Clinical Trials /

Ibrutinib and Nivolumab in Treating Participants With Metastatic Solid Tumors

NCT03525925

Description:

This phase I trial studies how well ibrutinib and nivolumab work in treating participants with solid tumors that have spread to other places in the body. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving ibrutinib and nivolumab may work better in treating participants with solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Ibrutinib and Nivolumab in Treating Participants With Metastatic Solid Tumors
  • Official Title: Pilot Study Testing the Effects of BTK Inhibitor Ibrutinib on Levels and Function of Myeloid Derived Suppressor Cells and Other Immune Subsets in Patients With Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: OSU-18015
  • SECONDARY ID: NCI-2018-00423
  • SECONDARY ID: P30CA016058
  • NCT ID: NCT03525925

Conditions

  • Metastatic Malignant Solid Neoplasm

Interventions

DrugSynonymsArms
IbrutinibBTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765Treatment (ibrutinib, nivolumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (ibrutinib, nivolumab)

Purpose

This phase I trial studies how well ibrutinib and nivolumab work in treating participants with solid tumors that have spread to other places in the body. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving ibrutinib and nivolumab may work better in treating participants with solid tumors.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Evaluate the effect of the ibrutinib therapy on circulating levels of myeloid derived
      suppressor cells MDSC.

      SECONDARY OBJECTIVES:

      I. Assess safety of the study combination in study subjects.

      EXPLORATORY OBJECTIVES:

      I. Evaluate the effect of the ibrutinib/nivolumab therapy on circulating levels of MDSC.

      II. Evaluate the effect of the ibrutinib and ibrutinib/nivolumab therapy on the
      immunosuppressive function of circulating MDSC by measuring their ability to inhibit T cell
      proliferation and natural killer cell mediated antibody dependent cell cytotoxicity.

      III. Study the effect of ibrutinib and ibrutinib/nivolumab therapy on levels of circulating
      innate and adaptive immune cells such as natural killer cell and T lymphocyte subsets.

      IV. Study circulating MDSC levels at the time of disease progression. V. Evaluate in a
      preliminary fashion the effect of the regimen on progression-free survival.

      OUTLINE:

      Participants receive ibrutinib orally (PO) daily for 15 days. After 7 days receiving
      ibrutinib, participants receive nivolumab intravenously (IV) over 60 minutes on days 1 and
      15. Courses with nivolumab repeat every 28 days in the absence of disease progression or
      unaccepted toxicity.

      After completion of study treatment, participants are followed up every 3 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ibrutinib, nivolumab)ExperimentalParticipants receive ibrutinib PO daily for 15 days. After 7 days receiving ibrutinib, participants receive nivolumab IV over 60 minutes on days 1 and 15. Courses with nivolumab repeat every 28 days in the absence of disease progression or unaccepted toxicity.
  • Ibrutinib
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with biopsy-proven metastatic solid tumor and be eligible to receive
             nivolumab per standard of care

          -  Patients will be allowed to have any number of prior lines of therapy for metastatic
             cancer

          -  Patients with measurable and non-measurable disease are allowed to participate

          -  Absolute neutrophil count (ANC) ? 1.5 x 10^3/mm^3

          -  Hemoglobin (Hgb) ? 9 g/dL

          -  Platelet count ? 100 x10^3/mm^3

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ? 2.5 x upper limit of
             normal (ULN) or ? 5 x ULN in patients with liver metastases

          -  Prothrombin time ? 1.5 x ULN

          -  Total bilirubin ? 1.5 x ULN (unconjugated bilirubin of < 3 x ULN for patients with
             known Gilbert syndrome)

          -  Creatinine clearance of ? 50 ml/min by Cockcroft-Gault equation

          -  Corrected QT interval of < 480 msec (using either Bazett?s or Fridericia's formula)

          -  Life expectancy of > 12 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 ? 2

          -  Sexually active women with child bearing potential must have a negative pregnancy test
             obtained within 14 days prior to initiating study treatment

          -  Sexually active women of child-bearing potential and men must agree to use adequate
             contraception prior to study entry, for the duration of study participation and for 3
             months after completion of study treatment administration; adequate contraception
             includes methods such as oral contraceptives, double barrier method (condom plus
             spermicide or diaphragm), or abstaining from sexual intercourse

        Exclusion Criteria:

          -  History of prior therapy with ibrutinib or nivolumab

          -  Unable to swallow capsules or having disease that is significantly affecting
             gastrointestinal function and/or inhibiting small intestine absorption

          -  Diagnosis of congenital or acquired immunodeficiency with the exception of
             chemotherapy induced immune suppression

          -  Active autoimmune disease requiring systemic treatment within the past 3 months or a
             documented history of clinically severe autoimmune disease, or a syndrome that
             requires systemic steroids of greater than or equal to prednisone 10 mg/day or other
             immunosuppressive agents; patients with history of adequately treated Hashimoto?s
             thyroiditis will be eligible; patients requiring a short course of a high dose
             prednisone burst to treat asthma or common obstructive pulmonary disease will also be
             eligible 5 days following completion of the prednisone treatment

          -  Use of systemic steroids at a dose above 10 mg/day of prednisone or prednisone
             equivalent in cycle 1 of study therapy; systemic steroids must be discontinued at
             least 5 days prior to initiating study therapy; exception will be given to patients
             who develop immune related adverse events that necessitate use of steroids or other
             immune suppressive agents; following cycle 1 of study treatment, the use of systemic
             steroids will be allowed per discretion of the treating physician

          -  Active, non-infectious pneumonitis

          -  Ongoing or active infection requiring systemic therapy

          -  History of being positive for human immunodeficiency virus (HIV)

          -  History of hepatitis B or C

          -  History of receiving live vaccine within 30 days of planned start of study therapy

          -  Central nervous system (CNS) metastases or leptomeningeal carcinomatosis; patients
             with history of adequately treated brain metastases that are stable for > 2 weeks
             prior to the first dose of study regimen are eligible as long they no longer require
             steroids and have no seizures or worsening focal neurologic symptoms; anti-epileptic
             therapy will be allowed

          -  Patients who had prior systemic chemotherapy within 3 weeks (or < 5 half-lives ?
             whichever is longer)

          -  Prior radiation therapy within 2 weeks of study enrollment

          -  Prior investigational therapy within 4 weeks

          -  Major surgery within 4 weeks or minor surgery within 2 weeks prior to the first dose
             of study drug; port placement will not be considered major or minor surgery

          -  Any inter-current, uncontrolled systemic illness or any medical or psychiatric
             condition that in the opinion of the investigator would make the study therapy unsafe
             to the patient

          -  Unable to understand and sign informed consent form

          -  Uncontrolled, active cardiovascular disease including, but not limited to: symptomatic
             congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York
             Heart Association functional classification, unstable angina pectoris, cardiac
             arrhythmia

          -  Any medications or substances that are strong inhibitors or inducers of CYP 3A4 need
             to be discontinued prior to initiation the study therapy and for the duration of
             ibrutinib treatment; patients can resume these medications 3 days after completion of
             ibrutinib course

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition as ibrutinib or nivolumab
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Circulating levels of myeloid derived suppressor cells
Time Frame:Up to 2 years
Safety Issue:
Description:Will be summarized using descriptive statistics (N, mean, standard deviation, median, minimum, and maximum) and/or frequency and percentages for medically relevant categories. Changes of the continuous variables will be estimated using mixed model for repeated measures with proper data transformation as needed, and two-way tables and Chi-Square test will be used to summarize the changes of the categorical data.

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 2 years
Safety Issue:
Description:Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Will be presented using frequencies and percentages.
Measure:Progression free survival
Time Frame:Interval from study enrollment to first documented disease progression according to Response Evaluation Criteria in Solid Tumors 1.1 or death from any cause (whichever occurs first), assessed at 1 year
Safety Issue:
Description:One year progression free survival will be defined as proportion of patients who are free of disease progression or death (whichever occurs first) after 1 year of follow up. Progression free survival will be summarized using Kaplan and Meier methods, where patients who are event-free at the time of their last evaluation will be censored at that time point.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ohio State University Comprehensive Cancer Center

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