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

Sponsor
University of California, Davis (Other)
Overall Status
Completed
CT.gov ID
NCT02899078
Collaborator
Pharmacyclics LLC. (Industry)
31
Enrollment
1
Location
1
Arm
51.3
Actual Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
31 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase Ib/II Trial of Ibrutinib Plus Nivolumab in Patients With Previously-Treated Metastatic Renal Cell Cancer
Actual Study Start Date :
Nov 15, 2016
Actual Primary Completion Date :
Aug 5, 2020
Actual Study Completion Date :
Feb 24, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Treatment (ibrutinib, nivolumab)

Patients 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.

Drug: Ibrutinib
Given PO
Other Names:
  • BTK Inhibitor PCI-32765
  • CRA-032765
  • IMBRUVICA
  • Drug: Nivolumab
    Given IV
    Other Names:
  • BMS-936558
  • MDX-1106
  • Opdivo
  • NIVO
  • Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival (PFS) [From baseline to death or progression, assessed for up to 6 months]

      Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Secondary Outcome Measures

    1. National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 [Up to 30 days]

      Number of participants with adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03

    2. Overall Survival [Up to 32 months.]

      Overall survival, calculated using the Kaplan-Meier method as the duration from start of treatment to death by any cause.

    3. Response [Up to 6 months]

      Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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/mm3 (0.75 x 109/L)

    • Platelet count > 50,000 cells/mm3 (50 x 109/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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of California Davis Comprehensive Cancer CenterSacramentoCaliforniaUnited States95817

    Sponsors and Collaborators

    • University of California, Davis
    • Pharmacyclics LLC.

    Investigators

    • Principal Investigator: Primo Lara, University of California, Davis

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    University of California, Davis
    ClinicalTrials.gov Identifier:
    NCT02899078
    Other Study ID Numbers:
    • 895892
    • UCDCC#262
    • UCDCC#262
    • NCI-2016-01266
    First Posted:
    Sep 14, 2016
    Last Update Posted:
    Feb 10, 2022
    Last Verified:
    Feb 1, 2022
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleTreatment (Ibrutinib, Nivolumab)
    Arm/Group DescriptionPatients 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: Given PO Nivolumab: Given IV
    Period Title: Overall Study
    STARTED31
    COMPLETED28
    NOT COMPLETED3

    Baseline Characteristics

    Arm/Group TitleTreatment (Ibrutinib, Nivolumab)
    Arm/Group DescriptionPatients 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: Given PO Nivolumab: Given IV
    Overall Participants31
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    60
    Sex: Female, Male (Count of Participants)
    Female
    8
    25.8%
    Male
    23
    74.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    6.5%
    Not Hispanic or Latino
    29
    93.5%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    3.2%
    Asian
    2
    6.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    1
    3.2%
    White
    27
    87.1%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    31
    100%

    Outcome Measures

    1. Primary Outcome
    TitleProgression-free Survival (PFS)
    DescriptionProgression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
    Time FrameFrom baseline to death or progression, assessed for up to 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment (Ibrutinib, Nivolumab)
    Arm/Group DescriptionPatients 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: Given PO Nivolumab: Given IV
    Measure Participants28
    Median (95% Confidence Interval) [months]
    2.5
    2. Secondary Outcome
    TitleNational Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03
    DescriptionNumber of participants with adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
    Time FrameUp to 30 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment (Ibrutinib, Nivolumab)
    Arm/Group DescriptionPatients 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: Given PO Nivolumab: Given IV
    Measure Participants31
    Number [participants]
    31
    100%
    3. Secondary Outcome
    TitleOverall Survival
    DescriptionOverall survival, calculated using the Kaplan-Meier method as the duration from start of treatment to death by any cause.
    Time FrameUp to 32 months.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment (Ibrutinib, Nivolumab)
    Arm/Group DescriptionPatients 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: Given PO Nivolumab: Given IV
    Measure Participants28
    Median (95% Confidence Interval) [months]
    9.1
    4. Secondary Outcome
    TitleResponse
    DescriptionResponse Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
    Time FrameUp to 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment (Ibrutinib, Nivolumab)
    Arm/Group DescriptionPatients 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: Given PO Nivolumab: Given IV
    Measure Participants28
    Number (95% Confidence Interval) [percentage of evaluable participants]
    10.7
    34.5%

