Metastatic Melanoma Clinical Trial
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
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.
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 evaluate molecular determinants of response using next generation sequencing and other sequencing techniques. 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 28 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. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT02224781 -
Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma
|
Phase 3 | |
Active, not recruiting |
NCT05470283 -
Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma
|
Phase 1 | |
Recruiting |
NCT05388877 -
E6201 and Dabrafenib for the Treatment of Central Nervous System Metastases From BRAF V600 Mutated Metastatic Melanoma
|
Phase 1 | |
Active, not recruiting |
NCT05103891 -
Relative Bioavailability of Binimetinib 3 x 15 mg and 45 mg Formulations
|
Phase 1 | |
Completed |
NCT00414765 -
Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
|
Phase 4 | |
Completed |
NCT02857270 -
A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer
|
Phase 1 | |
Completed |
NCT01621490 -
PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma
|
Phase 1 | |
Recruiting |
NCT05779423 -
Cryoablation+Ipilimumab+Nivolumab in Melanoma
|
Phase 2 | |
Active, not recruiting |
NCT04940299 -
Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma
|
Phase 2 | |
Active, not recruiting |
NCT02278887 -
Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma
|
Phase 3 | |
Active, not recruiting |
NCT02360579 -
Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma
|
Phase 2 | |
Terminated |
NCT02521870 -
A Trial of Intratumoral Injections of SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma or Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
|
Phase 1/Phase 2 | |
Completed |
NCT02177110 -
A Translational Systems Medicine Approach to Provide Predictive Capacity for Therapy Response in Advanced or Metastatic Malignant Melanoma
|
||
Withdrawn |
NCT01340729 -
Open-Label Study of TPI 287 for Patients With Metastatic Melanoma
|
Phase 1/Phase 2 | |
Withdrawn |
NCT01416844 -
Study of Immune Responses in Patients With Metastatic Melanoma
|
Phase 2 | |
Terminated |
NCT01468818 -
Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma
|
Phase 2 | |
Completed |
NCT00984464 -
Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma
|
Phase 2 | |
Completed |
NCT00631618 -
Clinical Trial of Sutent to Treat Metastatic Melanoma
|
Phase 2 | |
Terminated |
NCT00571116 -
Disulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy
|
Phase 1 | |
Recruiting |
NCT00226473 -
Standard Palliative Care Versus Standard Palliative Care Plus Polychemotherapy in Metastasized Malignant Melanoma
|
Phase 4 |