Observational Study of Docetaxel Exposure in Metastatic Prostate Cancer Patients

Study Overview
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Brief Summary
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In this observational study, blood samples for pharmacokinetic (PK) testing will be collected from subjects with metastatic prostate cancer during their treatment with docetaxel. Plasma levels of docetaxel will be determined, and the subjects docetaxel exposure levels, determined as an area under the curve (AUC), will be retrospectively correlated with reports of toxicity, tumor response, quality of life, time to disease progression and overall survival to provide guidance on what the appropriate target range for docetaxel exposure should be for metastatic prostate cancer subjects receiving docetaxel therapy for their disease.

Official Title
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Observational Study of Metastatic Prostate Cancer Subjects Receiving Docetaxel Therapy for Evaluation of Docetaxel Plasma Levels Using the MyDocetaxel Assay

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: docetaxel
* Other: Blood draws


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate. Male subjects 18 years of age or older. About to start a new line of treatment with docetaxel (75 mg/m2) in combination with prednisone. All subjects must be informed of the investigational nature of this study and be willing to provide written informed consent in accordance with Institutional guidelines and good clinical practices (GCP) indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study prior to the beginning of specific study procedures. Prior surgical castration or concurrent use of an agent for chemical castration with a serum testosterone level < 50 ng/dL. Subjects with hormone naïve metastatic prostate cancer, must have high-volume disease, defined as extra-nodal visceral disease or bone metastases with at least 4 bone lesions (one being outside of the vertebral column or pelvis). Subjects with hormone naïve high-volume metastatic prostate adenocarcinoma must have been on androgen deprivation therapy (including luteinizing hormone-releasing hormone (LHRH) agonist therapy, LHRH antagonist therapy, or surgical castration) for less than 120 days prior to starting docetaxel therapy. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. For subjects with castrate resistant prostate cancer (CRPC), at least four weeks elapsed between withdrawal of anti-androgens (Bicalutamide, Flutamide or Nilutamide) and initiation of docetaxel therapy. For subjects with CRPC, at least four weeks elapsed between last administration of Abiraterone (Zytiga®) or Enzalutamide (Xtandi®) and initiation of docetaxel therapy. At least four weeks elapsed between prior surgery or prior radiotherapy and initiation of docetaxel therapy. Radiograph-documented evidence of soft tissue or bony metastatic disease. Must have adequate hematologic, hepatic and renal function as defined below: Hematologic (minimal values): Absolute neutrophil count ≥ 1,500/mm3; Hemoglobin ≥ 10.0 g/dl; Platelet count ≥ 75,000/mm3 Hepatic Function: Total Bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); asparate transaminase (AST) and alanine transaminase (ALT) < 2 x institutional ULN Suitable venous access and healthy enough (as determined by the treating physician) to provide whole blood sample. Exclusion Criteria: Any condition / concomitant disease not allowing chemotherapy with docetaxel, prednisone or required premedication for the treatment regimen. Serious concurrent disorders (active infection requiring intravenous antibiotics, unstable angina, uncompensated congestive heart failure (CHF), or hepatic failure) that, in the opinion of the investigator, would prevent the use of docetaxel and/or compromise the subject's ability to provide whole blood samples for participation in the study. Concurrent use of any non-FDA approved (i.e. investigational or experimental) anticancer agent(s) or within four (4) weeks of enrolling on the study. Pre-existing neuropathy ≥ grade 2 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4. Individuals with known seropositivity for human immunodeficiency virus (HIV), hepatitis C virus, hepatitis B surface antigen, or syphilis. Unwilling or unable to follow protocol requirements or to provide informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| hormone naïve<br>Subjects with hormone naïve metastatic prostate cancer that have high-volume disease and have been on androgen deprivation therapy for less than 120 days prior to starting docetaxel therapy. | Drug: docetaxel<br>* 3-weekly docetaxel therapy (starting dose of 75 mg/m2)<br>* Other names: Taxotere;Other: Blood draws<br>* Blood draws for determination of docetaxel plasma levels and exposure (AUC)<br>|
| castrate resistant<br>Subjects with castrate resistant prostate cancer (CRPC) [defined as having evidence of prostate specific antigen (PSA) progression despite androgen deprivation therapy] that have had at least four weeks elapse between the withdrawal of anti-androgens (Bicalutamide, Flutamide or Nilutamide) and the initiation of docetaxel therapy. | Drug: docetaxel<br>* 3-weekly docetaxel therapy (starting dose of 75 mg/m2)<br>* Other names: Taxotere;Other: Blood draws<br>* Blood draws for determination of docetaxel plasma levels and exposure (AUC)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variability of docetaxel exposure | Blood will be drawn during the first six cycles of docetaxel therapy to determine the variability of docetaxel exposure. | Up to 6 months after the initiation of docetaxel therapy | 
| Docetaxel treatment related toxicities | Determine the relationship between docetaxel plasma concentrations (i.e. exposure level) and the incidence of docetaxel related toxicities for identification of an optimal target docetaxel exposure range. | Up to 7 months after the initiation of docetaxel therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of growth factor usage | Determine relationship (if any) between growth factor usage and docetaxel exposure levels. | Up to 7 months after the initiation of docetaxel therapy | 
| Number of days hospitalized for treatment of docetaxel related toxicities | Determine relationship (if any) between number of day hospitalized due to treatment related toxicities and docetaxel exposure levels. | Up to 7 months after the initiation of docetaxel therapy | 
| Time to prostate specific antigen (PSA) progression | Determine relationship (if any) between the time to PSA progression and docetaxel exposure levels obtained during the first 6 cycles of treatment. | Up to 24 months after the initiation of docetaxel therapy | 
| Tumor response as determined by imaging | Determine relationship (if any) between the tumor response as determined by imaging and docetaxel exposure levels obtained during the first 6 cycles of treatment. | Up to 7 months after the initiation of docetaxel therapy | 
| Changes in quality of life | Determine relationship between changes in the quality of life (as measured using the FACT-P Questionnaire) and docetaxel exposure levels obtained during the first 6 cycles of treatment. | Up to 6 months after the initiation of docetaxel therapy | 
| Overall survival | Determine relationship between overall survival and docetaxel exposure levels obtained during the first 6 cycles of treatment. | Up to 24 months after the initiation of docatexel therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRPC, metastatic prostate cancer, castrate resistant prostate cancer, hormone sensitive prostate cancer