Phase Ib/II Trial of Ibrutinib Plus Nivolumab in Patients With Previously-Treated Metastatic Renal Cell Cancer
Overview
- Phase
- Phase 1
- Intervention
- Ibrutinib
- Conditions
- Metastatic Renal Cell Cancer
- Sponsor
- University of California, Davis
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- Progression-free Survival (PFS)
- Status
- Completed
- Last Updated
- 11 months ago
Overview
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.
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.
Investigators
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
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
Arms & Interventions
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.
Intervention: Ibrutinib
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.
Intervention: Nivolumab
Outcomes
Primary Outcomes
Progression-free Survival (PFS)
Time Frame: 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 Outcomes
- Response(Up to 6 months)
- National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03(Up to 30 days)
- Overall Survival(Up to 32 months.)