Clinical trial NCT04581382: 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
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Melanoma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-10-09
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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.

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)
* 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

Primary outcomes:
measure: Feasibility of treatment approach
timeFrame: Up to 2 years
measure: Kinetics of soluble (s)PD-L1 removal and regeneration by plasma exchange in patients with melanoma
timeFrame: Up to 2 years
Secondary outcomes:
measure: Overall response rate
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: From registration to the first of either disease progression or death from any cause, assessed up to 2 years
measure: Overall survival (OS)
timeFrame: From registration to death from any cause, assessed up to 2 years
measure: Incidence of adverse events (AEs)
timeFrame: Up to 2 years
Other outcomes:
measure: Effects of plasma exchange on immune cell function
timeFrame: Up to 2 years
measure: Kinetics of extracellular vesicles after plasma exchange in patients with melanoma
timeFrame: Up to 2 years
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic in Rochester
name: Sean S. Park, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic in Rochester
name: Jacob J. Orme, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.