Metastatic Renal Cell Cancer, Stage IV Renal Cell Cancer
Conditions
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.
Interventions
DRUGIbrutinib
Given PO
DRUGNivolumab
Given IV
Sponsors
Pharmacyclics LLC.
University of California, Davis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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/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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Ibrutinib: Given PO Nivolumab: Given IV | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | Treatment (Ibrutinib, Nivolumab) |
|---|---|
| Age, Continuous | 60 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 31 |
| other Total, other adverse events | 31 / 31 |
| serious Total, serious adverse events | 17 / 31 |
Outcome results
Primary
Progression-free Survival (PFS)
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.
Time frame: From baseline to death or progression, assessed for up to 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Ibrutinib, Nivolumab) | Progression-free Survival (PFS) | 2.5 months |
Secondary
National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03
Number of participants with adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
Time frame: Up to 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Ibrutinib, Nivolumab) | National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 | 31 participants |
Secondary
Overall Survival
Overall survival, calculated using the Kaplan-Meier method as the duration from start of treatment to death by any cause.
Time frame: Up to 32 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Ibrutinib, Nivolumab) | Overall Survival | 9.1 months |
Secondary
Response
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
Time frame: Up to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Ibrutinib, Nivolumab) | Response | 10.7 percentage of evaluable participants |