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

NCT06931119 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: 0173-25-RMC
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Pruritus

Keywords

pruritus, immune checkpoint inhibitors

Outcome Measures

Primary Outcomes (1)

• Response is defined as 6 points reduction of pruritus intensity compared to the baseline value.

  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 Outcomes (1)

• Duration of pruritus relieving: the time from pruritus effective relief to 12-PSS score increase

  baseline and up to 12 weeks post treatment

Study Arms (1)

1 cycle of EMEND® capsules administration

EXPERIMENTAL

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.

Interventions

EMEND® (EE mend) (aprepitant) capsules (80mg +125mg) Marketing Authorization Holder and Importer: Merck Sharp & Dohme (Israel-1996) Company Ltd. DRUG

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

1 cycle of EMEND® capsules administration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rabin Medical Center: lead

MeSH Terms

Conditions

Pruritus

Interventions

Aprepitant; Capsules

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

Gal Markel Director of Davidoff cancer center, deputy CEO RMC, Professor

CONTACT

972-3-937-7990; galma4@clalit.org.il

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Davidoff cancer center, Deputy CEO Rabin medical center

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: April 17, 2025
• Study Start: May 30, 2025
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: April 17, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share