Trial record 4 of 5 for:
10614
Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer
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| ClinicalTrials.gov Identifier: NCT05896839 |
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Recruitment Status :
Recruiting
First Posted : June 9, 2023
Last Update Posted : May 20, 2024
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Procedure: Biopsy Procedure: Biospecimen Collection Procedure: Computed Tomography Biological: Ipilimumab Procedure: Kidney Biopsy Procedure: Magnetic Resonance Imaging Biological: Nivolumab Drug: Prednisone Drug: Sirolimus | Phase 1 Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 16 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Estimated Study Start Date : | August 11, 2024 |
| Estimated Primary Completion Date : | January 31, 2027 |
| Estimated Study Completion Date : | January 31, 2027 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Melanoma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (nivolumab and ipilimumab)
See detailed description
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Procedure: Biopsy
Undergo tumor biopsy
Other Names:
Procedure: Biospecimen Collection Undergo blood sample collection
Other Names:
Procedure: Computed Tomography Undergo CT scan
Other Names:
Biological: Ipilimumab Given IV
Other Names:
Procedure: Kidney Biopsy Undergo kidney biopsy
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Biological: Nivolumab Given IV
Other Names:
Drug: Prednisone Given PO
Other Names:
Drug: Sirolimus Given PO
Other Names:
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Primary Outcome Measures :
- 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).
Secondary Outcome Measures :
- 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.
- 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.
- 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.
- 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.
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
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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 must not have had prior treatment for their current cancer with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-LAG-3 or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways within 1 year of study enrollment. Prior history of adjuvant therapy is allowed if received over 1 year prior to enrollment
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05896839
Locations
| United States, California | |
| Keck Medicine of USC Koreatown | Recruiting |
| Los Angeles, California, United States, 90020 | |
| Contact: Site Public Contact 213-388-0908 | |
| Principal Investigator: Gino K. In | |
| Los Angeles General Medical Center | Recruiting |
| Los Angeles, California, United States, 90033 | |
| Contact: Site Public Contact 323-865-0451 uscnorrisinfo@med.usc.edu | |
| Principal Investigator: Gino K. In | |
| USC / Norris Comprehensive Cancer Center | Recruiting |
| Los Angeles, California, United States, 90033 | |
| Contact: Site Public Contact 323-865-0451 | |
| Principal Investigator: Gino K. In | |
| United States, Illinois | |
| Northwestern University | Recruiting |
| Chicago, Illinois, United States, 60611 | |
| Contact: Site Public Contact 312-695-1301 cancer@northwestern.edu | |
| Principal Investigator: Sunandana Chandra | |
| Memorial Hospital East | Recruiting |
| Shiloh, Illinois, United States, 62269 | |
| Contact: Site Public Contact 314-747-9912 dschwab@wustl.edu | |
| Principal Investigator: George Ansstas | |
| United States, Maryland | |
| JHU Sidney Kimmel Comprehensive Cancer Center LAO | Recruiting |
| Baltimore, Maryland, United States, 21231 | |
| Contact: Evan J. Lipson 410-502-5977 evanlipson@jhmi.edu | |
| Principal Investigator: Evan J. Lipson | |
| Johns Hopkins University/Sidney Kimmel Cancer Center | Recruiting |
| Baltimore, Maryland, United States, 21287 | |
| Contact: Site Public Contact 410-955-8804 jhcccro@jhmi.edu | |
| Principal Investigator: Evan J. Lipson | |
| United States, Missouri | |
| Siteman Cancer Center at West County Hospital | Recruiting |
| Creve Coeur, Missouri, United States, 63141 | |
| Contact: Site Public Contact 800-600-3606 info@siteman.wustl.edu | |
| Principal Investigator: George Ansstas | |
| Washington University School of Medicine | Recruiting |
| Saint Louis, Missouri, United States, 63110 | |
| Contact: Site Public Contact 800-600-3606 info@siteman.wustl.edu | |
| Principal Investigator: George Ansstas | |
| Siteman Cancer Center-South County | Recruiting |
| Saint Louis, Missouri, United States, 63129 | |
| Contact: Site Public Contact 800-600-3606 info@siteman.wustl.edu | |
| Principal Investigator: George Ansstas | |
| Siteman Cancer Center at Christian Hospital | Recruiting |
| Saint Louis, Missouri, United States, 63136 | |
| Contact: Site Public Contact 800-600-3606 info@siteman.wustl.edu | |
| Principal Investigator: George Ansstas | |
| Siteman Cancer Center at Saint Peters Hospital | Recruiting |
| Saint Peters, Missouri, United States, 63376 | |
| Contact: Site Public Contact 800-600-3606 info@siteman.wustl.edu | |
| Principal Investigator: George Ansstas | |
| United States, New York | |
| NYU Langone Hospital - Long Island | Recruiting |
| Mineola, New York, United States, 11501 | |
| Contact: Site Public Contact 212-263-4432 cancertrials@nyulangone.org | |
| Principal Investigator: Maya Dimitrova | |
| Laura and Isaac Perlmutter Cancer Center at NYU Langone | Recruiting |
| New York, New York, United States, 10016 | |
| Contact: Site Public Contact CancerTrials@nyulangone.org | |
| Principal Investigator: Maya Dimitrova | |
| United States, Pennsylvania | |
| University of Pittsburgh Cancer Institute (UPCI) | Recruiting |
| Pittsburgh, Pennsylvania, United States, 15232 | |
| Contact: Site Public Contact 412-647-8073 | |
| Principal Investigator: Diwakar Davar | |
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Evan J Lipson | JHU Sidney Kimmel Comprehensive Cancer Center LAO |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT05896839 |
| Other Study ID Numbers: |
NCI-2023-04306 NCI-2023-04306 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 10614 ( Other Identifier: JHU Sidney Kimmel Comprehensive Cancer Center LAO ) 10614 ( Other Identifier: CTEP ) UM1CA186691 ( U.S. NIH Grant/Contract ) |
| First Posted: | June 9, 2023 Key Record Dates |
| Last Update Posted: | May 20, 2024 |
| Last Verified: | December 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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. |
| URL: | https://grants.nih.gov/policy/sharing.htm |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell Carcinoma Melanoma Carcinoma, Squamous Cell Carcinoma, Basal Cell Melanoma, Cutaneous Malignant Skin Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Nevi and Melanomas |
Neoplasms by Site Skin Diseases Neoplasms, Squamous Cell Neoplasms, Basal Cell Polyomavirus Infections DNA Virus Infections Virus Diseases Infections Tumor Virus Infections Carcinoma, Neuroendocrine Adenocarcinoma Sirolimus Prednisone Cortisone Nivolumab |