Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer

Recruiting now · Phase 1/Phase 2

Conditions studied: Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8, Metastatic Basal Cell Carcinoma, Metastatic Carcinoma in the Skin, Metastatic Melanoma, Metastatic Merkel Cell Carcinoma, Metastatic Skin Squamous Cell Carcinoma, Unresectable Basal Cell Carcinoma, Unresectable Melanoma, Unresectable Merkel Cell Carcinoma, Unresectable Skin Squamous Cell Carcinoma

In brief

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.

Key facts

Study ID: NCT05896839
Run by: National Cancer Institute (NCI)
People needed: 16
Starts: 2024-07-24
Expected to finish: 2027-01-31
Last updated by the study team: 2026-07-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients must be kidney transplant recipients with a functioning allograft who do not currently require dialysis
Patient's age must be >= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of nivolumab and ipilimumab in kidney transplant recipients <18 years of age, children are excluded from this study, but may be eligible for future pediatric trials
Patients must have histologically or cytologically confirmed non-uveal melanoma, basal cell carcinoma, Merkel cell carcinoma, or cutaneous squamous cell carcinoma for which standard non-immunological medical, surgical, or radiation therapy would be insufficient (i.e., patients who are not surgical candidates). Patients with cutaneous squamous cell carcinoma or Merkel cell carcinoma may enroll without prior medical therapy (e.g., cetuximab or chemotherapy respectively). Non-immunologic standard therapies that patients must have received, refused or for which patients were ineligible include:
For patients with BRAF-mutant melanoma, prior therapies include BRAF/MEK inhibitors
For patients with Basal cell carcinoma, prior therapies include hedgehog pathway inhibitors
Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, i.e., at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm by chest x-ray or as >= 10 mm with CT scan, magnetic resonance imaging (MRI), or calipers by clinical exam is preferred, but not required
Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) performance status criteria
Leukocytes >= 2,000/mcL
Absolute neutrophil count >= 1,500/mcL
Platelets >= 50,000/mcL
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional ULN
Serum creatinine =< 3 x ULN
dd-cfDNA =< 1.0% and =< 61% increase
The effects of nivolumab and ipilimumab on the developing human fetus are unknown. For this reason, and because other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential (WOCBP) receiving nivolumab must continue contraception for a period of 5 months after the last dose of nivolumab. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin [B-HCG]) during the screening period. Follow-up evaluations will include interval sexual/menstrual histories as needed.
Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately.
WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. Women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL to be considered postmenopausal.
Human immunodeficiency virus (HIV)-infected patients will be eligible for this trial if they are on effective antiretroviral regimens utilizing non-CYP-interactive agents and have an undetectable viral load. If there is evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy, if indicated. If there is history of hepatitis C virus (HCV) infection, the patient must have been treated and have undetectable HCV viral load.
Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

You may not qualify if…

Patients who have received a liver, lung, heart, or pancreas transplant; or allogeneic stem cell transplant; or any kind of bone marrow transplant
Patients unwilling or unable to undergo dialysis in the event of allograft failure
Patients with prior evidence of human leukocyte antigen (HLA) or non-HLA donor-specific antibodies (DSA)
Patients with a history of antibody- or cell-mediated allograft rejection within 3 months of study entry
Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment
Patients may have received prior anti-PD-(L)1 therapy; however, patients must not have any other checkpoint antibody targeting T-cell co-stimulation within 1 year of study enrollment. Prior history of adjuvant therapy is allowed if received over 1 year prior to enrollment. Prior receipt of oncolytic therapy (e.g., TVEC, RP1) is allowed
Patients must not be receiving any other investigational agents
Patients with leptomeningeal metastases, more than 3 untreated central nervous system (CNS) metastases, untreated brain metastases measuring >1cm, or requiring treatment-dose steroids (> 10 mg/day prednisone equivalents) for CNS-related symptoms. Exclusions are due to concerns regarding progressive neurologic dysfunction that would confound the evaluation of neurologic and other AEs. Patients with brain metastases meeting the above requirements are permitted to enroll
Patients must not have a history of severe hypersensitivity reaction to any monoclonal antibody
Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in the study
Patients must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other significant condition(s) that would make this protocol unreasonably hazardous
Pregnant women are excluded from this study because nivolumab and ipilimumab have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with nivolumab or ipilimumab. These potential risks may also apply to other agents used in this study
Patients with autoimmune disease that is active or might recur and affect vital organ function will be eligible only after consultation with the study PI. Guillain-Barre (GB) syndrome, bullous skin disease, Stevens Johnson syndrome, or toxic epidermal necrolysis will be excluded
Patients must not have had evidence of active or acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study. In addition, patients with a history of cardiac disease including coronary artery disease (CAD), myocardial infarction (MI), cardiomyopathy, arrhythmia, heart block, should have an evaluation by history pulmonary embolism (PE) and appropriate testing to allow evaluation of any events that may occur on study. These may include troponin, electrocardiogram (EKG), echocardiogram (ECHO) as clinically indicated and may include results already in the medical record if available

Where it is running

Huntsman Cancer Institute/University of Utah — Salt Lake City, Utah, United States (enrolling)
Keck Medicine of USC Koreatown — Los Angeles, California, United States (enrolling)
Los Angeles General Medical Center — Los Angeles, California, United States (enrolling)
USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States (enrolling)
Sibley Memorial Hospital — Washington D.C., District of Columbia, United States (enrolling)
UM Sylvester Comprehensive Cancer Center at Aventura — Aventura, Florida, United States (enrolling)
UM Sylvester Comprehensive Cancer Center at Coral Gables — Coral Gables, Florida, United States (enrolling)
UM Sylvester Comprehensive Cancer Center at Deerfield Beach — Deerfield Beach, Florida, United States (enrolling)
University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States (enrolling)
UM Sylvester Comprehensive Cancer Center at Kendall — Miami, Florida, United States (enrolling)
University of Miami Sylvester Comprehensive Cancer Center at Sole Mia — North Miami, Florida, United States (enrolling)
UM Sylvester Comprehensive Cancer Center at Plantation — Plantation, Florida, United States (enrolling)
UC San Diego Moores Cancer Center — La Jolla, California, United States (enrolling)
Northwestern University — Chicago, Illinois, United States (enrolling)
Memorial Hospital East — Shiloh, Illinois, United States (enrolling)
University of Kentucky/Markey Cancer Center — Lexington, Kentucky, United States (enrolling)
Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States (enrolling)
Siteman Cancer Center at Saint Peters Hospital — City of Saint Peters, Missouri, United States (enrolling)
Siteman Cancer Center at West County Hospital — Creve Coeur, Missouri, United States (enrolling)
Washington University School of Medicine — St Louis, Missouri, United States (enrolling)
Siteman Cancer Center-South County — St Louis, Missouri, United States (enrolling)
Siteman Cancer Center at Christian Hospital — St Louis, Missouri, United States (enrolling)
NYU Langone Hospital - Long Island — Mineola, New York, United States (enrolling)
Laura and Isaac Perlmutter Cancer Center at NYU Langone — New York, New York, United States (enrolling)
UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (enrolling)

Full record on ClinicalTrials.gov

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