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

  • STATUS
    Recruiting
  • End date
    Aug 31, 2022
  • participants needed
    312
  • sponsor
    National Cancer Institute (NCI)
Updated on 22 September 2021
diabetes
ct scan
cancer
total bilirubin
hysterectomy
lymphoma
absolute neutrophil count
monoclonal antibodies
cytokines
carcinoma
interleukin-2
lung cancer
computed tomography
MRI
glomerular filtration rate
white blood cells
human chorionic gonadotropin
metastasis
neutrophil count
tumor cells
brain metastases
pd-l1
follicle stimulating hormone
gastric cancer
nivolumab
solid tumor
head and neck cancer
autoimmune disease
bladder cancer
hepatitis c virus
nervous
computerized tomography
dermatomyositis
disease or disorder
diabetes mellitus (dm)

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, 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:

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, 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.

V. 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.

Details
Condition Gastroenteritis, Intestinal Diseases, Dermatomyositis, Hematologic Malignancy, Multiple Sclerosis, Autoimmune disease, CONNECTIVE TISSUE DISEASE, Sicca Syndrome, Rheumatoid Arthritis, Scleroderma, Systemic sclerosis, Dermatosis, SYSTEMIC LUPUS ERYTHEMATOSUS, Ulcerative Colitis, Autoimmunity, Inflammatory bowel disease, Crohn's Disease, Polymyositis, Rheumatoid Arthritis (Pediatric), Dermatomyositis (Connective Tissue Disease), Advanced Solid Tumor, Advanced Cancer, Metastatic Malignant Solid Neoplasm, Advanced Malignant Solid Neoplasm, Metastatic Malignant Neoplasm, Unresectable Malignant Neoplasm, Advanced Malignant Neoplasm, Congenital Skin Diseases, Cancer, Metastatic, Metastatic Solid Tumor, Polymyositis (Inflammatory Muscle Disease), Crohn's Disease (Pediatric), Ulcerative Colitis (Pediatric), Radiologically Isolated Syndrome, Unresectable Malignant Solid Neoplasm, Advanced Malignant Solid Tumor, Dermatite Atopique modérée ou grave, Sjogren's Syndrome, Skin Conditions, Blood Cancer, Connective Tissue Diseases, Hematologic Cancer, Bowel Dysfunction, Hematologic Neoplasms, hematopoietic and lymphoid cell neoplasm, cancer advanced, multiple sclerosis (ms), inflammatory bowel diseases, autoimmune diseases, autoimmune disorder, autoimmune disorders, crohns disease, metastatic malignant solid tumor, hematopoietic malignancy, progressive systemic sclerosis
Treatment Nivolumab
Clinical Study IdentifierNCT03816345
SponsorNational Cancer Institute (NCI)
Last Modified on22 September 2021

Eligibility

Yes No Not Sure

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 >= 60)
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
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