Prospective Biomarker Analysis of Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) Undergoing Sequential Treatment With Docetaxel and Enzalutamide
Overview
- Phase
- Phase 2
- Intervention
- Docetaxel
- Conditions
- Prostate Cancer
- Sponsor
- Instituto do Cancer do Estado de São Paulo
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Correlate AR-V7 status in circulating tumor cells (positive versus negative) and PSA response decline > 50% after therapy with docetaxel
- Status
- Active, Not Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a prospective biomarker study of patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing sequential treatment with docetaxel and enzalutamide. The participants will undergo serial pre- and post-therapy blood collection for biomarker analysis as part of the primary objective of the study. The primary goal of this study is to evaluate the association of the AR-V7 status and androgen receptor (AR) gene alterations with PSA response to docetaxel and enzalutamide.
Detailed Description
This study is a prospective biomarker study of patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing sequential treatment with docetaxel followed by enzalutamide. In this study, all participants will receive standard of care treatment with docetaxel 75 mg/m2 every 3 weeks up to 10 cycles and after progression, patients will receive enzalutamide 160 mg daily until limiting toxicity or disease progression. The participants will undergo serial pre- and post-therapy blood collection for biomarker analysis as part of the primary objective of the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years
- •Men diagnosed with metastatic prostate cancer, with at least one metastatic lesion on CT or bone scan.
- •Documentation of castrate levels of testosterone (\< 50 ng per deciliter), and continued androgen deprivation therapy or surgical castration.
- •Progressive disease at study entry defined as one or more of the following three criteria that occurred while the patient was on androgen deprivation therapy:
- •PSA progression defined by a minimum of two rising PSA levels with an interval of ≥
- •1 week between each determination. Patients who received an anti-androgen must have progression after withdrawal (≥ 4 weeks since last flutamide, bicalutamide or nilutamide). The PSA value at the Screening visit should be ≥ 2 μg/L (2 ng/mL);
- •Soft tissue disease progression defined by RECIST 1.1;
- •Bone disease progression defined by PCWG2 with two or more new lesions on bone scan.
- •No prior chemotherapy for mCRPC.
- •Patients previously treated with bicalutamide, ketoconazole, or estrogens will be eligible. These patients must have discontinued therapy ≥ 4 weeks prior to enrollment.
Exclusion Criteria
- •Patients with CRPC previously treated with chemotherapy.
- •Non-castrate levels of testosterone (\> 50 ng per deciliter) or inability to continue androgen deprivation therapy during the study period.
- •Absence of detectable metastasis on imaging studies.
- •Prior therapy with abiraterone, enzalutamide or any investigational AR-directed agent.
- •Contra-indication for therapy with docetaxel or enzalutamide.
- •History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma). History of loss of consciousness or transient ischemic attack within 12 months of enrollment.
- •Known or suspected brain metastasis or active leptomeningeal disease.
- •Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment;
- •History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer;
- •Absolute neutrophil count \< 1,500/μL, or platelet count \< 100,000/μL, or hemoglobin \< 9 g/dL at the Screening visit;
Arms & Interventions
Study cohort
Docetaxel 75 mg/m2 i.v. every 3 weeks for 6-10 cycles. Upon disease progression after docetaxel, participants will receive enzalutamide 160 mg p.o. daily until limiting toxicity or disease progression.
Intervention: Docetaxel
Study cohort
Docetaxel 75 mg/m2 i.v. every 3 weeks for 6-10 cycles. Upon disease progression after docetaxel, participants will receive enzalutamide 160 mg p.o. daily until limiting toxicity or disease progression.
Intervention: Enzalutamide
Outcomes
Primary Outcomes
Correlate AR-V7 status in circulating tumor cells (positive versus negative) and PSA response decline > 50% after therapy with docetaxel
Time Frame: 6 months
Correlate AR-V7 status in circulating tumor cells (positive versus negative) and PSA decline > 50% after therapy with enzalutamide
Time Frame: 12 months
Correlate AR mutations (present versus absent) and PSA response decline > 50% after therapy with docetaxel.
Time Frame: 6 months
Correlate AR mutations (present versus absent) and PSA response decline > 50% after therapy with enzalutamide.
Time Frame: 12 months
Secondary Outcomes
- Correlate AR mutations (present versus absent) and time to PSA progression after docetaxel.(12 months)
- Correlate AR-V7 status in circulating tumor cells (positive versus negative) and overall survival.(24 months)
- Correlate AR mutations (present versus absent) and median overall survival.(24 months)
- Correlate AR-V7 status in circulating tumor cells (positive versus negative) and time to PSA progression after docetaxel.(12 months)
- Correlate AR-V7 status in circulating tumor cells (positive versus negative) and time to PSA progression after enzalutamide.(12 months)
- Correlate AR mutations (present versus absent) and time to PSA progression after enzalutamide.(12 months)