolla, California, 92093, United States
Contact Email: •••••@•••••
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UCHealth University of Colorado Hospital
RECRUITINGAurora, Colorado, 80045, United States
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UI Health Care Mission Cancer and Blood - Ankeny Clinic
RECRUITINGAnkeny, Iowa, 50023, United States
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UI Health Care Mission Cancer and Blood - Des Moines Clinic
RECRUITINGDes Moines, Iowa, 50309, United States
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UI Health Care Mission Cancer and Blood - Laurel Clinic
RECRUITINGDes Moines, Iowa, 50314, United States
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UI Health Care Mission Cancer and Blood - Waukee Clinic
RECRUITINGWaukee, Iowa, 50263, United States
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UI Health Care Mission Cancer and Blood - West Des Moines Clinic
RECRUITINGClive, Iowa, 50325, United States
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UI Healthcare Mission Cancer and Blood - Fort Dodge
RECRUITINGFort Dodge, Iowa, 50501, United States
Contact Email: •••••@•••••
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UT Southwestern Clinical Center at Richardson/Plano
RECRUITINGRichardson, Texas, 75080, United States
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UT Southwestern Simmons Cancer Center - RedBird
RECRUITINGDallas, Texas, 75237, United States
Contact Email: •••••@•••••
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UT Southwestern/Simmons Cancer Center-Dallas
RECRUITINGDallas, Texas, 75390, United States
Contact Email: •••••@•••••
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UT Southwestern/Simmons Cancer Center-Fort Worth
RECRUITINGFort Worth, Texas, 76104, United States
Contact Email: •••••@•••••
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University of Michigan Rogel Cancer Center
RECRUITINGAnn Arbor, Michigan, 48109, United States
Contact Email: •••••@•••••
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University of Nebraska Medical Center
RECRUITINGOmaha, Nebraska, 68198, United States
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University of Oklahoma Health Sciences Center
RECRUITINGOklahoma City, Oklahoma, 73104, United States
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University of Texas Health Science Center at San Antonio
RECRUITINGSan Antonio, Texas, 78229, United States
Contact Email: •••••@•••••
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University of Washington Medical Center - Montlake
RECRUITINGSeattle, Washington, 98195, United States
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VCU Massey Cancer Center at Stony Point
RECRUITINGRichmond, Virginia, 23235, United States
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VCU Massey Comprehensive Cancer Center
RECRUITINGRichmond, Virginia, 23298, United States
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Valley Children's Hospital
RECRUITINGMadera, California, 93636, United States
Contact Email: •••••@•••••
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Washington University School of Medicine
RECRUITINGSt Louis, Missouri, 63110, United States
Contact Email: •••••@•••••
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