New hope for cancer patients with autoimmune conditions: immune checkpoint inhibitor trial expands access
NCT ID NCT03816345
First seen Jun 27, 2026 · Last updated Sep 16, 2026 · Updated 3 times
Summary
This study is for people who have both an autoimmune disease (like rheumatoid arthritis, lupus, or multiple sclerosis) and an advanced cancer that has spread or cannot be removed by surgery. It tests the safety and effectiveness of the immunotherapy drug nivolumab, given alone or with other treatments like ipilimumab, cabozantinib, or chemotherapy. The goal is to see if these combinations can shrink tumors while managing side effects in this specific patient group. About 300 adults will take part.
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 1
The first testing in people. Mainly checks safety and dose, usually in a small group.
- Participants
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About 300 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Jul 2019
- Expected to finish
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Mar 2028
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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18 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: * Patients can have either histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, or have a malignancy for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting, as well as the neoadjuvant or perioperative setting in which such treatment is considered standard of care or has been approved. Eligible tumor types include solid tumors and malignancies in which there is known evidence of clinical activity for single agent PD-1 or PD-L1 antibodies. Nivolumab or other PD1/PD-L1 inhibitors are FDA-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible but must follow standard response criteria. Additional tumor types may be eligible on a case by case basis upon discussion with principal investigator (PI) * Patients enrolling on the trial for adjuvant use will be restricted to those with histology for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC, cervical cancer, and bladder cancer * Patients enrolled on the study can receive Nivolumab with other FDA-approved combinations according to the FDA package insert, including, but not limited to ipilimumab, cabozantinib or chemotherapy * Patients who have previously received other forms of immunotherapy (high-dose \[HD\] IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy for at least 4 weeks before nivolumab administration. Patients who have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks * Age \>= 18 years; children are excluded from this study but may be eligible for future pediatric phase 1 combination trials * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky \>= 60) * Life expectancy of greater than 12 weeks * Leukocytes \>= 1,000/mcL * Absolute neutrophil count \>= 500/mcL * Platelets \>= 50,000/mcL * Total bilirubin =\< 2 x institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN or =\< 8 x institutional ULN for patients with liver metastases or an autoimmune disease that is contributing to the elevation of these values * Creatinine ULN OR glomerular filtration rate (GFR) \>= 30 mL/min (if using the Cockcroft-Gault formula) * Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial * If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated * If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load * Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial * The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product * Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception * WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy), tubal ligation, or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL * These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days, and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days * Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately. Patients can resume treatment upon termination of a pregnancy or the completion of a successful pregnancy * Ability to understand and the willingness to sign a written informed consent document * Patients with more than one autoimmune disease are eligible. The treating physician would determine which autoimmune disease is dominant and the patient would be treated under that specific cohort (Please note: Patients with more than one autoimmune disease should receive assessments for all previously diagnosed autoimmune diseases. For example, a patient with psoriasis and IBD might be enrolled in the IBD cohort. Disease assessments for both psoriasis and IBD should be obtained, as per protocol. Case report forms \[CRFs\] for all relevant autoimmune diseases should be utilized. However, all additional cohort requirements will be considered optional and only the assessments from the assigned cohort will be considered mandatory) * DM/SSc-SPECIFIC INCLUSION: Patients with known SSc or DM according to updated classification criteria (Van den Hoogan et al., Arthritis Rheum 2013;65(11):2737-47; Lundberg et al., A\&R in press). Overlap features are permitted, but patients must meet criteria for a "primary diagnosis" of DM or SSc * DM/SSc-SPECIFIC INCLUSION: Patients may be on any concurrent therapy for DM or SSc unless specifically excluded * DM/SSc-SPECIFIC INCLUSION: Patients must have a baseline computed tomography (CT) of the chest (within 6 months of study entry) * RA-SPECIFIC INCLUSION: Rheumatologist-diagnosed RA requiring prior treatment with disease-modifying antirheumatic drugs (DMARDs) before patient was diagnosed with current malignancy. We recommend, but