Aprepitant in the Management of Immune Checkpoint Inhibitors Pruritus in Solid Cancer Patients

April 8, 2025 updated by: Gal Markel, Rabin Medical Center

Aprepitant in the Management of Immune Checkpoint Inhibitors Pruritus: Pilot Study in Solid Cancer Patients

Pruritus, commonly known as itching, is an unpleasant sensation that triggers the urge to scratch, which may provide temporary relief. Pruritus can be intermittent or persistent, localized or widespread, and may be associated with medication use. Chronic pruritus, defined as lasting more than six weeks, can significantly affect sleep and quality of life.

Dermatologic toxicities are among the most common immune-related adverse events (irAEs), reported in 43-45% of patients receiving ipilimumab and approximately 34% of those treated with nivolumab or pembrolizumab. Combination therapies (ipilimumab+ nivolumab or pembrolizumab) tend to elevate the incidence of potential irAEs to 41%. These toxicities typically emerge within the first few weeks of treatment, though delayed-onset cases have been documented. Cutaneous irAEs occur more rapidly in patients receiving combination therapy compared to anti-PD1 monotherapy.

Pruritus is one of the most frequently observed cutaneous irAEs. Current treatments for pruritus are often inadequate, leaving many patients suffering from persistent and debilitating symptoms. Despite available therapies, a significant number of individuals continue to experience chronic itch that negatively impacts their quality of life. Substance P (SP) functions as a neurotransmitter and neuromodulator in the central and peripheral nervous systems of mammals. It is produced by both neuronal and non-neuronal cells and plays a role in various physiological responses, including nausea, depression, vomiting, pain, neurogenic inflammation, and, more recently, pruritus. SP exerts its biological effects primarily through neurokinin receptors (NKRs), also known as tachykinin receptors. When SP binds to NK1R in the skin, it triggers mast cell degranulation, leading to the release of pruritogenic and proinflammatory mediators such as histamine, interferon-γ, leukotriene B4, vascular endothelial growth factor (VEGF), and nerve growth factor (NGF). This results in vasodilation and neurogenic inflammation, manifesting clinically as pruritus, erythema, and edema. NK1R antagonists are a class of drugs with antiemetic, antidepressant, anxiolytic, and antipruritic properties, though they have not been effective as analgesics in humans. These drugs act centrally by crossing the blood-brain barrier and selectively blocking NK1R activation by SP in the central nervous system, particularly in vomiting centers. Aprepitant has also demonstrated efficacy in treating pruritus induced by anticancer therapies.

This study is a pilot, single-center open label study evaluating the safety and efficacy of single course of EMEND® (aprepitant) capsules (80mg +125mg) in treating pruritus (new onset and/or refractory) induced by immune checkpoint inhibitors in patients with solid tumors.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Gal Markel Director of Davidoff cancer center, deputy CEO RMC, Professor
  • Phone Number: 972-3-937-7990
  • Email: galma4@clalit.org.il

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥18 years.
  • Histologically confirmed solid tumor (e.g., melanoma, RCC, NSCLC).
  • Currently receiving ICIs (such as but not limited to nivolumab, pembrolizumab, ipilimumab)
  • Pruritus that is either:
  • Refractory: Persistent pruritus despite standard treatment (e.g., antihistamines, corticosteroids).
  • New-onset: Developing after initiation of ICIs or targeted therapies.
  • ECOG performance status 0-2.
  • Willingness to comply with study procedures and provide informed consent.

Exclusion Criteria:

  • History of severe allergic reactions to Aprepitant.
  • Uncontrolled or severe dermatologic conditions unrelated to cancer therapy.
  • Use of NK1R antagonists within 4 weeks before study entry.
  • Concurrent use of medications that strongly interact with Aprepitant.
  • Concurrent use of medications that may influence pruritus manifestation (e.g steroids or antihistamines) . Note, Regular treatment with such medications prior to the appearance of pruritus, and or pruritus appearing despite such regular treatment, will not disqualify you from participating in the study
  • Uncontrolled infection or significant comorbidities.
  • Pregnant or breastfeeding women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1 cycle of EMEND® capsules administration

1 cycle (1 administration of EMEND® capsules)

  • Frequency: Patients will take EMEND® capsules at the start of new ICI.

  • Dosing Schedule:

    • Day 1: EMEND® 125 mg, taken orally 1-2 hours before ICI administration.
    • Day 2: EMEND® 80 mg, taken orally in the morning.
    • Day 3: EMEND® 80 mg, taken orally in the morning 7 days after the first capsule of Aprepitant- 12-PSS, safety assessment, QLQ-C30 Follow-up 2- 12-PSS, safety assessment Follow-up 3- 12-PSS, safety assessment Follow-up 4- 12-PSS, QLQ-C30, safety assessment, review of rescue medication use Extended Follow-up- Recurrence of pruritus, long-term safety monitoring, QLQ-C30
Drug: EMEND® (EE mend) (aprepitant) capsules (80mg +125mg) Marketing Authorization Holder and Importer: Merck Sharp & Dohme (Israel-1996) Company Ltd.

Total Treatment Duration: 1 cycle (1 administration of EMEND® capsules)

  • Frequency: Patients will take EMEND® capsules at the start of new ICI.

  • Dosing Schedule:

    • Day 1: EMEND® 125 mg, taken orally 1-2 hours before ICI administration.
    • Day 2: EMEND® 80 mg, taken orally in the morning.
    • Day 3: EMEND® 80 mg, taken orally in the morning. During the study period (12 weeks), participant must refrain from using any medications that could potentially interfere with the study's assessment of pruritus symptoms (e.g steroids, antihistamines)

Follow-up 1(7 days after the first capsule of Aprepitant): 12-PSS, safety assessment, QLQ-C30 Follow-up 2: 12-PSS, safety assessment Follow-up 3: 12-PSS, safety assessment Follow-up 4: 12-PSS, QLQ-C30, safety assessment Extended Follow-up: Recurrence of pruritus, long-term safety monitoring, QLQ-C30

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response is defined as 6 points reduction of pruritus intensity compared to the baseline value.
Time Frame: 12-Item Pruritus Severity Scale (12-PSS) score over a 12 weeks period, at baseline, every 7 days periprocedural for 4 weeks, and up to 12 weeks
score interpretation: mild (3-6), moderate (7-11), or severe (12-22). higher scores indicate severe pruritus.
12-Item Pruritus Severity Scale (12-PSS) score over a 12 weeks period, at baseline, every 7 days periprocedural for 4 weeks, and up to 12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Duration of pruritus relieving: the time from pruritus effective relief to 12-PSS score increase
Time Frame: baseline and up to 12 weeks post treatment
baseline and up to 12 weeks post treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rabin Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 30, 2025

Primary Completion (Estimated)

May 30, 2026

Study Completion (Estimated)

December 30, 2026

Study Registration Dates

First Submitted

April 1, 2025

First Submitted That Met QC Criteria

April 8, 2025

First Posted (Actual)

April 17, 2025

Study Record Updates

Last Update Posted (Actual)

April 17, 2025

Last Update Submitted That Met QC Criteria

April 8, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0173-25-RMC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

IPD used in the results publication

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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