Melanoma
Conditions
Brief summary
This early phase I trial investigates how well radiation therapy, plasma exchange, and pembrolizumab or nivolumab work in treating patients with melanoma. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Plasma exchange (also known as plasmapheresis) is a way to clean or flush out the blood. Immunotherapy with monoclonal antibodies, such as pembrolizumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Plasma exchange may help to improve the effect of standard radiation therapy and immunotherapy treatment on tumor cells of patients with melanoma.
Detailed description
PRIMARY OBJECTIVE: I. To determine the kinetics of soluble (s)PD-L1 removal and regeneration by plasma exchange in patients with melanoma. SECONDARY OBJECTIVES: I. To observe response at 3 months after plasma exchange plus immunotherapy. II. To observe ongoing response at approximate 3 month intervals after plasma exchange plus immunotherapy. CORRELATIVE RESEARCH OBJECTIVES: I. To determine the effects of plasma exchange on immune cell function. II. To observe the kinetics of extracellular vesicles (EVs) after plasma exchange in patients with melanoma. OUTLINE: Patients undergo radiation therapy daily on days 1-5 (weekdays). Patients then undergo therapeutic plasma exchange over 1-2 hours on the first session starting on the last day of radiation therapy and the last session ending prior to immunotherapy. Beginning day 5, patients receive pembrolizumab intravenously (IV) or nivolumab IV. Treatment with pembrolizumab continues every 3 weeks or treatment with nivolumab continues every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study and standard of care (SOC) computed tomography (CT), positron emission tomography (PET), and/or magnetic resonance imaging (MRI) scans as clinically indicated during follow-up. After completion of study treatment, patients are followed up at 3 weeks and then for up to 2 years.
Interventions
BIOLOGICALNivolumab
Given IV
BIOLOGICALPembrolizumab
Given IV
RADIATIONRadiation Therapy
Undergo radiation therapy
BIOLOGICALTherapeutic Exchange Plasma
Undergo therapeutic plasma exchange
PROCEDUREBiospecimen Collection
Undergo blood sample collection
PROCEDUREComputed Tomography
Undergo CT
PROCEDUREPositron Emission Tomography
Undergo PET
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological confirmation of melanoma. Patients may have completed biopsy outside of Mayo Clinic, but there must be an internal review done to confirm diagnosis prior to confirming eligibility * Measurable or non-measurable disease * Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 3 * sPD-L1 levels \> 1.7 ng/ml by enzyme-linked immunosorbent assay (ELISA) * Negative pregnancy test done =\< 7 days prior to radiation therapy, for women of childbearing potential only * Provide written informed consent * Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) * Willing to provide blood samples for correlative research purposes
Exclusion criteria
* Persons taking a biotin supplement * sPD-L1 level \< 1.7 ng/ml by ELISA * Pregnant or nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of treatment approach | Up to 2 years | Feasibility will be assessed by being able to complete the study accrual in a reasonable time period. |
| Kinetics of soluble (s)PD-L1 removal and regeneration by plasma exchange in patients with melanoma | Up to 2 years | Graphical methods and descriptive statistics will be used to explore this endpoint. Assessed by the change in the sPD-L1 levels over time across the different timepoints of interest. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to 2 years | PFS is defined as the time from registration to the first of either disease progression or death from any cause. |
| Incidence of adverse events (AEs) | Up to 2 years | The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting. The maximum grade for each type of AE will be recorded for each patient. |
| Overall survival (OS) | Up to 2 years | OS is defined as the time from registration to death from any cause. |
| Overall response rate | Up to 2 years | Overall response rate is the proportion of patients with a tumor response (partial response or complete response at least 4 weeks apart). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Effects of plasma exchange on immune cell function | Up to 2 years | — |
| Kinetics of extracellular vesicles after plasma exchange in patients with melanoma | Up to 2 years | Will associate the kinetics with clinical outcome data (response rate, OS, PFS). |
Countries
United States
Outcome results
None listed