Phase 2 N=39 Diagnostic

Using Multiparametric MRI to Evaluate Intraprostatic Tumor Responses and Androgen Resistance Patterns in Newly Diagnosed Prostate Cancer

Prostate Cancer

Bottom Line

View on ClinicalTrials.gov: NCT02430480 ↗

Enrolled (actual)

Serious AEs

5.1%

Results posted

Nov 2020

Primary outcome: Primary: Median Tumor Volume Burden at Baseline Multi-parametric Magnetic Resonance Imaging (mpMRI) Before and After Surgery — 3.44; 0.62 cc

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Goserelin (Drug); Enzalutamide (Drug); mpMRI (Device)
Age: Adult, Older Adult · 18+ yrs
Sex: Male
Sponsor: National Cancer Institute (NCI)
Primary completion: Dec 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Median Tumor Volume Burden at Baseline Multi-parametric Magnetic Resonance Imaging (mpMRI) Before and After Surgery	3.44; 0.62	—
SECONDARY Median Nuclear Androgen Receptor (AR) Level in Biopsy Specimens Versus Residual Tumors	0.7568; 0.1661	—
SECONDARY Median Prostate Lesion Volume Before and After Treatment	39.5; 20.0	—
SECONDARY Number of Participants With a Complete Response	2	—
SECONDARY Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	38	—
SECONDARY Number of Prostate Lesions Detected Within the Study Population at Baseline Multi-parametric Magnetic Resonance Imaging (mpMRI) and 6 Months After Enzalutamide Plus Androgen Deprivation Therapy (ADT)	58; 40	—
SECONDARY Initial Multiparametric Magnetic Resonance Imaging (mpMRI) Percentage of Relative Tumor Volume Sensitivity	81	—
SECONDARY Number of Participants With Reduction in Phosphatase and Tensin Homolog (PTEN) Levels	21	—
SECONDARY Number of Participants With Positive Erythroblast Transformation-specific (ETS)-Related Gene (ERG) Protein Overexpression	14	—
SECONDARY Initial Multiparametric Magnetic Resonance Imaging (mpMRI) Percentage of Relative Tumor Volume Specificity	87	—

Summary

Background: * There are several ways to treat prostate cancer. Researchers want to see how well a certain kind of imaging helps detect prostate cancer. They also want to see if a particular drug combination used before surgery will benefit people with prostate cancer that hasn't spread in the body (non-metastatic). The combination will be androgen deprivation therapy and enzalutamide. * The combination of androgen deprivation therapy and enzalutamide has been shown to make patients with advanced (metastatic disease) live longer. The investigators want to see if using it earlier can increase cure rate of surgery and identify genetic or molecular characteristics that are associated with better outcomes. Objectives: - To develop better ways of detecting prostate cancer before and after pre-operative treatment. Eligibility: - Men at least 18 years old with non-metastatic prostate cancer. They must be candidates for a radical prostatectomy. Design: * Participants will be screened with medical history, physical exam, and blood tests. They will have scans and X-rays. * Before starting the study drugs, participants will have: * Vital signs taken, medical history, and blood tests. * Electrocardiogram (ECG) heart test, with patches stuck on the skin. * Small piece of tumor removed (biopsy) using image guidance from magnetic resonance imaging (MRI) and ultrasound. * 3T multi-parametric magnetic resonance imaging (mpMRI). Participants will lie on a table that slides into a metal cylinder. A probe will be inserted in the rectum. They will be in the scanner for about 60 minutes, lying still. The scanner makes loud knocking sounds. Participants will get earplugs. * Participants will take the 2 study drugs for 6 months. * Enzalutamide is taken as 4 pills once a day. * Androgen deprivation therapy is given by injection 2 times over 6 months. * During these 6 months, participants will visit the clinic monthly. They will have physical exam, vital signs, and blood drawn. * After finishing the study drugs, participants will have another 3T mpMRI. Then they will have prostate removal surgery.

Eligibility Criteria

INCLUSION CRITERIA:
Patients must have histologically or cytologically confirmed prostate cancer confirmed by the Laboratory of Pathology, National Cancer Institute (NCI) or Pathology Department at Walter Reed Bethesda
Must have previously untreated (with definitive therapy) prostate cancer with intermediate or high risk features defined as:
Intermediate risk:
Prostate-specific antigen, (PSA) level is between 10 and 20 ng/ml or
Gleason score is 7 or
Stage T2b or T2c
High Risk:
Gleason 8 and higher OR
PSA greater than 20 at the time of diagnosis OR
Seminal vesicle involvement OR
Possible (on magnetic resonance imaging (MRI) Extra-capsular extension (T3 disease)
Patients must be eligible for and must be planning to undergo radical prostatectomy
Patients must have testosterone levels greater than or equal to 100 ng/dL
Men age greater than or equal to 18 years.
Children are excluded because prostate cancer is not common in pediatric populations.
Women are not eligible because this disease occurs only in men.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
Patients must have normal organ and marrow function as defined below:
Hemoglobin greater than or equal to 9 g/dL
leukocytes greater than or equal to 3,000/mcL
absolute neutrophil count greater than or equal to 1,500/mcL
platelets greater than or equal to 150,000/mcL
total bilirubin within normal institutional limits
Aspartate aminotransferase (AST)/Serum glutamic-oxaloacetic transaminase(SGOT)/Alanine aminotransferase (ALT) Serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 X institutional upper limit of normal
creatinine within normal institutional limits

creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.
The effects of enzalutamide on the developing human fetus are unknown. For this reason and because androgen receptor antagonists as well as other therapeutic agents used in this trial are known to be teratogenic, male participants and their female partners of child bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence). Male participants should use a condom if having intercourse with a pregnant woman. Additionally, a condom plus another effective method of birth control is recommended during therapy and for 3 months after treatment for male participants having intercourse with a woman of reproductive potential. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.
Ability of subject to understand and the willingness to sign a written informed consent document.
Willingness to undergo biopsy.
Ability to detect lesions within prostate on magnetic resonance imaging (MRI) for biopsy
Willingness to travel to National Institutes of Health (NIH) for follow-up visits.

EXCLUSION CRITERIA

Patients who are receiving any other investigational agents (in the past 28 days) or herbal medications (within 1 day).
Patients with distant metastatic disease beyond N1(regional) lymph nodes on conventional imaging studies (Computed tomography (CT), MRI or Bone Scan).
Patients who have received any prior therapy for prostate cancer with surgery, radiation, and/or chemotherapy
History of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide or other agents used in study.
Clinically significant cardiac disease, e.g. New York Heart Association (NYHA) classes III-IV; uncontrolled angina, uncontrolled arrhythmia or uncontrolled hypertension, myocardial infarction in the previous 6 months as confirmed by an electrocardiogram (ECG).
Contraindication to biopsy:
Bleeding disorders
Prothrombin Time (PT)/Partial Thromboplastin Time (PTT) greater than or equal to 1.5 times the up

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02430480). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.