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Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers

Primary Purpose

Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III Merkel Cell Carcinoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ipilimumab
Nivolumab
Prednisone
Tacrolimus
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clinical Stage III Cutaneous Melanoma AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Moffitt Cancer Center - McKinley Campus
  • Moffitt Cancer Center
  • Northwestern University
  • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Brigham and Women's Hospital
  • Dana-Farber Cancer Institute
  • University of Pittsburgh Cancer Institute (UPCI)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (tacrolimus, prednisone, nivolumab, ipilimumab)

Arm Description

Patients receive tacrolimus PO BID and prednisone PO QD. Within 28 days, patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks for up to 24 cycles (96 weeks) in the absence of disease progression or unacceptable toxicity. Patients who experience PD or patients who have experienced allograft loss at 16 weeks receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Patients also receive tacrolimus PO BID and prednisone PO QD. Cycles repeat every 3 weeks for 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Starting 6 weeks later, patients receive nivolumab IV over 30 minutes every 4 weeks for up to 21 cycles (84 weeks) in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Number (and Percentage) of Outcome Responses After Receiving Nivolumab, Tacrolimus, and Prednisone
Percentage of kidney transplant recipients who experienced complete response (CR), partial response (PR) or stable disease (SD) without allograft loss.

Secondary Outcome Measures

Objective Response (CR or PR) Rate (ORR) After Receiving Nivolumab, Tacrolimus, and Prednisone
Number (and percentage) of patients with a complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria after receiving at least one dose of nivolumab.
Rate of Allograft Loss After Receiving Nivolumab, Tacrolimus, and Prednisone
Number of subjects who experienced allograft loss after receiving at least one dose of nivolumab.
Duration of Progression-free Survival After Receiving Nivolumab, Tacrolimus, and Prednisone
From the first dose of nivolumab to the date of the first documented tumor progression or death due to any cause, whichever occurs first.
Duration of Overall Survival After Receiving Nivolumab, Tacrolimus, and Prednisone
The time from the participant's first dose of nivolumab to the date of death from any cause.
Overall Response Rate (ORR) in Patients After Receiving Ipilimumab, Nivolumab, Tacrolimus, and Prednisone
The number of participants with a CR or PR response after receiving ipilimumab, nivolumab, tacrolimus, and prednisone.
Rate of Allograft Loss After Receiving Ipilimumab, Nivolumab, Tacrolimus, and Prednisone
Number of patients who experienced allograft loss after receiving nivolumab, ipilimumab, tacrolimus, and prednisone.

