Nivolumab in Treating Patients With Autoimmune Disorders and Advanced, Metastatic, or Unresectable Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT03816345

Collaborator

(none)

312

Enrollment

Locations

Arm

40.9

Anticipated Duration (Months)

6.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase Ib trial studies the side effects of nivolumab and to see how well it works in treating patients with autoimmune disorders and cancer that has spread to other places in the body or cannot removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignant Solid Neoplasm Autoimmune Disease Crohn Disease Dermatomyositis Hematopoietic and Lymphoid Cell Neoplasm Inflammatory Bowel Disease Metastatic Malignant Solid Neoplasm Multiple Sclerosis Rheumatoid Arthritis Sjogren Syndrome Systemic Lupus Erythematosus Systemic Scleroderma Ulcerative Colitis Unresectable Malignant Solid Neoplasm	Biological: Nivolumab	Phase 1

Detailed Description

PRIMARY OBJECTIVE:

To assess the overall safety, including the incidence of dose-limiting toxicity (DLT), and other 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], 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, and other autoimmune diseases.
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.
To evaluate the impact of nivolumab on the disease severity indices for: DM/SSc, RA, SLE, IBD: UC and CD, not specified (NS), MS.
To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, ribonucleic acid (RNA) sequencing, in order to: identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned, and identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and ribonucleic acid (RNA)-based assessment platforms.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 100 days.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

312 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase Ib Study of Nivolumab in Patients With Autoimmune Disorders and Advanced Malignancies (AIM-NIVO)

Actual Study Start Date :

Apr 4, 2019

Anticipated Primary Completion Date :

Aug 31, 2022

Anticipated Study Completion Date :

Aug 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (nivolumab) Patients receive nivolumab IV over 30 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Biological: Nivolumab Given IV Other Names: BMS-936558 CMAB819 MDX-1106 NIVO Nivolumab Biosimilar CMAB819 ONO-4538 Opdivo

Arm

Intervention/Treatment

Experimental: Treatment (nivolumab)

Patients receive nivolumab IV over 30 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Nivolumab

Given IV

Other Names:

BMS-936558

CMAB819

MDX-1106

NIVO

Nivolumab Biosimilar CMAB819

ONO-4538

Opdivo

Outcome Measures

Primary Outcome Measures

Incidence of adverse events [Up to 100 days]
Will be reported overall and by severity, and dose limiting toxicities will be summarized for all patients and by disease severity cohort.
Change in disease assessments [Baseline up to 100 days]
Will be summarized at each time point for each disease severity cohort.
Overall response rate [Up to 100 days]
Will be computed along with its associated exact 95% confidence interval for all patients and by disease severity cohort.
Changes in serum chemokines and circulating immune cells over time [Baseline up to 100 days]
Will be summarized and assessed using generalized linear mixed modeling.
Gene expression in normal tissues [Up to 100 days]
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.
Clinical measures of interest [Up to 100 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable. 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 is Food and Drug Administration (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 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 >=

Life expectancy of greater than 12 weeks
Leukocytes >= 2,000/mcL
Absolute neutrophil count >= 1,500/mcL
Platelets >= 100,000/mcL
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN unless the patient has dermatomyositis and in the opinion of the investigator the elevation is due to diabetes mellitus (DM)
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 treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) during the screening period. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required 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) 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
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Patients who have had chemotherapy or radiotherapy within 4 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, 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 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 who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) bleeding, obstruction, and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study. For the IBD (UC and CD) cohort, an endoscopic assessment, disease activity index, and disease specific inclusion/exclusion criteria will substitute for these factors in determining eligibility with the exception of abdominal carcinomatosis, which should prompt further evaluation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	Stanford Cancer Institute Palo Alto	Palo Alto	California	United States	94304
3	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
4	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut	United States	06510
5	Yale University	New Haven	Connecticut	United States	06520
6	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	United States	30322
7	Northwestern University	Chicago	Illinois	United States	60611
8	University of Kansas Clinical Research Center	Fairway	Kansas	United States	66205
9	HaysMed University of Kansas Health System	Hays	Kansas	United States	67601
10	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
11	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
12	Olathe Health Cancer Center	Olathe	Kansas	United States	66061
13	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas	United States	66210
14	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas	United States	66211
15	Ascension Via Christi - Pittsburg	Pittsburg	Kansas	United States	66762
16	Salina Regional Health Center	Salina	Kansas	United States	67401
17	University of Kansas Health System Saint Francis Campus	Topeka	Kansas	United States	66606
18	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas	United States	66205
19	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
20	National Cancer Institute Developmental Therapeutics Clinic	Bethesda	Maryland	United States	20892
21	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892
22	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
23	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
24	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
25	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri	United States	63141
26	Truman Medical Centers	Kansas City	Missouri	United States	64108
27	University of Kansas Cancer Center - North	Kansas City	Missouri	United States	64154
28	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri	United States	64064
29	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri	United States	64116
30	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
31	Siteman Cancer Center-South County	Saint Louis	Missouri	United States	63129
32	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri	United States	63136
33	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri	United States	63376
34	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
35	NYU Winthrop Hospital	Mineola	New York	United States	11501
36	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
37	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
38	NYP/Weill Cornell Medical Center	New York	New York	United States	10065
39	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
40	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
41	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
42	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas	United States	76104
43	M D Anderson Cancer Center	Houston	Texas	United States	77030
44	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas	United States	75080
45	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
46	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
47	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9