Clinical Trials /

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

NCT03816345

Description:

This phase Ib trial studies the side effects of nivolumab and to see how well it works in treating patients with autoimmune disorders or 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.

Related Conditions:
  • Bladder Carcinoma
  • Cervical Carcinoma
  • Gastric Carcinoma
  • Head and Neck Carcinoma
  • Hepatocellular Carcinoma
  • Hodgkin Lymphoma
  • Malignant Solid Tumor
  • Melanoma
  • Merkel Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab in Treating Patients With Autoimmune Disorders or Advanced, Metastatic, or Unresectable Cancer
  • Official Title: A Phase Ib Study of Nivolumab in Patients With Autoimmune Disorders and Advanced Malignancies (AIM-NIVO)

Clinical Trial IDs

  • ORG STUDY ID: NCI-2019-00241
  • SECONDARY ID: NCI-2019-00241
  • SECONDARY ID: 10204
  • SECONDARY ID: 10204
  • SECONDARY ID: UM1CA186688
  • NCT ID: NCT03816345

Conditions

  • Advanced Malignant Neoplasm
  • Autoimmune Disease
  • Crohn Disease
  • Dermatomyositis
  • Inflammatory Bowel Disease
  • Metastatic Malignant Neoplasm
  • Multiple Sclerosis
  • Rheumatoid Arthritis
  • Sjogren Syndrome
  • Systemic Lupus Erythematosus
  • Systemic Scleroderma
  • Ulcerative Colitis
  • Unresectable Malignant Neoplasm

Interventions

DrugSynonymsArms
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (nivolumab)

Purpose

This phase Ib trial studies the side effects of nivolumab and to see how well it works in treating patients with autoimmune disorders or 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.

Detailed Description

      PRIMARY OBJECTIVES:

      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 determine 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 provide dosing recommendations for
      anti-PD-1 antibodies based on the severity of the autoimmune disorder.

      IV. To determine 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab)ExperimentalPatients receive nivolumab IV over 30 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Nivolumab

Eligibility Criteria

        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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 100 days
Safety Issue:
Description:Will be reported overall and by severity, and dose limiting toxicities will be summarized for all patients and by disease severity cohort.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:National Cancer Institute (NCI)

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