This phase II trial tests the combination of nivolumab and ipilimumab with sirolimus and prednisone for the treatment of skin (cutaneous) cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started to other places in the body (metastatic) in kidney transplant recipients. Immunotherapy with nivolumab and ipilimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Sirolimus and prednisone are immunosuppressants that are given to keep the body from rejecting the transplanted kidney. Giving nivolumab and ipilimumab in combination with sirolimus and prednisone may kill more cancer cells, while also keeping the transplanted kidney healthy, in patients with unresectable or metastatic cutaneous cancer who have received a kidney transplant.
PRIMARY OBJECTIVE: I. To evaluate the proportion of kidney transplant recipients with selected advanced cutaneous cancers who at 14 weeks after administration of prednisone, sirolimus, nivolumab, and ipilimumab experience complete response (CR), partial response (PR), or stable disease (SD) without allograft loss. SECONDARY OBJECTIVE: I. To estimate the objective response rate (ORR), rate of allograft loss, and durations of progression-free survival (PFS) and overall survival (OS) in the study population. EXPLORATORY OBJECTIVES: I. To characterize correlates of the host immune response including, but not limited to: Ia. Histopathological characteristics of allograft rejection/loss; Ib. Immunological changes in the tumor microenvironment (e.g., changes in T-cell subset populations or expression of immune checkpoint molecules) in paired biopsies obtained pre-treatment and on-treatment; Ic. Characteristics of anti-programmed death-1 (PD-1)-associated immune-mediated adverse reactions (IMARs) in this patient population treated with immunosuppression; Id. To identify upregulated immune-related genes using multiplex quantitative reverse transcription polymerase chain reaction (qRT-PCR). II. To observe whether changes in donor-derived cell-free deoxyribonucleic acid (DNA) (dd-cfDNA) as a marker for allograft rejection. III. To compare baseline patient allograft/donor characteristics, to include human leukocyte antigen (HLA) status, date of transplant, presence of donor specific antibodies, history of prior rejection, and Calculated Panel Reactive Antibodies score, in patients who experience and do not experience rejection while on this study. IV. To observe the objective response rate (ORR) of patients who achieve PR/CR or stable disease for \>= 6 months with eventual progressive disease requiring re-induction with nivolumab + ipilimumab (receive \> 4 doses of nivolumab + ipilimumab). OUTLINE: Patients receive sirolimus orally (PO) and prednisone PO daily, starting 7 days prior to cycle 1 day 1 of immunotherapy. Patients also receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes on day 8 of cycle 1 and day 1 of cycle 2. Six weeks after the first dose of nivolumab and ipilimumab, patients undergo tumor response assessment. Patients who achieve stable disease (SD), partial response (PR), or complete response (CR) receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for a total of 24 cycles in the absence of disease progression or unacceptable toxicity. Patients who had disease progression at this time or any time on trial may receive nivolumab IV and ipilimumab IV on day 1 of each cycle. Cycles repeat every 3 weeks for 2 cycles, in the absence of unacceptable toxicity. Patients are then assessed for tumor response again after 6 weeks and receive nivolumab monotherapy if they achieve SD, PR, or CR. If patients have progressive disease, they may receive nivolumab monotherapy or discontinue study treatment. Patients may undergo magnetic resonance imaging (MRI) during screening, undergo tumor biopsy on study and undergo computed tomography (CT) scan and blood sample collection throughout the study. Patients may undergo kidney biopsy if rejection is suspected. Patients follow up every 12 weeks for 1 year after stopping therapy, then every 16 weeks for the second year after stopping and then every 20 weeks for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Undergo tumor biopsy
Undergo blood sample collection
Undergo CT scan
Given IV
Undergo kidney biopsy
Undergo MRI
Given IV
Given PO
Given PO
UC San Diego Moores Cancer Center
La Jolla, California, United States
RECRUITINGKeck Medicine of USC Koreatown
Los Angeles, California, United States
SUSPENDEDLos Angeles General Medical Center
Los Angeles, California, United States
SUSPENDEDUSC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Disease control without allograft loss
Defined as complete or partial response (CR; PR) or stable disease (SD), at 14 weeks per response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The percent of kidney transplant recipients who experience CR/PR/SD at 14 weeks and do not experience allograft loss after administration of nivolumab, ipilimumab, sirolimus, and prednisone will be calculated, along with the corresponding exact 95% confidence interval (CI).
Time frame: At 14 weeks
Objective response rate (ORR)
Defined as the proportion of subjects whose best overall response from baseline is either a CR or PR, based on RECIST 1.1 criteria. ORR will be estimated along with 95% exact CI.
Time frame: Up to 5 years
Rate of allograft loss and rejection
Renal allograft rejection rate will be estimated as the proportion of subjects who experience markers of allograft rejection. Allograft loss is defined as allograft rejection leading to complete, permanent, and irreversible loss-of-function of the renal allograft.
Time frame: Up to 5 years
Duration of response (DOR) among patients who experience CR or PR
DOR will be summarized using the Kaplan-Meier method.
Time frame: From the time criteria are met for CR/PR (whichever is first recorded) until the first date that recurrent disease or PD is documented, up to 5 years
Progression-free survival (PFS)
Kaplan-Meier curves will be used to summarize PFS.
Time frame: From the first dose of nivolumab + ipilimumab to the date of the first documented tumor progression or death due to any cause, whichever occurs first, up to 5 years
Overall survival
Kaplan-Meier curves will be used to summarize OS.
Time frame: From the first dose of nivolumab + ipilimumab to the date of death from any cause, up to 5 years
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Sibley Memorial Hospital
Washington D.C., District of Columbia, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
RECRUITINGUniversity of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, United States
RECRUITING...and 16 more locations