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.
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