    Adverse Events

    Time FrameAdverse events were assessed from enrollment until 30 days after last dose of study drug. All-Cause Mortality was from first dose until death, assessed up to about 28 months.
    Adverse Event Reporting Description Incidence of adverse events according to CTCAE v4.0
    Arm/Group TitleTreatment (Ibrutinib, Nivolumab)
    Arm/Group DescriptionPatients 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: Given PO Nivolumab: Given IV
    All Cause Mortality
    Treatment (Ibrutinib, Nivolumab)
    Affected / at Risk (%)# Events
    Total16/31 (51.6%)
    Serious Adverse Events
    Treatment (Ibrutinib, Nivolumab)
    Affected / at Risk (%)# Events
    Total17/31 (54.8%)
    Blood and lymphatic system disorders
    Anemia1/31 (3.2%)
    Cardiac disorders
    Pericardial effusion1/31 (3.2%)
    Gastrointestinal disorders
    Ascites1/31 (3.2%)
    Esophagitis1/1 (100%)
    Gastric hemorrhage1/1 (100%)
    Gastrointestinal disorders - Other, specify1/1 (100%)
    Nausea1/1 (100%)
    Vomiting1/31 (3.2%)
    Infections and infestations
    Urinary tract infection1/31 (3.2%)
    Infections and infestations - Other, specify1/31 (3.2%)
    Lung infection1/31 (3.2%)
    Injury, poisoning and procedural complications
    Hip fracture1/31 (3.2%)
    Investigations
    Alanine aminotransferase increased1/31 (3.2%)
    Aspartate aminotransferase increased1/31 (3.2%)
    Metabolism and nutrition disorders
    Hypercalcemia1/31 (3.2%)
    Hypokalemia1/31 (3.2%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal and connective tissue disorder - Other, specify1/31 (3.2%)
    Pain in extremity1/31 (3.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)1/31 (3.2%)
    Nervous system disorders
    Dizziness1/31 (3.2%)
    Headache1/31 (3.2%)
    Nervous system disorders - Other, specify1/31 (3.2%)
    Psychiatric disorders
    Psychiatric disorders - Other, specify1/31 (3.2%)
    Renal and urinary disorders
    Acute kidney injury2/31 (6.5%)
    Hematuria1/31 (3.2%)
    Urinary retention1/31 (3.2%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea1/31 (3.2%)
    Hypoxia1/31 (3.2%)
    Pleural effusion1/31 (3.2%)
    Vascular disorders
    Hematoma1/31 (3.2%)
    Hypotension1/31 (3.2%)
    Other (Not Including Serious) Adverse Events
    Treatment (Ibrutinib, Nivolumab)
    Affected / at Risk (%)# Events
    Total31/31 (100%)
    Blood and lymphatic system disorders
    Anemia11/31 (35.5%)
    General disorders
    Fatigue18/31 (58.1%)
    Investigations
    Lymphocyte count reduction12/31 (38.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleAnalyst
    OrganizationUniversity of California, Davis
    Phone916-734-8053
    Emailnlogihara@ucdavis.edu
    Responsible Party:
    University of California, Davis
    ClinicalTrials.gov Identifier:
    NCT02899078
    Other Study ID Numbers:
    • 895892
    • UCDCC#262
    • UCDCC#262
    • NCI-2016-01266
    First Posted:
    Sep 14, 2016
    Last Update Posted:
    Feb 10, 2022
    Last Verified:
    Feb 1, 2022