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

• ClinicalTrials.gov Identifier: NCT04581382
• Recruitment Status: Recruiting
• First Posted: October 9, 2020
• Last Update Posted: January 6, 2023
• Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Mayo Clinic

Tracking Information

• First Submitted Date: September 18, 2020
• First Posted Date: October 9, 2020
• Last Update Posted Date: January 6, 2023
• Actual Study Start Date: December 14, 2020
• Estimated Primary Completion Date: October 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2020)

• Feasibility of treatment approach [ Time Frame: 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 [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 5, 2020)

• Overall response rate [ Time Frame: 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).
• Progression-free survival (PFS) [ Time Frame: 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) [ Time Frame: From registration to death from any cause, assessed up to 2 years ]
  OS will be estimated using the method of Kaplan-Meier.
• Incidence of adverse events (AEs) [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: May 5, 2022)

• Effects of plasma exchange on immune cell function [ Time Frame: Up to 2 years ]
• Kinetics of extracellular vesicles after plasma exchange in patients with melanoma [ Time Frame: Up to 2 years ]
  Will associate the kinetics with clinical outcome data (response rate, OS, PFS).

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Radiation Therapy, Plasma Exchange, and Immunotherapy (Pembrolizumab or Nivolumab) for the Treatment of Melanoma
• Official Title: Radiation Therapy, Plasma Exchange, and Immunotherapy in Melanoma
• 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 days 4-6 or 5-7. Beginning on day 7, 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.

After completion of study treatment, patients are followed up at 3 weeks and then for up to 2 years.

• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Melanoma

Intervention

• Biological: Nivolumab
  Given IV
  Other Names:

  • BMS-936558
  • CMAB819
  • MDX-1106
  • NIVO
  • Nivolumab Biosimilar CMAB819
  • ONO-4538
  • Opdivo
• Biological: Pembrolizumab
  Given IV
  Other Names:

  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475
• Radiation: Radiation Therapy
  Undergo radiation therapy
  Other Names:

  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
• Biological: Therapeutic Exchange Plasma
  Undergo therapeutic plasma exchange
  Other Name: TEP

Study Arms

Experimental: Treatment (radiation therapy, plasma exchange, immunotherapy)

Patients undergo radiation therapy daily on days 1-5 (weekdays). Patients then undergo therapeutic plasma exchange over 1-2 hours on days 4-6 or 5-7. Beginning on day 7, 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.

Interventions:

• Biological: Nivolumab
• Biological: Pembrolizumab
• Radiation: Radiation Therapy
• Biological: Therapeutic Exchange Plasma

• Publications *: 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 15, 2021): 20
• Original Estimated Enrollment (submitted: October 5, 2020): 12
• Estimated Study Completion Date: October 31, 2024
• Estimated Primary Completion Date: October 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)
• Feasible vascular access as determined by study apheresis technician (either by peripheral intravenous access or by placement of a temporary central line)
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04581382
• Other Study ID Numbers: MC200703; NCI-2020-06970 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); MC200703 ( Other Identifier: Mayo Clinic in Rochester )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mayo Clinic
• Original Responsible Party: Same as current
• Current Study Sponsor: Mayo Clinic
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jacob J Orme; Mayo Clinic in Rochester

• PRS Account: Mayo Clinic
• Verification Date: January 2023