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

NCT04581382 | Completed Early Phase 1 DMC FDA Drug

• 4 other identifiers: MC200703NCI-2020-06970R21CA25923620-003367
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (2)

• 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

• 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. Assessed by the change in the sPD-L1 levels over time across the different timepoints of interest.

  Up to 2 years

Secondary Outcomes (4)

• Overall response rate

  Up to 2 years

• Progression-free survival (PFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Incidence of adverse events (AEs)

  Up to 2 years

Other Outcomes (2)

• 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

Study Arms (1)

Treatment (radiation therapy, plasma exchange, immunotherapy)

EXPERIMENTAL

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.

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

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (radiation therapy, plasma exchange, immunotherapy)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (radiation therapy, plasma exchange, immunotherapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (radiation therapy, plasma exchange, immunotherapy)

Therapeutic Exchange Plasma BIOLOGICAL

Undergo therapeutic plasma exchange

Also known as: TEP

Treatment (radiation therapy, plasma exchange, immunotherapy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (radiation therapy, plasma exchange, immunotherapy)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, computerized axial tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT SCAN, tomography

Treatment (radiation therapy, plasma exchange, immunotherapy)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), positron emission tomography scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (radiation therapy, plasma exchange, immunotherapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRS Scan, MRIs, NMR Imaging, NMRI, nuclear magnetic resonance imaging, sMRI, Structural MRI

Treatment (radiation therapy, plasma exchange, immunotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Davidson TM, Foster N, Lucien F, Markovic S, Dong H, Winters JL, Park SS, Orme JJ. Rescuing Cancer Immunity by Plasma Exchange in Metastatic Melanoma (ReCIPE-M1): protocol for a single-institution, open-label safety trial of plasma exchange to clear sPD-L1 for immunotherapy. BMJ Open. 2022 May 12;12(5):e050112. doi: 10.1136/bmjopen-2021-050112.

  PMID: 35551087 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; pembrolizumab; Radiotherapy; Radiation; tetraethylpyrazine; Specimen Handling; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Physical Phenomena; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Sean S. Park, M.D., Ph.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

• Jacob J. Orme, M.D., Ph.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: October 9, 2020
• Study Start: December 14, 2020
• Primary Completion: October 6, 2024
• Study Completion: October 6, 2024
• Last Updated: July 10, 2025

Record last verified: 2025-07

Locations

US (1)