Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers
Condition: 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 Melanoma; Metastatic Merkel Cell Carcinoma; Metastatic Skin Squamous Cell Carcinoma; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Cutaneous Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8; Unresectable Basal Cell Carcinoma; Unresectable Melanoma; Unresectable Merkel Cell Carcinoma
MeSH terms: Carcinoma, Merkel Cell; Carcinoma; Melanoma; Neoplasm Metastasis; Carcinoma, Basal Cell; Skin Neoplasms
Intervention: Ipilimumab; Nivolumab; Prednisone; Tacrolimus
Intervention description: Given IV; Given IV; Given PO; Given PO
Intervention MeSH terms: Prednisone; Cortisone; Nivolumab; Ipilimumab; Tacrolimus
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase I trial studies how well tacrolimus, nivolumab, and ipilimumab work in treating
      kidney transplant recipients with cancer that cannot be removed by surgery (unresectable) or
      has spread to other places in the body (metastatic). Tacrolimus may stop the growth of tumor
      cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal
      antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the
      cancer, and may interfere with the ability of tumor cells to grow and spread. Giving
      tacrolimus, nivolumab, and ipilimumab may work better in treating kidney transplant
      recipients with cancer compared to chemotherapy, surgery, radiation therapy, or targeted
      therapies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be kidney transplant recipients with a functioning allograft who do not
             currently require dialysis

          -  Patients must have histologically or cytologically confirmed melanoma, basal cell
             carcinoma, Merkel cell carcinoma, cutaneous squamous cell carcinoma, or microsatellite
             instability (MSI)-high cancers for which standard non-immunological medical, surgical,
             or radiation therapy would be insufficient (i.e., patients who are not surgical
             candidates). This trial is not intended to provide therapy as a neoadjuvant approach

          -  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 computed tomography
             (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam is
             preferred, but not required. Patients with evaluable disease but no target lesions
             (e.g., evaluable bone metastases) may be included after discussion with the principal
             investigator (PI)

          -  Patients must have documentation, in consultation with the PI, that they received,
             refused, or were ineligible for the following non-immunologic therapies:

               -  For patients with:

                    -  BRAF-mutant melanoma: prior therapies include BRAF/MEK inhibitors

                    -  Merkel cell carcinoma: prior therapies include platinum + VP-16

                    -  Basal cell carcinoma: prior therapies include Hedgehog pathway inhibitors

                    -  Cutaneous squamous cell carcinoma: prior therapies include cetuximab

                    -  MSI colorectal carcinoma: prior therapies include: leucovorin calcium,
                       5-fluorouracil and oxaliplatin (FOLFOX)

          -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2
             (Karnofsky >= 60%)

          -  Leukocytes >= 2,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional ULN

          -  Serum creatinine =< 3 x ULN

               -  Note: patients with creatinine levels above 3 x ULN may be eligible after
                  consultation with the study PI

          -  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 child-bearing potential (WOCBP) and men must agree to use
             adequate contraception (e.g., hormonal or barrier methods of birth control, or
             abstinence) prior to study entry, for the duration of study participation, and for 31
             weeks after the last dose of nivolumab or ipilimumab. 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. Men who receive nivolumab
             or ipilimumab and are sexually active with WOCBP must use a contraceptive method with
             a failure rate of < 1% per year for the duration of the study and for a period of 7
             months after the last dose of nivolumab or ipilimumab. 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

          -  Patients must be able to understand and be willing to sign a written informed consent
             document

        Exclusion Criteria:

          -  Patients must not have received a liver, lung, heart, or pancreas transplant; or
             allogeneic stem cell transplant; or any kind of bone marrow transplant

          -  Patients must not be unwilling or unable to undergo dialysis

          -  Patients must not have prior evidence of human leukocyte antigen (HLA) or non-HLA
             donor-specific antibodies (DSA). Patients with detectable DSA but negative dd-cfDNA
             may be eligible after consultation with the study PI

          -  Patients must not have a history of antibody- or cell-mediated allograft rejection
             within 3 months of study entry

          -  Patients must not have had chemotherapy or radiotherapy within 4 weeks of study entry
             or those who have not recovered from adverse events (AEs) due to agents administered
             more than 4 weeks earlier

          -  Patients must not have had prior treatment for their current cancer with an anti-PD-1,
             anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug
             specifically targeting T-cell co-stimulation or immune checkpoint pathways

          -  Patients must not be receiving any other investigational agents

          -  Patients must not have known central nervous system (CNS) metastases or leptomeningeal
             metastases because of poor prognosis and concerns regarding progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other AEs. Patients
             with brain metastases are permitted to enroll if metastases have been treated and
             there is no MRI evidence of progression for 4 weeks after treatment is complete and no
             evidence of progression within 28 days prior to study entry

          -  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 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 psychiatric illness/social situations that would
             limit compliance with study requirements

          -  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 must not have active autoimmune disease, or history of autoimmune disease
             that might recur, which may affect vital organ function, and will only be eligible
             after consultation with the study PI

               -  This includes but is not limited to:

                    -  Immune-related neurologic disease,

                    -  Multiple sclerosis,

                    -  Autoimmune (demyelinating) neuropathy,

                    -  Guillain-Barre (GB) syndrome,

                    -  Myasthenia gravis,

                    -  Systemic autoimmune diseases such as systemic lupus erythematosus (SLE),

                    -  Connective tissue diseases,

                    -  Scleroderma,

                    -  Inflammatory bowel disease (IBD; e.g., ulcerative colitis or Crohn's
                       disease),

                    -  Rheumatoid arthritis, and

                    -  Sjogren's syndrome

          -  Patients must not have had evidence of active or acute diverticulitis, intra-abdominal
             abscess, gastrointestinal (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