Autoimmune DiseasePhase 1NCT03816345
Testing an Immunotherapy Anti-cancer Drug, Nivolumab, for Advanced Cancers in Patients With Autoimmune Disorders, AIM-NIVO
A Phase 1 study testing Biospecimen Collection, Cabozantinib and Fluoropyrimidine in people with Autoimmune Disease and Crohn Disease, run by National Cancer Institute (NCI) at 52 sites in 2 countries.
Trial summary
This phase Ib trial studies the side effects of nivolumab and to see how well it works alone and in combination with other treatments, such as ipilimumab, cabozantinib, platinum containing therapy, and fluoropyrimidine, in treating patients with autoimmune disorders and cancer that has spread from where it first… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autoimmune Disease, Crohn Disease, Dermatomyositis
- What is being tested?
- Biospecimen Collection, Cabozantinib and Fluoropyrimidine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 52 sitesin 2 countries
- Study dates
- 16 Jul 2019to 30 Mar 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
52 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
52 sites in 2 countries
United States51 sites, 40 recruiting
- Active, not recruiting
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
- Recruiting
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Site Public Contact, 410-955-8804, jhcccro@jhmi.edu
Julie R. Brahmer
- Recruiting
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892
Site Public Contact, 800-411-1222
A P. Chen
- Active, not recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
- Active, not recruiting
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
- Recruiting
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Site Public Contact, 877-726-5130
Patrick A. Ott
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Site Public Contact, 877-442-3324
Patrick A. Ott
- Active, not recruiting
Northwestern University
Chicago, Illinois, 60611
- Active, not recruiting
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
- Recruiting
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Tanner M. Johanns
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Site Public Contact, 800-293-5066, Jamesline@osumc.edu
Yuanquan Yang
- Recruiting
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Tanner M. Johanns
- Recruiting
UT Southwestern Simmons Cancer Center - RedBird
Dallas, Texas, 75237
Site Public Contact, 214-648-7097, canceranswerline@utsouthwestern.edu
Hans Hammers
- Recruiting
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Site Public Contact, 214-648-7097, canceranswerline@UTSouthwestern.edu
Hans Hammers
- Active, not recruiting
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
- Recruiting
University of Kansas Clinical Research Center
Fairway, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Joaquina C. Baranda
- Recruiting
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth, Texas, 76104
Site Public Contact, 214-648-7097, canceranswerline@UTSouthwestern.edu
Hans Hammers
- Recruiting
HaysMed
Hays, Kansas, 67601
Site Public Contact, 785-623-5774
Joaquina C. Baranda
- Recruiting
UT MD Anderson Cancer Center
Houston, Texas, 77030
Site Public Contact, 866-632-6789, askmdanderson@mdanderson.org
Ecaterina E. Ileana Dumbrava
- Recruiting
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Joaquina C. Baranda
- Recruiting
University Health Truman Medical Center
Kansas City, Missouri, 64108
Site Public Contact, 816-404-4375
Joaquina C. Baranda
- Recruiting
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Joaquina C. Baranda
- Recruiting
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
Site Public Contact, 785-505-2800, Stephanie.Norris@LMH.ORG
Joaquina C. Baranda
- Recruiting
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Joaquina C. Baranda
- Recruiting
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Site Public Contact, 859-257-3379
Susanne M. Arnold
- Recruiting
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Site Public Contact, 212-263-4432, cancertrials@nyulangone.org
Janice M. Mehnert
- Recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Site Public Contact, 732-235-7356
Sarah A. Weiss
- Recruiting
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Patricia M. LoRusso
- Recruiting
Yale University
New Haven, Connecticut, 06520
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Patricia M. LoRusso
- Recruiting
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Site Public Contact, CancerTrials@nyulangone.org
Janice M. Mehnert
- Recruiting
