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

Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

For patients with BRAF-mutant melanoma, prior therapies include BRAF/MEK inhibitors

For patients with Basal cell carcinoma, prior therapies include hedgehog pathway inhibitors

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • Biopsy Procedure

    Procedure/Surgery

    Undergo tumor biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo CT scan

  • Ipilimumab

    Biological/Vaccine

    Given IV

  • Kidney Biopsy

    Procedure/Surgery

    Undergo kidney biopsy

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Nivolumab

    Biological/Vaccine

    Given IV

  • Prednisone

    Drug

    Given PO

  • Sirolimus

    Drug

    Given PO

Treatment groups

16 Participants
are divided into 1 treatment group
Group A: Treatment (nivolumab and ipilimumab)Experimental treatment 9 interventions

Trial outcomes

Primary outcomes

1

Disease control without allograft loss

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).

Time frame
At 14 weeks

Secondary outcomes

1

Objective response rate (ORR)

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.

Time frame
Up to 5 years
2

Rate of allograft loss and rejection

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.

Time frame
Up to 5 years
3

Duration of response (DOR) among patients who experience CR or PR

DOR will be summarized using the Kaplan-Meier method.

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
4

Progression-free survival (PFS)

Kaplan-Meier curves will be used to summarize 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

Other outcomes

Sponsors and contacts

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