do not require, documentation for meeting 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA * RA-SPECIFIC INCLUSION: Prednisone up to 10 mg/day will be allowed. Intraarticular steroids will be allowed for the treatment of new symptomatic joints * RA-SPECIFIC INCLUSION: Nonsteroidal anti-inflammatory drugs (NSAIDs) will be allowed * SLE-SPECIFIC INCLUSION: SLE diagnosed by a rheumatologist. The patient should meet the revised 1997 American College of Rheumatology (ACR) classification criteria for SLE, but this is not mandatory * ULCERATIVE COLITIS (UC)-SPECIFIC INCLUSION: Diagnosis of UC must be made by endoscopy with biopsies * UC-SPECIFIC INCLUSION: Complete colonoscopy with biopsies during study screening, within 8 weeks before initial nivolumab administration, or within 4 weeks after initial nivolumab administration * UC-SPECIFIC INCLUSION: Patients must test negative for hepatitis B (antigen \[Ag\] negative, antibody \[core (c)Ab\] negative, antibody \[surface (s)Ab\] positive or negative) and Mycobacterium tuberculosis (purified-protein- derivative \[PPD\] or enzyme-linked immunospot assay \[ELISpot or T-spot\]) or be on appropriate anti-microbial treatment for these infections * UC-SPECIFIC INCLUSION: Mild Disease Cohort: Patients must be in clinical remission, defined as a Mayo Clinic score (MCS) of 2 or lower and no subscore higher than 1, and an endoscopic subscore of 0 or 1 either without medications, or treated with 5-ASA derivative, probiotic, or prior fecal transplant * UC-SPECIFIC INCLUSION: Moderate Disease Cohort: Patients must be in clinical remission, defined as a MCS of 2 or lower and no subscore higher than 1, and an endoscopic subscore of 0 or 1 on 6-mercaptopurine, azathioprine, methotrexate, or rectal hydrocortisone, budesonide, or one of these medications in combination with any of the medications listed in the Mild cohort * UC-SPECIFIC INCLUSION: Severe Disease Cohort (A or B): Patients must either be A) in clinical remission, defined as a MCS of 2 or lower and no subscore higher than 1, and an endoscopic subscore of 0 or 1 on a biologic therapy targeting tumor necrosis alpha (TNF-α) (infliximab, adalimumab, golimumab, or other approved agent in this class), α4β7 integrin (vedolizumab or other approved agent in this class), selective JAK1 inhibitor (upadacitinib or other approved agent in this class), IL-23p19 inhibitors (risankizumab or other approved agent in this class), selective sphingosine 1-phosphate receptor (S1PR) inhibitors (ozanimod, etrasimod or other approved agent in this class), or one of these biologic therapies in combination with any of the medications listed in the Mild or Moderate cohort, or B) have mild active disease defined as a MCS of 3-5 and no subscore higher than 2, and an endoscopic subscore of \< 2 on one of the medications or combination of medications defined for the Moderate or Mild cohort * CROHN'S DISEASE (CD)-SPECIFIC INCLUSION: Complete colonoscopy with biopsies during study screening, within 8 weeks before initial nivolumab administration, or within 4 weeks after initial nivolumab administration * CD-SPECIFIC INCLUSION: If patients have prior known disease in the stomach or small intestines, appropriate endoscopic evaluation (esophagogastroduodenoscopy/video capsule endoscopy) and/or imaging (computed tomography or magnetic resonance enterography) must also be current within 4 weeks prior to nivolumab administration * CD-SPECIFIC INCLUSION: Deep enteroscopy techniques, such as double balloon enteroscopy, will not be required * CD-SPECIFIC INCLUSION: Patients must test negative for hepatitis B (sAg negative, cAb negative, sAb positive or negative) and M. tuberculosis (PPD or ELISpot or T-spot) or be on appropriate anti-microbial treatment for these infections * CD-SPECIFIC INCLUSION: Mild Disease Cohort: Patients must be in clinical remission as defined by a Crohn's Disease Activity Index (CDAI) \< 150 either without treatment or on a 5-ASA derivative, probiotic, antibiotics, or following fecal transplant * CD-SPECIFIC INCLUSION: Moderate Disease Cohort: Patients must be in clinical remission as defined by a CDAI \< 150 on 6-mercaptopurine, azathioprine, methotrexate, rectal hydrocortisone, budesonide, or one of these medications in combination with any of the medications listed in the Mild cohort * CD-SPECIFIC INCLUSION: Severe Disease Cohort (A or B): Patients must either A) be in clinical remission as defined by a CDAI \< 150 on biologic therapy targeting TNF-α (infliximab, adalimumab, certolizumab pegol, or other approved agent in this class), IL-12/23p40 (Ustekinumab or other approved agent in this class), α4β7 integrin (vedolizumab or other approved agent in this class), selective JAK1 inhibitor (upadacitinib or other approved agent in this class), selective sphingosine 1-phosphate receptor (S1PR) inhibitors (ozanimod, etrasimod or other approved agent in this class), or one of these biologic therapies in combination with any of the medications listed in the Mild or Moderate cohort, or B) have mild active disease as defined by a CDAI of 150 to 220 on one of medications or combination of medications defined for the Moderate or Mild cohort * OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: For other autoimmune diseases that cannot be classified, the eligibility criteria will be determined by the managing rheumatologist or other autoimmune disease specialist, based on the clinical judgement and current American College of Radiology (ACR) classification guidelines or other relevant guidelines, as per the disease category in question * OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: For giant cell arteritis (GCA), patients must have had positive temporal artery biopsy for GCA and abnormal erythrocyte sedimentation rate (ESR) at time of diagnosis * OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: For polymyalgia rheumatica (PMR), patients must have clinical diagnosis in addition to elevated inflammatory markers including (ESR, C reactive protein \[CRP\]) * OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: Patients can be in remission (with no glucocorticoids or immunosuppressive medications) or have low-moderate activity, which is defined as being on prednisone ≤ 10 mg or equivalent * MS-SPECIFIC INCLUSION: Patients must meet 2017 McDonald criteria for the diagnosis of MS (Thompson AJ, et al. Diagnosis of multiple sclerosis: 2017 revision of the McDonald criteria. Lancet Neurol. 17(2):162-173.) * MS-SPECIFIC INCLUSION: Patients with MS can be in remission and can have a history of being on immunomodulatory agents, but at the time of entry into the clinical trial, patients should be off any concurrent MS therapy for at least 2 weeks. Patients can resume concurrent MS therapy 2 weeks after Nivolumab initiation. Patients in the MS2 cohort may be receiving contemporary multiple sclerosis disease modifying therapies, including but not limited to anti CD20 agents (ocrelizumab, rituximab, ofatumumab, ublituximab), sphingosine 1 phosphate (S1P) modulators (fingolimod, siponimod, ozanimod, ponesimod), cladribine, or other FDA approved MS therapies * MS-SPECIFIC INCLUSION: Patients must have neurologic stability for at least 4 weeks prior to nivolumab initiation * SJS-SPECIFIC INCLUSION: SjS diagnosed by a rheumatologist or oral medicine provider. The patient should meet the American-European Consensus Criteria for Sjögren's Syndrome (Vitali, et al., 2002). If on treatment, the patient may only be on hydroxychloroquine and prednisone ≤ 10 mg or equivalent * PSO/PSA-SPECIFIC INCLUSION: Patients with known PsO as diagnosed by a dermatologist or PsA by a rheumatologist and/or by Classification for Psoriatic Arthritis (CASPAR) criteria (Tillett et al., 2012) * PSO/PSA-SPECIFIC INCLUSION: Patients must have stable disease as determined by the investigator with no change in systemic therapy and/or biologic therapy for at least 3 months, except for those on tumor necrosis factor (TNF) inhibitors. In the case of TNF inhibition, patients may have transitioned to an alternative biologic therapy with stable disease for at least 4 weeks. For PsA, no change in corticosteroid therapy for at least 1 month prior to baseline and dose must be 10 mg or less * PSO/PSA-SPECIFIC INCLUSION: Patients may be on any concurrent therapy for PsO or PsA unless specifically excluded Exclusion Criteria: * Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier have not resolved or stabilized. Palliative (limited-field) radiation therapy (RT) is permitted (2 week washout from start of treatment), 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 * Patients with prior therapy with an anti-PD-1 or anti-PD-L1 * Patients with prior allogeneic hematologic transplant * Patients who are receiving any other anticancer investigational agents * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Patients with thymoma concurrent with myasthenia gravis * UC-SPECIFIC EXCLUSION: Patients who have received ipilimumab treatment * UC-SPECIFIC EXCLUSION: Prior colectomy * UC-SPECIFIC EXCLUSION: Concurrent primary sclerosing cholangitis (PSC). Patients with PSC can be enrolled on the Other Autoimmune Diseases Cohorts * UC-SPECIFIC EXCLUSION: Patients on empiric immunosuppressive treatment without any clinical workup * CD-SPECIFIC EXCLUSION: Known untreated abscesses, untreated and symptomatic strictures, short gut physiology, or isolated jejunal disease * CD-SPECIFIC EXCLUSION: Patients who have received ipilimumab treatment * CD-SPECIFIC EXCLUSION: Patients on empiric immunosuppressive treatment without any clinical workup * MS-SPECIFIC EXCLUSION: Patients with MS cannot have medical contraindications to gadolinium-enhanced magnetic resonance imaging (MRI)
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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
43 sites in 2 countries. 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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Dana-Farber Cancer Institute
RECRUITINGBoston, Massachusetts, 02215, United States
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Emory University Hospital/Winship Cancer Institute
ACTIVE_NOT_RECRUITINGAtlanta, Georgia, 30322, United States
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HaysMed
RECRUITINGHays, Kansas, 67601, United States
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Huntsman Cancer Institute/University of Utah
ACTIVE_NOT_RECRUITINGSalt Lake City, Utah, 84112, United States
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Johns Hopkins University/Sidney Kimmel Cancer Center
RECRUITINGBaltimore, Maryland, 21287, United States
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Laura and Isaac Perlmutter Cancer Center at NYU Langone
RECRUITINGNew York, New York, 10016, United States
Contact Email: •••••@•••••
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Lawrence Memorial Hospital
RECRUITINGLawrence, Kansas, 66044, United States
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Massachusetts General Hospital Cancer Center
RECRUITINGBoston, Massachusetts, 02114, United States
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MedStar Georgetown University Hospital
RECRUITINGWashington D.C., District of Columbia, 20007, United States