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Site Public Contact, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
Brian S. Henick
- Recruiting
NYP/Weill Cornell Medical Center
New York, New York, 10065
Site Public Contact, 212-746-1848
Ashish Saxena
- Suspended
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116
- Recruiting
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, 66061
Site Public Contact, 913-588-1569, OlatheCCResearch@kumc.edu
Joaquina C. Baranda
- Recruiting
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Joaquina C. Baranda
- Recruiting
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Joaquina C. Baranda
- Active, not recruiting
Stanford Cancer Institute Palo Alto
Palo Alto, California, 94304
- Active, not recruiting
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
- Suspended
Mercy Hospital Pittsburg
Pittsburg, Kansas, 66762
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Site Public Contact, 412-647-8073
Yana Najjar
- Recruiting
UT Southwestern Clinical Center at Richardson/Plano
Richardson, Texas, 75080
Site Public Contact, 972-669-7044, Suzanne.cole@utsouthwestern.edu
Hans Hammers
- Recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Site Public Contact, 804-628-6430, CTOclinops@vcu.edu
Andrew Poklepovic
- Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Site Public Contact, 916-734-3089
Surbhi Singhal
- Recruiting
Salina Regional Health Center
Salina, Kansas, 67401
Site Public Contact, 785-452-7038, mleepers@srhc.com
Joaquina C. Baranda
- Active, not recruiting
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Tanner M. Johanns
- Recruiting
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Tanner M. Johanns
- Recruiting
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Tanner M. Johanns
- Recruiting
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606
Site Public Contact, 785-295-8000
Joaquina C. Baranda
- Recruiting
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Site Public Contact, 202-444-2223
Geoffrey T. Gibney
- Recruiting
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Joaquina C. Baranda
Canada1 site
- Suspended
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase Ib Study of Nivolumab in Patients With Autoimmune Disorders and Advanced Malignancies (AIM-NIVO)
This phase Ib trial studies the side effects of nivolumab and to see how well it works alone and in combination with other treatments, such as ipilimumab, cabozantinib, platinum containing therapy, and fluoropyrimidine, in treating patients with autoimmune disorders and cancer that has spread from where it first started (primary site) to nearby tissue, lymph nodes, or distant parts of the body (advanced), to other places in the body (metastatic) or cannot removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib blocks certain proteins, which may help keep tumor cells from growing. It may also prevent the growth of new blood vessels that tumors need to grow. Cabozantinib is a type of tyrosine kinase inhibitor and a type of angiogenesis inhibitor. Chemotherapy drugs, such as platinum containing therapies and fluoropyrimidine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab alone and in combination with other treatments, including ipilimumab, cabozantinib, platinum containing therapy, or fluoropyrimidine, may be safe, tolerable, and/or effective in treating patients with autoimmune disorders and advanced, metastatic, or unresectable cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the overall safety, and toxicities associated with the use of the anti-programmed death 1 (PD-1) antibody nivolumab in patients with varying severity of dermatomyositis (DM)/systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) (ulcerative colitis [UC] and Crohn's disease [CD]), multiple sclerosis (MS), Sjogren's syndrome [SjS], psoriasis (PsO)/psoriatic arthritis (PsA), and other autoimmune diseases.
II. To assess the overall safety, and toxicities associated with the use of the anti-programmed death 1 (PD-1) antibody nivolumab and other Food and Drug Administration (FDA)-approved combinations for given oncologic indications in patients with varying severity of DM/SSc, RA, SLE, IBD (ulcerative colitis [UC] and Crohn's disease [CD]), MS, Sjogren's syndrome [SjS], psoriasis (PsO)/psoriatic arthritis (PsA), and other autoimmune diseases.
SECONDARY OBJECTIVES:
- To evaluate the efficacy of nivolumab in terms of objective response rates (ORRs), progression-free survival (PFS), and overall survival (OS) in patients with cancer and DM/SSc, RA, SLE, IBD (UC and CD), MS, SjS, PsO/PsA, and other autoimmune diseases.
