Ebastine in Combination With Docetaxel as a Treatment for Castration-resistant Metastatic Prostate Cancer

This is an open-label phase I/II study evaluating the addition of ebastine to docetaxel in the treatment for metastatic castration resistant prostate cancer.

Patients will be randomized in a 2:1 fashion to receive ebastine daily during and after treatment with a maximum of 10 courses of docetaxel.

The primary endpoint is change in the profile of urinary and blood lipids to indicate absorption and possible efficacy of ebastine.

Secondary endpoints include PSA response and radiologic progression free survival.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Docetaxel + Ebastine; Drug: Docetaxel

Detailed Description

The complete study protocol can be studied by contacting the authors.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Helle Pappot, DMsc; Phone Number: +4535458403; Email: helle.pappot@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Department of Oncology 5073, Rigshospitalet
    • Contact: Helle Pappot, MD, DMSc; Phone Number: 0045 35454222; Email: helle.pappot@regionh.dk
    • Principal Investigator: Helle Pappot, MD, DMSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Have a histologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate (carcinomas with pure small-cell histology or pure high grade neuroendocrine histology are excluded; neuroendocrine differentiation is allowed).

  2. Surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL equivalent to 1.7 nmol/L. For patients, currently being treated with luteinizing hormone-releasing hormone (LHRH) agonists, i.e., patients who have not undergone an orchiectomy, therapy must be continued throughout the study.

  3. Have evidence of disease progression after prior therapy for mCRPC:

Disease progression after initiation of most recent therapy is based on any of the following criteria:

• Rise in PSA: a minimum of 2 consecutive rising levels, with an interval of ≥ 1 week between each determination. The most recent screening measurement must have been ≥ 2 ng/mL
• Transaxial imaging: new or progressive soft tissue masses on CT or MRI scans as defined by RECIST 1.1

• Radionuclide bone scan: at least 2 new metastatic lesions 4. Signed informed consent obtained prior to initiation of any study-specific procedures or treatment 5. Age ≥ 18 years 6. Life expectancy ≥ 3 months 7. Performance status 0 - 1 8. Adequate organ functions

  1. Hematological: absolute neutrophil count (ANC) >1.5 x 109/L, platelet count >100 x 109/L, hemoglobin > 6,2 mmol/L
  2. Hepatic: Bilirubin within normal range, aspartate transaminase (AST) and alanine transaminase (ALT) <2.5 upper normal lever, albumin > 25 g/L

  3. Renal: creatinine clearance >30 mL/min/1.73m2

     Exclusion Criteria:

     - 1. History of significant gastric or small bowel resection, malabsorption syndrome, or other lack of integrity of the upper gastrointestinal tract that may prevent compliance with oral drug administration 2. Presence of any serious concomitant systemic disorders and/or psychiatric condition incompatible with the study (at the investigator's discretion) 3. Presence of any active infection (at the investigator's discretion). 4. Central nervous system (CNS) disease including epilepsy or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures.

     5. Concurrent use of cationic amphiphilic drugs (see appendix A) including over-the-counter medication.

     6. Use of other investigational drug 7. Allergic reaction to any of the included drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Standard docetaxel (10 cycles) plus ebastine daily	Drug: Docetaxel + Ebastine; Ebastine is administered once daily.; Other Names: Kestine (Ebastine)
Active Comparator: Comparator; Standard docetaxel (10 cycles) without ebastine	Drug: Docetaxel; docetaxel every three weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the profile and concentration of urinary lipids and blood lipids	Measurement of lipid species concentration, focusing on Bis(monoacylglycero)phosphate and lysophospholipids in urine and blood, before, during, and after treatment, compared to PSA levels, radiologic response, and control group results.	Blood+urine samples are collected at baseline, at evaluation scans (after 4th and 7th cycles), and at the end of treatment (after 10 Docetaxel cycles, upon progression before 10 cycles, or at study discontinuation). Each cycle is 21 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
radiologic progression-free survival	Radiologic progression-free survival is defined as ≥ two new lesions on an 8-week bone scan plus two additional lesions on a confirmatory scan, ≥ two new confirmed lesions on any scan ≥ 9 weeks after enrolment, and/or progression in nodes or viscera on cross-sectional imaging as defined by RECIST 1.1 (see below), or death.	By comparing with a baseline scan, the treatment effect and disease status will be evaluated with a scan after the 4th and 7th cycles, at end of treatment undtil study completion. Each cycle is 21 days. A patient will receive a maximum of 10 cycles.
PSA response	Prostate-Specific Antigen (PSA) Response criteria according to Prostate Cancer Working Group (PCWG3) 3rd edition	PSA response will be monitored during treatment, compared to radiologic response after the 4th and 7th cycles, and at treatment completion (maximum 10 cycles/progression/discontinuation). Each cycle lasts 21 days

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Danish Cancer Society
• Investigators: Principal Investigator: Helle Pappot, DMsc, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 18, 2020
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): June 28, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2025
• Last Update Submitted That Met QC Criteria: April 9, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Histamine H1 Antagonists; Docetaxel; Ebastine
• Other Study ID Numbers: Ebas0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No