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

Melanoma Clinical Trial

Official title:

Radiation Therapy, Plasma Exchange, and Immunotherapy in Melanoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04581382
• Other study ID #: MC200703
• Secondary ID: NCI-2020-06970MC
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: December 14, 2020
• Est. completion date: October 31, 2024

Study information

• Verified date: April 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: October 31, 2024
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melanoma

Intervention

Biological:
• Nivolumab
Given IV
• Pembrolizumab
Given IV

Radiation:
• Radiation Therapy
Undergo radiation therapy

Biological:
• Therapeutic Exchange Plasma
Undergo therapeutic plasma exchange

Procedure:
• Biospecimen Collection
Undergo blood sample collection
• Computed Tomography
Undergo CT
• Positron Emission Tomography
Undergo PET
• Magnetic Resonance Imaging
Undergo MRI

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effects of plasma exchange on immune cell function		Up to 2 years
Other	Kinetics of extracellular vesicles after plasma exchange in patients with melanoma	Will associate the kinetics with clinical outcome data (response rate, OS, PFS).	Up to 2 years
Primary	Feasibility of treatment approach	Feasibility will be assessed by being able to complete the study accrual in a reasonable time period.	Up to 2 years
Primary	Kinetics of soluble (s)PD-L1 removal and regeneration by plasma exchange in patients with melanoma	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.	Up to 2 years
Secondary	Overall response rate	Overall response rate is the proportion of patients with a tumor response (partial response or complete response at least 4 weeks apart).	Up to 2 years
Secondary	Progression-free survival (PFS)	PFS will be estimated using the method of Kaplan-Meier.	From registration to the first of either disease progression or death from any cause, assessed up to 2 years
Secondary	Overall survival (OS)	OS will be estimated using the method of Kaplan-Meier.	From registration to death from any cause, assessed up to 2 years
Secondary	Incidence of adverse events (AEs)	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.	Up to 2 years