II. To observe and record anti-tumor activity. III. To propose dosing recommendations for anti-PD-1 antibodies based on the severity of the autoimmune disorder.
IV. To evaluate the impact of nivolumab on the disease severity indices for: DM/SSc, RA, SLE, IBD: UC and CD, not specified (NS), MS, SjS, PsO/PsA.
- To identify biomarkers of response and toxicity.
OUTLINE: Patients are assigned to 1 of 11 arms.
ARM I (MONOTHERAPY): Patients may receive single agent nivolumab intravenously (IV) over 30 minutes every 4 weeks for up to 2 years for patients with metastatic indications, for up to 1 year for adjuvant indications or for up to 3 months after surgery for neoadjuvant indications in the absence of disease progression or unacceptable toxicity.
ARM II (UNRESECTABLE OR METASTATIC MELANOMA): Patients receive nivolumab IV over 30 minutes every 2 or 4 weeks in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab may continue every 4 weeks in the absence of disease progression or unacceptable toxicity.
ARM III (NEOADJUVANT TREATMENT OF RESECTABLE NON-SMALL CELL LUNG CANCER [NSCLC]): Patients receive nivolumab IV over 30 minutes in combination with platinum doublet therapy every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
ARM IV (METASTATIC PD-L1 POSITIVE NSCLC): Patients receive nivolumab IV over 30 minutes every 3 weeks and ipilimumab IV every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM V (METASTATIC OR RECURRENT NSCLC): Patients receive nivolumab IV over 30 minutes every 3 weeks, ipilimumab IV every 6 weeks and platinum doublet therapy every 3 weeks for up to 2 cycles of combination therapy. Treatment with nivolumab and ipilimumab repeats for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM VI (MALIGNANT PLEURAL MESOTHELIOMA): Patients receive nivolumab IV over 30 minutes every 3 weeks and ipilimumab IV every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM VII (ADVANCED RENAL CELL CARCINOMA [RCC]): Patients receive nivolumab IV over 30 minutes in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy in the absence of disease progression or unacceptable toxicity. Patients may continue to receive single agent nivolumab every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity. Patients may optionally receive nivolumab IV every 2 or 4 weeks in combination with cabozantinib orally (PO) once daily (QD) for up to 2 years of combination therapy in the absence of disease progression or unacceptable toxicity. Treatment with single agent cabozantinib may continue in the absence of disease progression or unacceptable toxicity.
ARM VIII (MICROSATELLITE INSTABILITY-HIGH [MSI-H] OR MISMATCH REPAIR DEFICIENT [dMMR] METASTATIC COLORECTAL CANCER): Patient receive nivolumab IV over 30 minutes every 2 or 4 weeks in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy in the absence of disease progression or unacceptable toxicity. Patients may continue to receive single agent nivolumab every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity.
ARM IX (HEPATOCELLULAR CARCINOMA [HCC]): Patients receive nivolumab IV over 30 minutes in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy. Patients may continue to receive single agent nivolumab every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity.
ARM X (ESOPHAGEAL SQUAMOUS CELL CARCINOMA): Patients receive nivolumab IV over 30 minutes every 2 or 4 weeks in combination with fluoropyrimidine and platinum-containing chemotherapy for up to 2 years in the absence of disease progression or unacceptable toxicity OR receive nivolumab IV every 2 or 3 weeks in combination with ipilimumab IV every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may then continue receiving fluoropyrimidine and platinum-containing chemotherapy in the absence of disease progression or unacceptable toxicity.
ARM XI (GASTRIC CANCER, GASTROESOPHAGEAL JUNCTION CANCER, AND ESOPHAGEAL ADENOCARCINOMA): Patients receive nivolumab IV over 30 minutes in combination with fluoropyrimidine and platinum-containing chemotherapy every 2 or 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Patients also undergo collection of blood, cerebrospinal fluid (CSF), tissue, stool, and urine samples throughout the trial.
After completion of study treatment, patients without disease progression are followed for 100 days, and patients with disease progression are followed every 12 weeks for up to 5 years.
