Metastatic Castration-resistant Prostate Cancer
Conditions
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.
Interventions
DRUGDocetaxel + Ebastine
Ebastine is administered once daily.
DRUGDocetaxel
docetaxel every three weeks
Sponsors
Danish Cancer Society
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the profile and concentration of urinary lipids and blood lipids | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| radiologic progression-free survival | 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. | 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. |
| PSA response | 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 | Prostate-Specific Antigen (PSA) Response criteria according to Prostate Cancer Working Group (PCWG3) 3rd edition |
Countries
Denmark
Contacts
Primary ContactHelle Pappot, DMsc
Outcome results
None listed