- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05896839
Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer
A Phase 2 Study of Nivolumab and Ipilimumab in Combination With Sirolimus and Prednisone in Kidney Transplant Recipients With Selected Unresectable or Metastatic Cutaneous Cancers
Study Overview
Status
Conditions
- Metastatic Melanoma
- Unresectable Melanoma
- Clinical Stage III Cutaneous Melanoma AJCC v8
- Metastatic Merkel Cell Carcinoma
- Metastatic Skin Squamous Cell Carcinoma
- Clinical Stage IV Cutaneous Melanoma AJCC v8
- Metastatic Basal Cell Carcinoma
- Unresectable Merkel Cell Carcinoma
- Unresectable Skin Squamous Cell Carcinoma
- Unresectable Basal Cell Carcinoma
- Metastatic Carcinoma in the Skin
- Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8
- Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8
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 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
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
La Jolla, California, United States, 92093
- Recruiting
- UC San Diego Moores Cancer Center
-
Contact:
- Site Public Contact
- Phone Number: 858-822-5354
- Email: cancercto@ucsd.edu
-
Principal Investigator:
- Soo Park
-
Los Angeles, California, United States, 90033
- Recruiting
- USC / Norris Comprehensive Cancer Center
-
Contact:
- Site Public Contact
- Phone Number: 323-865-0451
-
Principal Investigator:
- Gino K. In
-
Los Angeles, California, United States, 90020
- Recruiting
- Keck Medicine of USC Koreatown
-
Contact:
- Site Public Contact
- Phone Number: 213-388-0908
-
Principal Investigator:
- Gino K. In
-
Los Angeles, California, United States, 90033
- Recruiting
- Los Angeles General Medical Center
-
Principal Investigator:
- Gino K. In
-
Contact:
- Site Public Contact
- Phone Number: 323-865-0451
- Email: uscnorrisinfo@med.usc.edu
-
-
District of Columbia
-
Washington D.C., District of Columbia, United States, 20016
- Recruiting
- Sibley Memorial Hospital
-
Contact:
- Site Public Contact
- Phone Number: 202-243-2373
- Email: jquiver1@jhmi.edu
-
Principal Investigator:
- Evan J. Lipson
-
-
Florida
-
Aventura, Florida, United States, 33180
- Recruiting
- UM Sylvester Comprehensive Cancer Center at Aventura
-
Principal Investigator:
- Jose Lutzky
-
Contact:
- Site Public Contact
- Phone Number: 954-461-2180
-
Coral Gables, Florida, United States, 33146
- Recruiting
- UM Sylvester Comprehensive Cancer Center at Coral Gables
-
Principal Investigator:
- Jose Lutzky
-
Contact:
- Site Public Contact
- Phone Number: 305-243-2647
-
Deerfield Beach, Florida, United States, 33442
- Recruiting
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
-
Principal Investigator:
- Jose Lutzky
-
Contact:
- Site Public Contact
- Phone Number: 305-243-2647
-
Miami, Florida, United States, 33136
- Recruiting
- University of Miami Miller School of Medicine-Sylvester Cancer Center
-
Principal Investigator:
- Jose Lutzky
-
Contact:
- Site Public Contact
- Phone Number: 305-243-2647
-
Miami, Florida, United States, 33176
- Recruiting
- UM Sylvester Comprehensive Cancer Center at Kendall
-
Principal Investigator:
- Jose Lutzky
-
Contact:
- Site Public Contact
- Phone Number: 305-243-2647
-
North Miami, Florida, United States, 33181
- Recruiting
- University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
-
Principal Investigator:
- Jose Lutzky
-
Contact:
- Site Public Contact
- Email: kginnity@med.miami.edu
-
Plantation, Florida, United States, 33324
- Recruiting
- UM Sylvester Comprehensive Cancer Center at Plantation
-
Principal Investigator:
- Jose Lutzky
-
Contact:
- Site Public Contact
- Phone Number: 305-243-2647
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Active, not recruiting
- Emory University Hospital/Winship Cancer Institute
-
-
Illinois
-
Chicago, Illinois, United States, 60611
- Recruiting
- Northwestern University
-
Contact:
- Site Public Contact
- Phone Number: 312-695-1301
- Email: cancer@northwestern.edu
-
Principal Investigator:
- Sunandana Chandra
-
Shiloh, Illinois, United States, 62269
- Recruiting
- Memorial Hospital East
-
Contact:
- Site Public Contact
- Phone Number: 314-747-9912
- Email: dschwab@wustl.edu
-
Principal Investigator:
- George Ansstas
-
-
Kentucky
-
Lexington, Kentucky, United States, 40536
- Recruiting
- University of Kentucky/Markey Cancer Center
-
Contact:
- Site Public Contact
- Phone Number: 859-257-3379
-
Principal Investigator:
- Ruta Arays
-
-
Maryland
-
Baltimore, Maryland, United States, 21287
- Recruiting
- Johns Hopkins University/Sidney Kimmel Cancer Center
-
Contact:
- Site Public Contact
- Phone Number: 410-955-8804
- Email: jhcccro@jhmi.edu
-
Principal Investigator:
- Evan J. Lipson
-
-
Missouri
-
City of Saint Peters, Missouri, United States, 63376
- Recruiting
- Siteman Cancer Center at Saint Peters Hospital
-
Contact:
- Site Public Contact
- Phone Number: 800-600-3606
- Email: info@siteman.wustl.edu
-
Principal Investigator:
- George Ansstas
-
Creve Coeur, Missouri, United States, 63141
- Recruiting
- Siteman Cancer Center at West County Hospital
-
Contact:
- Site Public Contact
- Phone Number: 800-600-3606
- Email: info@siteman.wustl.edu
-
