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

NCT02430480 | Completed Phase 2 Results FDA Drug FDA Device

• 2 other identifiers: 15012415-C-0124
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prostate Cancer

Keywords

Multiparametric MRI; Prostatectomy; Focal Prostate Cancer; Normal Testosterone; Non-Metastatic

Outcome Measures

Primary Outcomes (1)

• Median Tumor Volume Burden at Baseline Multi-parametric Magnetic Resonance Imaging (mpMRI) Before and After Surgery

  The prostate lesion is contoured manually by an expert radiologist. Research software (mim-vista) calculates the volume. Greater tumor volumes may indicate higher prostate tumor growth.

  Baseline and 6 months

Secondary Outcomes (9)

• Median Nuclear Androgen Receptor (AR) Level in Biopsy Specimens Versus Residual Tumors

  6 months

• Median Prostate Lesion Volume Before and After Treatment

  Baseline and 6 months

• Number of Participants With a Complete Response

  After neoadjuvant treatment with androgen deprivation therapy (ADT) and enzalutamide, approximately 6 months

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 51 months and 2 days.

• 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)

  Baseline and 6 months

Other Outcomes (1)

• Any Grade 1 Adverse Events in More Than One Patient and Grades 2 -3 Attributable to Research

  Date treatment consent signed to date off study, approximately 51 months and 2 days.

Study Arms (1)

1/Arm 1- Enzalutamide and Goserelin

EXPERIMENTAL

Patients will have an multi-parametric magnetic resonance imaging (mpMRI) guided biopsy, then receive enzalutamide and goserelin subcutaneous (SC) treatment for 6 months followed by a second mpMRI examination.

Drug: Goserelin; Drug: Enzalutamide; Device: mpMRI

Interventions

Goserelin DRUG

10.8mg administered subcutaneously every 12 weeks (2 doses)

Also known as: Zoladex

1/Arm 1- Enzalutamide and Goserelin

Enzalutamide DRUG

160mg orally, daily for 24 weeks

Also known as: ASP-9785

1/Arm 1- Enzalutamide and Goserelin

mpMRI DEVICE

Multiparametric MRI - One at baseline and after 6 months of treatment

Also known as: multi-parametric magnetic resonance imaging

1/Arm 1- Enzalutamide and Goserelin

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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 upper limit of normal
• Artificial heart valve
• Contraindication to MRI:
• Patients weighing more than weight limit for the scanner tables
• Allergy to MR contrast agent
• Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic device
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with known human immunodeficiency virus (HIV) are eligible. These patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. In addition, if patients are receiving combination antiretroviral therapy, there is potential for pharmacokinetic interactions with enzalutamide. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Wilkinson S, Ku AT, Lis RT, King IM, Low D, Trostel SY, Bright JR, Terrigino NT, Baj A, Summerbell ER, Heyward KE, Kartal S, Fenimore JM, Li C, Singler C, Vo B, Jansen CS, Ye H, Whitlock NC, Harmon SA, Carrabba NV, Atway R, Lake R, Takeda DY, Kissick HT, Pinto PA, Choyke PL, Turkbey B, Dahut WL, Karzai F, Sowalsky AG. Localized high-risk prostate cancer harbors an androgen receptor activity-low subpopulation susceptible to HER2 inhibition. J Clin Invest. 2025 Sep 4;135(22):e189900. doi: 10.1172/JCI189900. eCollection 2025 Nov 17.

  PMID: 40906535 DERIVED

• Rathi N, Blake Z, Hyman J, Nemirovsky DR, Gelikman DG, Hesswani C, Koller C, Nethala D, Mendhiratta N, Kenigsberg AP, Noun J, Dahut W, Karzai FY, Linehan WM, Pinto PA, Turkbey B, Gurram S. Castration Levels of Testosterone Results in Atrophy of Androgen-sensitive Perineal Muscles: A Potential Biomarker for Male Hypogonadism. Urology. 2025 Feb;196:313-320. doi: 10.1016/j.urology.2024.10.006. Epub 2024 Oct 18.

  PMID: 39427924 DERIVED

• Karzai F, Walker SM, Wilkinson S, Madan RA, Shih JH, Merino MJ, Harmon SA, VanderWeele DJ, Cordes LM, Carrabba NV, Bright JR, Terrigino NT, Chun G, Bilusic M, Couvillon A, Hankin A, Williams MN, Lis RT, Ye H, Choyke PL, Gulley JL, Sowalsky AG, Turkbey B, Pinto PA, Dahut WL. Sequential Prostate Magnetic Resonance Imaging in Newly Diagnosed High-risk Prostate Cancer Treated with Neoadjuvant Enzalutamide is Predictive of Therapeutic Response. Clin Cancer Res. 2021 Jan 15;27(2):429-437. doi: 10.1158/1078-0432.CCR-20-2344. Epub 2020 Oct 6.

  PMID: 33023952 DERIVED

• Gold SA, VanderWeele DJ, Harmon S, Bloom JB, Karzai F, Hale GR, Marhamati S, Rayn KN, Mehralivand S, Merino MJ, Gulley JL, Bilusic M, Madan RA, Choyke PL, Turkbey B, Dahut W, Pinto PA. mpMRI preoperative staging in men treated with antiandrogen and androgen deprivation therapy before robotic prostatectomy. Urol Oncol. 2019 Jun;37(6):352.e25-352.e30. doi: 10.1016/j.urolonc.2019.01.012. Epub 2019 Apr 15.

  PMID: 31000430 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Goserelin; enzalutamide; Multiparametric Magnetic Resonance Imaging

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)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Magnetic Resonance Imaging; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Results Point of Contact

• Title: Dr. Fatima Karzai
• Organization: National Cancer Institute

karzaifh@mail.nih.gov

301-480-7174

Study Officials

• Fatima Karzai, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 28, 2015
• First Posted: April 30, 2015
• Study Start: June 3, 2015
• Primary Completion: December 1, 2019
• Study Completion: June 11, 2024
• Last Updated: July 16, 2025
• Results First Posted: November 2, 2020

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to the Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)