Clinical Trials /

Ibrutinib and Nivolumab in Treating Patients With Previously-Treated Metastatic Kidney Cancer

NCT02899078

Description:

This phase Ib/II trial studies how well ibrutinib and nivolumab work in treating patients with previously-treated kidney cancer that has spread to other parts of 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 patients with metastatic kidney cancer.

Related Conditions:
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ibrutinib and Nivolumab in Treating Patients With Previously-Treated Metastatic Kidney Cancer
  • Official Title: Phase Ib/II Trial of Ibrutinib Plus Nivolumab in Patients With Previously-Treated Metastatic Renal Cell Cancer

Clinical Trial IDs

  • ORG STUDY ID: UCDCC#262
  • SECONDARY ID: NCI-2016-01266
  • SECONDARY ID: UCDCC#262
  • NCT ID: NCT02899078

Conditions

  • Metastatic Renal Cell Cancer
  • Stage IV Renal Cell Cancer

Interventions

DrugSynonymsArms
IbrutinibBTK Inhibitor PCI-32765, CRA-032765, IMBRUVICATreatment (ibrutinib, nivolumab)
NivolumabBMS-936558, MDX-1106, Opdivo, NIVOTreatment (ibrutinib, nivolumab)

Purpose

This phase Ib/II trial studies how well ibrutinib and nivolumab work in treating patients with previously-treated kidney cancer that has spread to other parts of 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 patients with metastatic kidney cancer.

Detailed Description

      PRIMARY OBJECTIVE:

      To assess in a preliminary fashion the feasibility and efficacy of ibrutinib in combination
      with nivolumab in patients with previously-treated metastatic renal cell cancer (mRCC).

      SECONDARY OBJECTIVE:

      To evaluate the safety of the combination of ibrutinib and nivolumab in patients with
      previously treated mRCC.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ibrutinib, nivolumab)ExperimentalPatients receive ibrutinib PO QD on days 1-28 and nivolumab intravenously IV over 60 minutes on days 1 and 15. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
  • Ibrutinib
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Metastatic renal cell cancer patients (any histologic subtype) with measurable and/or
             evaluable disease who have completed at least one line of prior systemic therapy are
             potentially eligible for this trial; any number of prior systemic therapies are
             allowed, including prior nivolumab

          -  Absolute neutrophil count > 750 cells/mm^3 (0.75 x 10^9/L)

          -  Platelet count > 50,000 cells/mm^3 (50 x 10^9/L)

          -  Hemoglobin > 8.0 g/dL

          -  Serum aspartate transaminase (aspartate aminotransferase [AST]) or alanine
             transaminase (alanine aminotransferase [ALT]) =< 3.0 x upper limit of normal (ULN)

          -  Estimated creatinine clearance >= 30 ml/min (Cockcroft-Gault)

          -  Bilirubin =< 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of
             non-hepatic origin)

          -  Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x ULN and partial
             thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) < 1.5 x ULN

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

          -  Female subjects who are of non-reproductive potential (i.e., post-menopausal by
             history - no menses for >= 1 year; OR history of hysterectomy; OR history of
             bilateral tubal ligation; OR history of bilateral oophorectomy); female subjects of
             childbearing potential must have a negative serum pregnancy test upon study entry

          -  Male and female subjects who agree to use both a highly effective methods of birth
             control (e.g., implants, injectables, combined oral contraceptives, some intrauterine
             devices [IUDs], sexual abstinence, or sterilized partner) and a barrier method (e.g.,
             condoms, cervical ring, sponge, etc.) during the period of therapy and for 30 days
             after the last dose of study drug

        Exclusion Criteria:

          -  Cytotoxic chemotherapy =< 21 days prior to first administration of study treatment
             and/or monoclonal antibody =< 4 weeks prior to first administration of study
             treatment and/or other renal cell carcinoma (RCC)-directed systemic therapy =< 2
             weeks prior to first administration of study treatment

          -  History of other malignancies, except:

               -  Malignancy treated with curative intent and with no known active disease present
                  for >= 3 years before the first dose of study drug and felt to be at low risk
                  for recurrence by treating physician

               -  Adequately treated non-melanoma skin cancer or lentigo malignancy without
                  evidence of disease

               -  Adequately treated carcinoma in situ or T1 urothelial cancer without evidence of
                  disease

          -  Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus,
             etc., or chronic administration [> 14 days] of > 10 mg/day of prednisone) within 28
             days of the first dose of study drug

          -  Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug

          -  Recent infection requiring systemic treatment that was completed =< 14 days before
             the first dose of study drug

          -  Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved
             to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade =< 1, or
             to the levels dictated in the inclusion/exclusion criteria with the exception of
             alopecia

          -  Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia

          -  History of stroke or intracranial hemorrhage within 6 months prior to enrollment

          -  Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus
             (HCV) or hepatitis B virus (HBV); subjects who are positive for hepatitis B core
             antibody or hepatitis B surface antigen must have a negative polymerase chain
             reaction (PCR) result before enrollment; those who are PCR positive will be excluded

          -  Any uncontrolled active systemic infection

          -  Major surgery within 4 weeks of first dose of study drug

          -  Any life-threatening illness, known autoimmune disease, medical condition, or organ
             system dysfunction that, in the investigator's opinion, could compromise the
             subject's safety or put the study outcomes at undue risk

          -  Currently active, clinically significant cardiovascular disease, such as uncontrolled
             arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart
             Association Functional Classification; or a history of myocardial infarction,
             unstable angina, or acute coronary syndrome within 6 months prior to enrollment

          -  Unable to swallow capsules or malabsorption syndrome, disease significantly affecting
             gastrointestinal function, or resection of the stomach or small bowel, symptomatic
             inflammatory bowel disease or ulcerative colitis, or partial or complete bowel
             obstruction

          -  Lactating or pregnant

          -  Unwilling or unable to participate in all required study evaluations and procedures

          -  Unable to understand the purpose and risks of the study and to provide a signed and
             dated informed consent form (ICF) and authorization to use protected health
             information (in accordance with national and local subject privacy regulations)

          -  Concomitant use of warfarin or other vitamin K antagonists; Note: Subjects receiving
             antiplatelet agents in conjunction with ibrutinib should be observed closely for any
             signs of bleeding or bruising, and ibrutinib should be withheld in the event of any
             bleeding events; supplements such as fish oil and vitamin E preparations should be
             avoided

          -  Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor

          -  QT prolongation and/or familiar history of QT prolongation and uncontrolled cardiac
             arrhythmias

          -  Currently active, clinically significant hepatic impairment Child-Pugh class B or C
             according to the Child Pugh classification
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:From baseline to death or progression, assessed for up to 6 months
Safety Issue:
Description:The duration of PFS will be summarized descriptively using Kaplan-Meier survival plots and life tables. The number and proportion with PFS of 6 months or more will be reported, adjusting for censoring using the life-table approach.

Secondary Outcome Measures

Measure:Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
Time Frame:Up to 30 days
Safety Issue:
Description:Number and type of adverse events will be summarized descriptively by system organ class affected and by grade of event, overall and by dose.
Measure:Overall survival
Time Frame:Up to 6 months
Safety Issue:
Description:Will be summarized descriptively by Kaplan-Meier curves and life table estimates.
Measure:Response
Time Frame:Up to 6 months
Safety Issue:
Description:Assessed by RECIST version 1.1

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of California, Davis

Last Updated

November 17, 2016