Principal Investigator:
- George Ansstas
-
St Louis, Missouri, United States, 63110
- Recruiting
- Washington University School of Medicine
-
Contact:
- Site Public Contact
- Phone Number: 800-600-3606
- Email: info@siteman.wustl.edu
-
Principal Investigator:
- George Ansstas
-
St Louis, Missouri, United States, 63129
- Recruiting
- Siteman Cancer Center-South County
-
Contact:
- Site Public Contact
- Phone Number: 800-600-3606
- Email: info@siteman.wustl.edu
-
Principal Investigator:
- George Ansstas
-
St Louis, Missouri, United States, 63136
- Recruiting
- Siteman Cancer Center at Christian Hospital
-
Contact:
- Site Public Contact
- Phone Number: 800-600-3606
- Email: info@siteman.wustl.edu
-
Principal Investigator:
- George Ansstas
-
-
New York
-
Mineola, New York, United States, 11501
- Recruiting
- NYU Langone Hospital - Long Island
-
Contact:
- Site Public Contact
- Phone Number: 212-263-4432
- Email: cancertrials@nyulangone.org
-
Principal Investigator:
- Maya Dimitrova
-
New York, New York, United States, 10016
- Recruiting
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
-
Contact:
- Site Public Contact
- Email: CancerTrials@nyulangone.org
-
Principal Investigator:
- Maya Dimitrova
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15232
- Recruiting
- University of Pittsburgh Cancer Institute (UPCI)
-
Contact:
- Site Public Contact
- Phone Number: 412-647-8073
-
Principal Investigator:
- Diwakar Davar
-
-
Utah
-
Salt Lake City, Utah, United States, 84112
- Recruiting
- Huntsman Cancer Institute/University of Utah
-
Principal Investigator:
- Kathleen C. Kerrigan
-
Contact:
- Site Public Contact
- Phone Number: 888-424-2100
- Email: cancerinfo@hci.utah.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Treatment (nivolumab and ipilimumab)
See detailed description
|
Given IV
Other Names:
Undergo MRI
Other Names:
Given IV
Other Names:
Undergo blood sample collection
Other Names:
Given PO
Other Names:
Undergo CT scan
Other Names:
Given PO
Other Names:
Undergo kidney biopsy
Other Names:
Undergo tumor biopsy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Disease control without allograft loss
Time Frame: At 14 weeks
|
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).
|
At 14 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Objective response rate (ORR)
Time Frame: Up to 5 years
|
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.
|
Up to 5 years
|
|
Rate of allograft loss and rejection
Time Frame: Up to 5 years
|
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.
|
Up to 5 years
|
|
Duration of response (DOR) among patients who experience CR or PR
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
|
DOR will be summarized using the Kaplan-Meier method.
|
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)
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
|
Kaplan-Meier curves will be used to summarize PFS.
|
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
Time Frame: From the first dose of nivolumab + ipilimumab to the date of death from any cause, up to 5 years
|
Kaplan-Meier curves will be used to summarize OS.
|
From the first dose of nivolumab + ipilimumab to the date of death from any cause, up to 5 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Evan J Lipson, JHU Sidney Kimmel Comprehensive Cancer Center LAO
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Site
- Neoplasms
- Infections
- Virus Diseases
- Neoplasms by Histologic Type
- Neoplasms, Glandular and Epithelial
- Adenocarcinoma
- DNA Virus Infections
- Skin Diseases
- Carcinoma
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Tumor Virus Infections
- Nevi and Melanomas
- Skin Neoplasms
- Polyomavirus Infections
- Neoplasms, Basal Cell
- Carcinoma, Neuroendocrine
- Skin and Connective Tissue Diseases
- Melanoma
- Carcinoma, Basal Cell
- Carcinoma, Merkel Cell
- Amino Acids, Peptides, and Proteins
- Proteins
- Organic Chemicals
- Investigative Techniques
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Surgical Procedures, Operative
- Cytological Techniques
- Cytodiagnosis
- Biological Factors
- Polycyclic Compounds
- Antibodies, Monoclonal, Humanized
- Antibodies, Monoclonal
- Antibodies
- Immunoglobulins
- Immunoproteins
- Blood Proteins
- Serum Globulins
- Globulins
- Pregnadienes
- Pregnanes
- Steroids
- Fused-Ring Compounds
- Diagnostic Techniques, Surgical
- Chemistry Techniques, Analytical
- Macrolides
- Lactones
- Spectrum Analysis
- Receptors, Cell Surface
- Membrane Proteins
- Pregnadienediols
- Antigens
- Antigens, Surface
- Biomarkers
- Receptors, Immunologic
- Antigens, Differentiation, T-Lymphocyte
- Antigens, Differentiation
- Immune Checkpoint Proteins
- Costimulatory and Inhibitory T-Cell Receptors
- Nivolumab
- Ipilimumab
- Sirolimus
- Prednisone
- Biopsy
- Specimen Handling
- Magnetic Resonance Spectroscopy
- deltacortene
- prednylidene
- CTLA-4 Antigen
Other Study ID Numbers
- NCI-2023-04306 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- UM1CA186691 (U.S. NIH Grant/Contract)
- 10614 (Other Identifier: CTEP)
- ETCTN10614
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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