Radiation Therapy, Plasma Exchange, and Immunotherapy (Pembrolizumab or Nivolumab) for the Treatment of Melanoma

Early Phase 1

Active, not recruiting

• Conditions: Melanoma
• Interventions: Biological: Nivolumab; Biological: Pembrolizumab; Radiation: Radiation Therapy; Biological: Therapeutic Exchange Plasma; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Magnetic Resonance Imaging

• Registration Number: NCT04581382
• Lead Sponsor: Mayo Clinic

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.

Study Timeline

• Study First Submitted: 2020-09-18
• Study First Submitted QC: 2020-10-05
• Study First Posted: 2020-10-09
• Study Start: 2020-12-14
• Primary Completion: 2023-11-01
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-26
• Last Update Posted: 2024-04-29
• Study Completion: 2024-10-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 18

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (radiation therapy, plasma exchange, immunotherapy)	Pembrolizumab	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 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 SOC CT, PET, and/or MRI scans as clinically indicated during follow-up.
Treatment (radiation therapy, plasma exchange, immunotherapy)	Magnetic Resonance Imaging	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 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 SOC CT, PET, and/or MRI scans as clinically indicated during follow-up.
Treatment (radiation therapy, plasma exchange, immunotherapy)	Biospecimen Collection	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 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 SOC CT, PET, and/or MRI scans as clinically indicated during follow-up.
Treatment (radiation therapy, plasma exchange, immunotherapy)	Nivolumab	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 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 SOC CT, PET, and/or MRI scans as clinically indicated during follow-up.
Treatment (radiation therapy, plasma exchange, immunotherapy)	Therapeutic Exchange Plasma	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 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 SOC CT, PET, and/or MRI scans as clinically indicated during follow-up.
Treatment (radiation therapy, plasma exchange, immunotherapy)	Radiation Therapy	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 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 SOC CT, PET, and/or MRI scans as clinically indicated during follow-up.
Treatment (radiation therapy, plasma exchange, immunotherapy)	Computed Tomography	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 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 SOC CT, PET, and/or MRI scans as clinically indicated during follow-up.
Treatment (radiation therapy, plasma exchange, immunotherapy)	Positron Emission Tomography	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 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 SOC CT, PET, and/or MRI scans as clinically indicated during follow-up.

Primary Outcome Measures

Name	Time	Method
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. The Wilcoxon Signed-Rank test will be used to assess the change in the sPD-L1 levels over time across the different timepoints of interest.

Secondary Outcome Measures

Name	Time	Method
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).
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 version 5.0 will be utilized for AE reporting. The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine AE patterns.
Progression-free survival (PFS)	From registration to the first of either disease progression or death from any cause, assessed up to 2 years	PFS will be estimated using the method of Kaplan-Meier.
Overall survival (OS)	From registration to death from any cause, assessed up to 2 years	OS will be estimated using the method of Kaplan-Meier.

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States