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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03816345
• Other study ID #: NCI-2019-00241
• Secondary ID: NCI-2019-0024110
• Status: Recruiting
• Phase: Phase 1
• Start date: July 16, 2019
• Est. completion date: August 31, 2024

Study information

• Verified date: April 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

PRIMARY OBJECTIVE:

I. 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.

SECONDARY OBJECTIVES:

I. 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.

V. To identify biomarkers of response and toxicity.

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. Patients also undergo collection of blood, cerebrospinal fluid (CSF), tissue, stool, and urine samples throughout the trial.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: August 31, 2024
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. 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 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 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) 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

• 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

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Autoimmune Disease
• Autoimmune Diseases
• Crohn Disease
• Dermatomyositis
• Hematopoietic and Lymphoid Cell Neoplasm
• Inflammatory Bowel Disease
• Inflammatory Bowel Diseases
• Lupus Erythematosus, Systemic
• Malignant Solid Neoplasm
• Multiple Sclerosis
• Neoplasms
• Psoriasis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sjogren Syndrome
• Sjogren's Syndrome
• Systemic Lupus Erythematosus
• Systemic Scleroderma
• Ulcerative Colitis

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood, CSF, tissue, stool and urine samples

Biological:
• Nivolumab
Given IV

Locations

Country	Name	City	State
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	National Cancer Institute Developmental Therapeutics Clinic	Bethesda	Maryland
United States	National Institutes of Health Clinical Center	Bethesda	Maryland
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	UT Southwestern Simmons Cancer Center - RedBird	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	University of Kansas Clinical Research Center	Fairway	Kansas
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	HaysMed	Hays	Kansas
United States	M D Anderson Cancer Center	Houston	Texas
United States	University Health Truman Medical Center	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	NYU Langone Hospital - Long Island	Mineola	New York
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 100 days
Primary	Change in disease assessments	Will be summarized at each time point for each disease severity cohort.	Baseline up to 100 days
Primary	Overall response rate	Will be computed along with its associated exact 95% confidence interval for all patients and by disease severity cohort.	Up to 100 days
Primary	Changes in serum chemokines and circulating immune cells over time	Will be summarized and assessed using generalized linear mixed modeling.	Baseline up to 100 days
Primary	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.	Up to 100 days
Primary	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.	Up to 100 days