Biomarker Analysis of Castration-resistant Prostate Cancer Undergoing Treatment With Docetaxel Followed by Enzalutamide

NCT03700099 | Active Not Recruiting Phase 2

• 1 other identifier: NP 1082/17
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer; Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (4)

• Correlate AR-V7 status in circulating tumor cells (positive versus negative) and PSA response decline > 50% after therapy with docetaxel

  6 months

• Correlate AR-V7 status in circulating tumor cells (positive versus negative) and PSA decline > 50% after therapy with enzalutamide

  12 months

• Correlate AR mutations (present versus absent) and PSA response decline > 50% after therapy with docetaxel.

  6 months

• Correlate AR mutations (present versus absent) and PSA response decline > 50% after therapy with enzalutamide.

  12 months

Secondary Outcomes (6)

• 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 docetaxel.

  12 months

• Correlate AR mutations (present versus absent) and time to PSA progression after enzalutamide.

  12 months

• Correlate AR-V7 status in circulating tumor cells (positive versus negative) and overall survival.

  24 months

Study Arms (1)

Study cohort

OTHER

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.

Drug: Docetaxel; Drug: Enzalutamide

Interventions

Docetaxel DRUG

Docetaxel 75 mg/m2 IV every 3 weeks, for 6-10 cycles.

Also known as: Chemotherapy

Study cohort

Enzalutamide DRUG

Upon disease progression after treatment with docetaxel, patients will receive Enzalutamide 160 mg P.O. daily until disease progression or limiting toxicity.

Also known as: Xtandi

Study cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ≥
• 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.
• Patients previously treated with steroids or receiving prednisone or dexamethasone will be eligible. In this case, continuing therapy will be at the discretion of the attending physician.
• Patients who are candidates for therapy with docetaxel and enzalutamide.
• Patients must agree to undergo pre- and post-therapy blood collection.
• Patients must understand and be willing to sign the written informed consent form of this study.

You may not qualify if:

• 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;
• Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal at the screening visit (for Docetaxel phase only);
• Creatinine \> 2 mg/dL at the Screening visit (for Docetaxel phase only);
• Albumin \< 3.0 g/dL at the Screening visit (for Docetaxel phase only);
• Clinically significant cardiovascular disease including:
• Myocardial infarction within 6 months;

Sponsors & Collaborators

• Instituto do Cancer do Estado de São Paulo: lead
• Astellas Pharma Inc: collaborator

Study Sites (1)

Instituto do Câncer do Estado de São Paulo

São Paulo, São Paulo, Brazil

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel; Drug Therapy; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Therapeutics

Study Officials

• Diogo Bastos

  Instituto do Cancer do Estado de São Paulo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2018
• First Posted: October 9, 2018
• Study Start: September 3, 2019
• Primary Completion: March 1, 2024
• Study Completion: April 1, 2025
• Last Updated: April 15, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)