- Conditions
- Autoimmune Disease, Crohn Disease, Dermatomyositis, Hematopoietic and Lymphoid Cell Neoplasm, Inflammatory Bowel Disease, Malignant Solid Neoplasm
- Being tested
- Biospecimen Collection, Cabozantinib, Fluoropyrimidine, Ipilimumab, Nivolumab
- Medical subject headings
- Autoimmune Diseases, Crohn Disease, Dermatomyositis, Hematologic Neoplasms, Inflammatory Bowel Diseases, Multiple Sclerosis, Psoriasis, Arthritis, Psoriatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo collection of blood, CSF, tissue, stool and urine samples
CabozantinibDrug
Given PO
FluoropyrimidineDrug
Given fluoropyrimidine
IpilimumabBiological
Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016
Given IV
NivolumabBiological
Also called ABP 206, BCD-263, BMS 936558, BMS-936558
Given IV
Platinum CompoundDrug
Also called Platinum Agents, Platinum-Based Chemotherapeutic Agent
Given platinum containing chemotherapy
Platinum DoubletDrug
Also called Platinum Doublets, Platinum-based Chemotherapy Doublet, Platinum-based Chemotherapy Doublets, Platinum-based Double Chemotherapy Combination
Given platinum doublet
| Study group | Role | What they receive |
|---|---|---|
| Arm I (nivolumab) | Experimental | Patients may receive single agent nivolumab IV over 30 minutes every 4 weeks for up to 2 years for patients with metastatic indications, for up to 1 year for adjuvant indications or for up to 3 months after surgery for neoadjuvant indications in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial. Receives: Procedure: Biospecimen Collection; Biological: Nivolumab |
| Arm II (nivolumab, ipilimumab) | Experimental | Patients with unresectable or metastatic melanoma receive nivolumab IV over 30 minutes every 2 or 4 weeks in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab may continue every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial. Receives: Procedure: Biospecimen Collection; Biological: Ipilimumab; Biological: Nivolumab |
| Arm III (nivolumab, platinum doublet) | Experimental | Patients receiving neoadjuvant treatment of resectable NSCLC receive nivolumab IV over 30 minutes in combination with platinum doublet therapy every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial. Receives: Procedure: Biospecimen Collection; Biological: Nivolumab; Drug: Platinum Doublet |
| Arm IV (nivolumab, ipilimumab) | Experimental | Patients with metastatic PD-L1 positive NSCLC receive nivolumab IV over 30 minutes every 3 weeks and ipilimumab IV every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial. Receives: Procedure: Biospecimen Collection; Biological: Ipilimumab; Biological: Nivolumab |
| Arm IX (nivolumab, ipilimumab) | Experimental | Patients with HCC receive nivolumab IV over 30 minutes in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy. Patients may continue to receive single agent nivolumab every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial. Receives: Procedure: Biospecimen Collection; Biological: Ipilimumab; Biological: Nivolumab |
| Arm V (nivolumab, ipilimumab, platinum doublet therapy) | Experimental | Patients with metastatic or recurrent NSCLC receive nivolumab IV over 30 minutes every 3 weeks, ipilimumab IV every 6 weeks and platinum doublet therapy every 3 weeks for up to 2 cycles of combination therapy. Treatment with nivolumab and ipilimumab repeats for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial. Receives: Procedure: Biospecimen Collection; Biological: Ipilimumab; Biological: Nivolumab; Drug: Platinum Doublet |
| Arm VI (nivolumab, ipilimumab) | Experimental | Patients with malignant pleural mesothelioma receive nivolumab IV over 30 minutes every 3 weeks and ipilimumab IV every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial. Receives: Procedure: Biospecimen Collection; Biological: Ipilimumab; Biological: Nivolumab |
| Arm VII (nivolumab, ipilimumab, cabozantinib) | Experimental | Patients with advanced RCC receive nivolumab IV over 30 minutes in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy in the absence of disease progression or unacceptable toxicity. Patients may continue to receive single agent nivolumab every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity. Patients may optionally receive nivolumab IV every 2 or 4 weeks in combination with cabozantinib PO QD for up to 2 years of combination therapy in the absence of disease progression or unacceptable toxicity. Treatment with single agent cabozantinib may continue in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial. Receives: Procedure: Biospecimen Collection; Drug: Cabozantinib; Biological: Ipilimumab; Biological: Nivolumab |
