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

Primary Purpose

Melanoma

Status
Active
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nivolumab
Pembrolizumab
Radiation Therapy
Therapeutic Exchange Plasma
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (radiation therapy, plasma exchange, immunotherapy)

Arm Description

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.

Outcomes

Primary Outcome Measures

Feasibility of treatment approach
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
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

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).
Progression-free survival (PFS)
PFS will be estimated using the method of Kaplan-Meier.
Overall survival (OS)
OS will be estimated using the method of Kaplan-Meier.
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.

Full Information

First Posted
September 18, 2020
Last Updated
October 18, 2023
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04581382
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 14, 2020 (Actual)
Primary Completion Date
October 31, 2024 (Anticipated)
Study Completion Date
October 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (radiation therapy, plasma exchange, immunotherapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, Lambrolizumab, MK-3475, SCH 900475
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Other Intervention Name(s)
Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
Intervention Description
Undergo radiation therapy
Intervention Type
Biological
Intervention Name(s)
Therapeutic Exchange Plasma
Other Intervention Name(s)
TEP
Intervention Description
Undergo therapeutic plasma exchange
Primary Outcome Measure Information:
Title
Feasibility of treatment approach
Description
Feasibility will be assessed by being able to complete the study accrual in a reasonable time period.
Time Frame
Up to 2 years
Title
Kinetics of soluble (s)PD-L1 removal and regeneration by plasma exchange in patients with melanoma
Description
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.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Overall response rate
Description
Overall response rate is the proportion of patients with a tumor response (partial response or complete response at least 4 weeks apart).
Time Frame
Up to 2 years
Title
Progression-free survival (PFS)
Description
PFS will be estimated using the method of Kaplan-Meier.
Time Frame
From registration to the first of either disease progression or death from any cause, assessed up to 2 years
Title
Overall survival (OS)
Description
OS will be estimated using the method of Kaplan-Meier.
Time Frame
From registration to death from any cause, assessed up to 2 years
Title
Incidence of adverse events (AEs)
Description
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.
Time Frame
Up to 2 years
Other Pre-specified Outcome Measures:
Title
Effects of plasma exchange on immune cell function
Time Frame
Up to 2 years
Title
Kinetics of extracellular vesicles after plasma exchange in patients with melanoma
Description
Will associate the kinetics with clinical outcome data (response rate, OS, PFS).
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacob J Orme
Organizational Affiliation
Mayo Clinic in Rochester
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35551087
Citation
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.
Results Reference
derived

Learn more about this trial

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

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