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Mercy Hospital Pittsburg
SUSPENDEDPittsburg, Kansas, 66762, United States
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NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
RECRUITINGNew York, New York, 10032, United States
Contact Email: •••••@•••••
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NYP/Weill Cornell Medical Center
RECRUITINGNew York, New York, 10065, United States
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NYU Langone Hospital - Long Island
RECRUITINGMineola, New York, 11501, United States
Contact Email: •••••@•••••
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National Cancer Institute Developmental Therapeutics Clinic
RECRUITINGBethesda, Maryland, 20892, United States
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National Institutes of Health Clinical Center
ACTIVE_NOT_RECRUITINGBethesda, Maryland, 20892, United States
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Northwestern University
ACTIVE_NOT_RECRUITINGChicago, Illinois, 60611, United States
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Ohio State University Comprehensive Cancer Center
RECRUITINGColumbus, Ohio, 43210, United States
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Rutgers Cancer Institute of New Jersey
RECRUITINGNew Brunswick, New Jersey, 08903, United States
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Salina Regional Health Center
RECRUITINGSalina, Kansas, 67401, United States
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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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Smilow Cancer Center/Yale-New Haven Hospital
RECRUITINGNew Haven, Connecticut, 06510, United States
Contact Email: •••••@•••••
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Stanford Cancer Institute Palo Alto
ACTIVE_NOT_RECRUITINGPalo Alto, California, 94304, United States
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The University of Kansas Cancer Center - Olathe
RECRUITINGOlathe, Kansas, 66061, United States
Contact Email: •••••@•••••
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Thomas Jefferson University Hospital
ACTIVE_NOT_RECRUITINGPhiladelphia, Pennsylvania, 19107, United States
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UPMC Hillman Cancer Center
RECRUITINGPittsburgh, Pennsylvania, 15232, United States
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UT MD Anderson Cancer Center
RECRUITINGHouston, Texas, 77030, United States
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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 Health Network-Princess Margaret Hospital
SUSPENDEDToronto, Ontario, M5G 2M9, Canada
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University Health Truman Medical Center
RECRUITINGKansas City, Missouri, 64108, United States
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University of Alabama at Birmingham Cancer Center
ACTIVE_NOT_RECRUITINGBirmingham, Alabama, 35233, United States
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University of California Davis Comprehensive Cancer Center
RECRUITINGSacramento, California, 95817, United States
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University of Chicago Comprehensive Cancer Center
ACTIVE_NOT_RECRUITINGChicago, Illinois, 60637, United States
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University of Kansas Cancer Center
RECRUITINGKansas City, Kansas, 66160, United States
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University of Kansas Cancer Center - Lee's Summit
RECRUITINGLee's Summit, Missouri, 64064, United States
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University of Kansas Cancer Center - North
RECRUITINGKansas City, Missouri, 64154, United States
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University of Kansas Cancer Center at North Kansas City Hospital
RECRUITINGNorth Kansas City, Missouri, 64116, United States
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University of Kansas Cancer Center-Overland Park
RECRUITINGOverland Park, Kansas, 66210, United States
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University of Kansas Clinical Research Center
RECRUITINGFairway, Kansas, 66205, United States
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University of Kansas Health System Saint Francis Campus
RECRUITINGTopeka, Kansas, 66606, United States
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University of Kansas Hospital-Indian Creek Campus
RECRUITINGOverland Park, Kansas, 66211, United States
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University of Kansas Hospital-Westwood Cancer Center
RECRUITINGWestwood, Kansas, 66205, United States
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University of Kentucky/Markey Cancer Center
RECRUITINGLexington, Kentucky, 40536, United States
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VCU Massey Comprehensive Cancer Center
RECRUITINGRichmond, Virginia, 23298, United States
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Washington University School of Medicine
RECRUITINGSt Louis, Missouri, 63110, United States
Contact Email: •••••@•••••
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Wayne State University/Karmanos Cancer Institute
ACTIVE_NOT_RECRUITINGDetroit, Michigan, 48201, United States
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Yale University
RECRUITINGNew Haven, Connecticut, 06520, United States
Contact Email: •••••@•••••
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