| Arm VIII (nivolumab, ipilimumab) | Experimental | Patients with MSI-H or dMMR metastatic colorectal cancer receive nivolumab IV over 30 minutes every 2 or 4 weeks in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy in the absence of disease progression or unacceptable toxicity. Patients may continue to receive single agent nivolumab every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial. Receives: Procedure: Biospecimen Collection; Biological: Ipilimumab; Biological: Nivolumab |
| Arm X (nivolumab, fluoropyrimidine, platinum, ipilimumab) | Experimental | Patients with esophageal squamous cell carcinoma receive nivolumab IV over 30 minutes every 2 or 4 weeks in combination with fluoropyrimidine and platinum-containing chemotherapy for up to 2 years in the absence of disease progression or unacceptable toxicity OR receive nivolumab IV every 2 or 3 weeks in combination with ipilimumab IV every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may then continue receiving fluoropyrimidine and platinum-containing chemotherapy in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial. Receives: Procedure: Biospecimen Collection; Drug: Fluoropyrimidine; Biological: Ipilimumab; Biological: Nivolumab; Drug: Platinum Compound |
| Arm XI (nivolumab, fluoropyrimidine, platinum) | Experimental | Patients with gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma receive nivolumab IV over 30 minutes in combination with fluoropyrimidine and platinum-containing chemotherapy every 2 or 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial. Receives: Procedure: Biospecimen Collection; Drug: Fluoropyrimidine; Biological: Nivolumab; Drug: Platinum Compound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Will be reported overall and by severity, and dose limiting toxicities will be summarized for all patients and by disease severity cohort.
Measured: Up to 100 days after completion of study treatment
Change in disease assessments
Will be summarized at each time point for each disease severity cohort.
Measured: Baseline up to 100 days after completion of study treatment
Overall response rate
Will be computed along with its associated exact 95% confidence interval for all patients and by disease severity cohort.
Measured: Up to 5 years after completion of study treatment
Changes in serum chemokines and circulating immune cells over time
Will be summarized and assessed using generalized linear mixed modeling.
Measured: Baseline up to 100 days after completion of study treatment
Gene expression in normal tissues
Will be compared with gene expression in malignant tissues based on two-sample t-test and Wilcoxon rank sum test. False discovery rate, if appropriate, will be used to control for multiple testing.
Measured: Up to 100 days after completion of study treatment
Clinical measures of interest
The association between demographic and clinical measures of interest with overall response rate and toxicity will be evaluated using logistic regression modeling to identify potential predictors of outcomes.
Measured: Up to 100 days after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2019
- Study start16 Jul 2019
- Primary completion30 Mar 2028 (estimated)
- Study completion30 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Autoimmune DiseaseStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Hussein A Tawbi, Principal investigator, University of Texas MD Anderson Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03816345
- Sponsor's protocol ID
- NCI-2019-00241
- Other IDs
- NCI-2019-00241, 10204, 10204, UM1CA186688
- Status last verified
- Sep 2026
- First submitted
- 24 Jan 2019
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
Publications
Vaziri H, Turshudzhyan A, Vecchio E. Immunotherapy-induced Colitis: A Comprehensive Review of Epidemiology, Clinical Presentation, Diagnostic Workup, and Management Plan. J Clin Gastroenterol. 2022 Aug 1;56(7):555-564. doi: 10.1097/MCG.0000000000001705. Epub 2022 Apr 21.
PubMed 35470301