Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04581382
Recruitment Status : Recruiting
First Posted : October 9, 2020
Last Update Posted : June 21, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE September 18, 2020
First Posted Date  ICMJE October 9, 2020
Last Update Posted Date June 21, 2021
Actual Study Start Date  ICMJE December 15, 2020
Estimated Primary Completion Date October 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2021)
  • Feasibility of treatment approach [ Time Frame: Up to 2 years ]
    Feasibility will be assessed tracking of the accrual and accrual rate. This will be tracked by spreadsheet and 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  ICMJE
 (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.
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 15, 2021)
  • Effects of plasma exchange on immune cell function [ Time Frame: Up to 2 years ]
    Associate the plasma exchange on immune cell function using Fisher exact tests.
  • 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 of response rate.
  • 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 of Overall Survival.
  • 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 of PFS.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Radiation Therapy, Plasma Exchange, and Immunotherapy (Pembrolizumab or Nivolumab) for the Treatment of Melanoma
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE
  • 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  ICMJE 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 * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 15, 2021)
20
Original Estimated Enrollment  ICMJE
 (submitted: October 5, 2020)
12
Estimated Study Completion Date  ICMJE October 31, 2023
Estimated Primary Completion Date October 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • 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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04581382
Other Study ID Numbers  ICMJE MC200703
NCI-2020-06970 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC200703 ( Other Identifier: Mayo Clinic in Rochester )
P30CA015083 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
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  ICMJE Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Jacob J Orme Mayo Clinic in Rochester
PRS Account Mayo Clinic
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP