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Brief Title: Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer
Official Title: A Phase 1/2 Study of Nivolumab and Ipilimumab in Combination With Sirolimus and Prednisone in Kidney Transplant Recipients With Selected Unresectable or Metastatic Cutaneous Cancers
Study ID: NCT05896839
Brief Summary: This phase I/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.
Detailed Description: 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 evaluate molecular determinants of response using next generation sequencing and other sequencing techniques. 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.. 6 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 undergo computed tomography (CT) scan at screening, at cycle 3 day 1, on day 1 of odd numbered cycles, and at follow up. Patients may undergo magnetic resonance imaging (MRI) at screening. Patients undergo tumor biopsy at cycle 1 day 8, cycle 2 day 1. Patients may undergo kidney biopsy if rejection is suspected. Patients undergo blood sample collection on cycle 1 day 8, cycle 2 day 1, at disease progression and if an immune mediated adverse reaction occurs. 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.
Minimum Age: 18 Years
Eligible Ages: ADULT, OLDER_ADULT
Sex: ALL
Healthy Volunteers: No
Keck Medicine of USC Koreatown, Los Angeles, California, United States
Los Angeles General Medical Center, Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center, Los Angeles, California, United States
Northwestern University, Chicago, Illinois, United States
Memorial Hospital East, Shiloh, Illinois, United States
JHU Sidney Kimmel Comprehensive Cancer Center LAO, Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland, United States
Siteman Cancer Center at West County Hospital, Creve Coeur, Missouri, United States
Washington University School of Medicine, Saint Louis, Missouri, United States
Siteman Cancer Center-South County, Saint Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital, Saint Louis, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital, Saint Peters, Missouri, United States
NYU Langone Hospital - Long Island, Mineola, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone, New York, New York, United States
University of Pittsburgh Cancer Institute (UPCI), Pittsburgh, Pennsylvania, United States
Name: Evan J Lipson
Affiliation: JHU Sidney Kimmel Comprehensive Cancer Center LAO
Role: PRINCIPAL_INVESTIGATOR