Full Information

First Posted
January 24, 2019
Last Updated
October 24, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03816332
Brief Title
Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers
Official Title
Immune Checkpoint Blockade for Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 8, 2019 (Actual)
Primary Completion Date
October 11, 2022 (Actual)
Study Completion Date
September 22, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed Description
PRIMARY OBJECTIVE: I. To estimate the percent of kidney transplant recipients with selected advanced cancers for whom standard therapies would be insufficient who, 16 weeks after administration of prednisone, tacrolimus, and nivolumab, experience complete response (CR), partial response (PR), or stable disease (SD) without allograft loss. SECONDARY OBJECTIVES: 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. II. To estimate the ORR and rate of allograft loss in patients who experience progressive disease (PD) after administration of nivolumab and 1) receive ipilimumab and nivolumab, or 2) decrease or discontinue immunosuppression. EXPLORATORY OBJECTIVES: I. To characterize correlates of the host immune response, possibly 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. Changes in donor-derived cell-free deoxyribonucleic acid (DNA) (dd-cfDNA) as a marker for allograft rejection. Id. Characteristics of anti-programmed death-1 (PD-1)-associated immune-mediated adverse reactions (IMAR) in this patient population treated with immunosuppression. OUTLINE: Patients receive tacrolimus orally (PO) twice daily (BID) and prednisone PO once daily (QD). Within 28 days, patients then receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 4 weeks for up to 24 cycles (96 weeks) in the absence of disease progression or unacceptable toxicity. Patients who experience progressive disease (PD) or patients who have experienced allograft loss at 16 weeks receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Patients also receive tacrolimus PO BID and prednisone PO QD. Cycles repeat every 3 weeks for 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Starting 6 weeks later, patients receive nivolumab IV over 30 minutes every 4 weeks for up to 21 cycles (84 weeks) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 90 days, every 8 weeks for year 1, every 12 weeks for year 2, every 16 weeks for year 3, then every 24 weeks for year 4. Patients with PD are followed up every 12 weeks for up to 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III Merkel Cell Carcinoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Clinical Stage IV 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 Merkel Cell Carcinoma AJCC v8, Pathologic Stage IIIA Cutaneous Melanoma AJCC v8, Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8, Pathologic Stage IIIB Cutaneous Melanoma AJCC v8, Pathologic Stage IIIB 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 Merkel Cell Carcinoma AJCC v8, Unresectable Basal Cell Carcinoma, Unresectable Melanoma, Unresectable Merkel Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (tacrolimus, prednisone, nivolumab, ipilimumab)
Arm Type
Experimental
Arm Description
Patients receive tacrolimus PO BID and prednisone PO QD. Within 28 days, patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks for up to 24 cycles (96 weeks) in the absence of disease progression or unacceptable toxicity. Patients who experience PD or patients who have experienced allograft loss at 16 weeks receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Patients also receive tacrolimus PO BID and prednisone PO QD. Cycles repeat every 3 weeks for 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Starting 6 weeks later, patients receive nivolumab IV over 30 minutes every 4 weeks for up to 21 cycles (84 weeks) in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
ABP 206, BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
.delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
FK 506, FK-506, Fujimycin, Hecoria, Prograf, Protopic, Tacforius
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Number (and Percentage) of Outcome Responses After Receiving Nivolumab, Tacrolimus, and Prednisone
Description
Percentage of kidney transplant recipients who experienced complete response (CR), partial response (PR) or stable disease (SD) without allograft loss.
Time Frame
At 16 weeks
Secondary Outcome Measure Information:
Title
Objective Response (CR or PR) Rate (ORR) After Receiving Nivolumab, Tacrolimus, and Prednisone
Description
Number (and percentage) of patients with a complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria after receiving at least one dose of nivolumab.
Time Frame
Up to 4 months
Title
Rate of Allograft Loss After Receiving Nivolumab, Tacrolimus, and Prednisone
Description
Number of subjects who experienced allograft loss after receiving at least one dose of nivolumab.
Time Frame
Up to 4 months
Title
Duration of Progression-free Survival After Receiving Nivolumab, Tacrolimus, and Prednisone
Description
From the first dose of nivolumab to the date of the first documented tumor progression or death due to any cause, whichever occurs first.
Time Frame
Up to 4 months
Title
Duration of Overall Survival After Receiving Nivolumab, Tacrolimus, and Prednisone
Description
The time from the participant's first dose of nivolumab to the date of death from any cause.
Time Frame
Up to 3 years
Title
Overall Response Rate (ORR) in Patients After Receiving Ipilimumab, Nivolumab, Tacrolimus, and Prednisone
Description
The number of participants with a CR or PR response after receiving ipilimumab, nivolumab, tacrolimus, and prednisone.
Time Frame
Up to 3 years
Title
Rate of Allograft Loss After Receiving Ipilimumab, Nivolumab, Tacrolimus, and Prednisone
Description
Number of patients who experienced allograft loss after receiving nivolumab, ipilimumab, tacrolimus, and prednisone.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Evan J Lipson
Organizational Affiliation
JHU Sidney Kimmel Comprehensive Cancer Center LAO
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moffitt Cancer Center - McKinley Campus
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Johns Hopkins University/Sidney Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Pittsburgh Cancer Institute (UPCI)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
IPD Sharing URL
https://grants.nih.gov/policy/sharing.htm
Citations:
PubMed Identifier
32503950
Citation
Trager MH, Coley SM, Dube G, Khan S, Ingham M, Samie FH, Geskin LJ, McDonnell D, Brouder D, Saenger Y, Carvajal R. Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients. J Immunother Cancer. 2020 Jun;8(1):e000908. doi: 10.1136/jitc-2020-000908. Erratum In: J Immunother Cancer. 2021 Jan;9(1):
Results Reference
derived

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Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers

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