Molecular Features and Pathways in Predicting Drug Resistance in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Enzalutamide

NCT ID: NCT02228265

Last Updated: 2020-09-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 41 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-03-12
• Study Completion Date: 2020-02-27

Brief Summary

This research trial studies molecular features and pathways in predicting drug resistance in patients with castration-resistant prostate cancer that has spread to other parts of the body and who are receiving enzalutamide. Studying samples of blood and tissue in the laboratory from patients receiving enzalutamide may help doctors learn more about molecular features and pathways that may cause prostate cancer to be resistant to the drug.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the correlations between baseline molecular features and pathways and prostate-specific antigen (PSA) response (</>= 50% decline) at 12 weeks versus (vs.) baseline.

SECONDARY OBJECTIVES:

I. To assess the correlations between the baseline molecular features and pathways and progression-free survival (defined as time from day 1 of study drug treatment to date of radiographic progression or clinical progression), disease-specific survival (defined as the time from day 1 of study drug to date of death from prostate cancer), and overall survival (defined as time from day 1 of study drug treatment to date of death from any cause).

II. To assess the correlations between the baseline molecular features and pathways and time to PSA progression.

III. To identify molecular features and cellular pathways present in tumors from men with metastatic castrate-resistant prostate cancer (CRPC) that are progressing despite enzalutamide treatment.

IV. To explore correlation between baseline molecular features and pathways and objective response.

V. To assess the correlations between the baseline molecular features and pathways and degree of PSA decline at 12 weeks and maximal PSA decline observed while on study.

VI. To assess the correlations between the baseline molecular features and time on treatment.

TERTIARY OBJECTIVES:

I. To assess correlations between cell-free deoxyribonucleic acid (cfDNA) molecular features from blood and molecular features and pathways from the biopsy samples.

II. To assess correlations between cfDNA molecular features and endpoints in the primary and secondary objectives listed above.

III. To explore correlations with baseline molecular features and tissue histology.

IV. To explore correlations with baseline tissue histology and PSA change, time to PSA progression, time on treatment, progression-free survival, and overall survival.

OUTLINE:

Patients undergo collection of blood and tissue samples at baseline, during administration of enzalutamide, and after the time of disease progression for analysis via immunohistochemistry, comparative genome hybridization, and sequencing.

After completion of study, patients are followed up every 12 weeks.

Conditions

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Prostate Adenocarcinoma; PSA Progression; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Ancillary-Correlative (genetic analysis)

Patients undergo collection of blood and tissue samples at baseline, during administration of enzalutamide and after the time of disease progression for analysis via immunohistochemistry, comparative genome hybridization, and sequencing.

Cytology Specimen Collection Procedure

Intervention Type: OTHER

Undergo blood and tissue collection

Enzalutamide

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Cytology Specimen Collection Procedure

Undergo blood and tissue collection

Intervention Type: OTHER

Enzalutamide

Given PO

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Cytologic Sampling; ASP9785; MDV3100; Xtandi

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
• Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration); for patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial
• Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy
• Willingness to undergo a tumor biopsy at baseline and at disease progression
• Serum testosterone level < 50 ng/dL at screening
• Progressive disease by PSA or imaging in the setting of medical or surgical castration; disease progression for study entry is defined as one or more of the following three criteria:

• PSA progression defined by a minimum of three rising PSA levels with an interval of >= 1 week between each determination; the PSA value at screening should be >= 2 ug/L (2 ng/ml)
• Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
• Bone disease progression defined by two or more new lesions on bone scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Clinically able, in the opinion of the investigator, to receive MDV3100 (enzalutamide)
• Willing and able to give informed consent
• A minimum of 4 weeks elapsed off of anti-androgen therapy prior to enrollment for flutamide and 6 weeks for bicalutamide and nilutamide without evidence of an anti-androgen withdrawal response; patients who NEVER HAD A PSA decline with the most recent anti-androgen therapy or in whom the response to the most recent anti-androgen was for < 3 months require only a 2 week washout period prior to first dose of study drug

Exclusion Criteria

• Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment
• Metastases in the brain or active epidural disease (NOTE: patients with treated epidural disease are allowed)
• Platelet count < 75,000/uL
• Prothrombin time (PT) or international normalized ratio (INR) and a partial thromboplastin time PTT > 1.5 times the institutional upper limit of normal (ULN)
• Structurally unstable bone lesions suggesting impending fracture
• Previous treatment with MDV3100, ARN-509, or BMS-641988
• Medical contraindications to stopping aspirin, Coumadin or other anticoagulants for 1 week prior to image-guided tumor biopsies
• Plans to initiate treatment with an investigational agent while on study prior to discontinuation of MDV3100 treatment
• A second active malignancy except adequately treated non-melanoma skin cancer or other non-invasive or in situ neoplasm

• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Oregon Health and Science University

OTHER

Sponsor Role: collaborator

OHSU Knight Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Tom Beer

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joshi Alumkal

Role: PRINCIPAL_INVESTIGATOR

OHSU Knight Cancer Institute

Locations

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

UCSF Medical Center-Mount Zion

San Francisco, California, United States

OHSU Knight Cancer Institute

Portland, Oregon, United States

Countries

United States

Other Identifiers

NCI-2014-01438

Identifier Type: REGISTRY

Identifier Source: secondary_id

MR00046920

Identifier Type: -

Identifier Source: secondary_id

IRB00009259

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00009259

Identifier Type: -

Identifier Source: org_study_id