Clinical trial NCT06480110: Ebastine in Combination With Docetaxel as a Treatment for Castration-resistant Metastatic Prostate Cancer
Official title: Ebastine in Combination With Docetaxel as a Treatment for Castration-resistant Metastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Castration-resistant Prostate Cancer
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Danish Cancer Society
First posted: 2024-06-28
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Changes in the profile and concentration of urinary lipids and blood lipids
timeFrame: 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 outcomes:
measure: radiologic progression-free survival
timeFrame: 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.
measure: PSA response
timeFrame: 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
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Oncology 5073, Rigshospitalet
Study officials:
affiliation: Rigshospitalet, Denmark
name: Helle Pappot, DMsc
role: PRINCIPAL_INVESTIGATOR
References: