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

Phase 1

Recruiting

• Conditions: Autoimmune Disease; Crohn Disease; Dermatomyositis; Hematopoietic and Lymphoid Cell Neoplasm; Inflammatory Bowel Disease; Malignant Solid Neoplasm; Multiple Sclerosis; Psoriasis; Psoriatic Arthritis; Rheumatoid Arthritis

• Registration Number: NCT03816345
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-1-24
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Inclusion Criteria:<br><br> - Patients can have either histologically confirmed malignancy that is radiologically<br> evaluable and metastatic or unresectable, or have a malignancy for which a<br> PD-1/PD-L1 inhibitor has been approved in the adjuvant setting. Eligible tumor types<br> include solid tumors and malignancies in which there is known evidence of clinical<br> activity for single agent PD-1 or PD-L1 antibodies. Nivolumab is Food and Drug<br> Administration (FDA)-approved for the treatment of melanoma, non-small cell lung<br> cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC),<br> gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck<br> cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any<br> solid tumor with microsatellite instability (MSI)-high status confirmed. Patients<br> with HL are eligible but must follow standard response criteria. Additional tumor<br> types may be eligible on a case by case basis upon discussion with principal<br> investigator (PI). Patients enrolling on the trial for adjuvant use will be<br> restricted to those with histology for which a PD-1/PD-L1 inhibitor has been<br> approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC,<br> cervical cancer, and bladder cancer<br><br> - Patients who have previously received other forms of immunotherapy (high-dose [HD]<br> IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine<br> immunotherapy for at least 4 weeks before nivolumab administration. Patients who<br> have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks<br><br> - Age >= 18 years; children are excluded from this study but may be eligible for<br> future pediatric phase 1 combination trials<br><br> - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky >=<br> 60)<br><br> - Life expectancy of greater than 12 weeks<br><br> - Leukocytes >= 1,000/mcL<br><br> - Absolute neutrophil count >= 500/mcL<br><br> - Platelets >= 50,000/mcL<br><br> - Total bilirubin =< 2 x institutional upper limit of normal (ULN)<br><br> - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase<br> [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase<br> [SGPT]) =< 5 x institutional ULN or =< 8 x institutional ULN for patients with liver<br> metastases or an autoimmune disease that is contributing to the elevation of these<br> values<br><br> - Creatinine ULN OR glomerular filtration rate (GFR) >= 30 mL/min (if using the<br> Cockcroft-Gault formula)<br><br> - Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral<br> therapy with undetectable viral load within 6 months are eligible for this trial<br><br> - If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be<br> undetectable on suppressive therapy if indicated<br><br> - If history of hepatitis C virus (HCV) infection, must be treated with undetectable<br> HCV viral load<br><br> - Patients with new or progressive brain metastases (active brain metastases) or<br> leptomeningeal disease are eligible if the treating physician determines that<br> immediate central nervous system (CNS) specific treatment is not required and is<br> unlikely to be required for at least 4 weeks (or scheduled assessment after the<br> first cycle of treatment), and a risk-benefit analysis (discussion) by the patient<br> and the investigator favors participation in the clinical trial<br><br> - The effects of nivolumab on the developing human fetus are unknown. For this reason,<br> women of child-bearing potential (WOCBP) and men must agree to use adequate<br> contraception (hormonal or barrier method of birth control; abstinence) prior to<br> study entry and for the duration of study participation. WOCBP receiving nivolumab<br> will be instructed to adhere to contraception for a period of 5 months after the<br> last dose of investigational product. Men receiving nivolumab and who are sexually<br> active with WOCBP will be instructed to adhere to contraception for a period of 7<br> months after the last dose of investigational product. Women of childbearing<br> potential must have a negative serum or urine pregnancy test (minimum sensitivity 25<br> IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours<br> prior to the start of nivolumab. Women must not be breastfeeding. Women who are not<br> of childbearing potential (i.e., who are postmenopausal or surgically sterile as<br> well as azoospermic men) do not require contraception. WOCBP is defined as any<br> female who has experienced menarche and who has not undergone surgical sterilization<br> (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is<br> defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of<br> other biological or physiological causes. In addition, women under the age of 55<br> must have a documented serum follicle stimulating hormone (FSH) level less than 40<br> mIU/mL. These durations have been calculated using the upper limit of the half-life<br> for nivolumab (25 days) and are based on the protocol requirement that WOCBP use<br> contraception for 5 half-lives plus 30 days, and men who are sexually active with<br> WOCBP use contraception for 5 half-lives plus 90 days. Should a woman become<br> pregnant or suspect she is pregnant while she or her partner is participating in<br> this study, she (or the participating partner) should inform the treating physician<br> immediately<br><br> - Ability to understand and the willingness to sign a written informed consent<br> document<br><br> - Patients with more than one autoimmune disease are eligible. The treating physician<br> would determine which autoimmune disease is dominant and the patient would be<br> treated under that specific cohort<br><br>Exclusion Criteria:<br><br> - Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for<br> nitrosoureas or mitomycin C) prior to entering the study or those who have not<br> recovered from adverse events (AEs) due to agents administered more than 4 weeks<br> earlier have not resolved or stabilized. Palliative (limited-field) radiation<br> therapy (RT) is permitted (2 week washout from start of treatment), if all of the<br> following criteria are met:<br><br> - Repeat imaging demonstrates no new sites of bone metastases<br><br> - The lesion being considered for palliative radiation is not a target lesion<br><br> - Patients with prior therapy with an anti-PD-1 or anti-PD-L1<br><br> - Patients with prior allogeneic hematologic transplant<br><br> - Patients who are receiving any other anticancer investigational agents<br><br> - Uncontrolled intercurrent illness including, but not limited to, ongoing or active<br> infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac<br> arrhythmia, or psychiatric illness/social situations that would limit compliance<br> with study requirements

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events;Change in disease assessments;Overall response rate;Changes in serum chemokines and circulating immune cells over time;Gene expression in normal tissues;Clinical measures of interest