Prostate CancerPhase 2NCT02430480
Using Multiparametric MRI to Evaluate Intraprostatic Tumor Responses and Androgen Resistance Patterns in Newly Diagnosed Prostate Cancer
A Phase 2 study testing Goserelin, Enzalutamide and mpMRI in people with Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Goserelin, Enzalutamide and mpMRI
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jun 2015to 11 Jun 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 32Show fewer
- 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
- OR
- 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.
Who cannot join
- 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:
Show all 21Show fewer
- 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.
- Patients with known active treatment for Hepatitis B and C infections.
- Patients who are taking medications that are strong inhibitors of Cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (PgP) and need to remain on these medications. For a current table of Substrates, Inhibitors and Inducers please access the following website:
- http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm
- History of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack, or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization).
- Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter prostate specific antigen (PSA) (eg phytoestrogens and saw palmetto) cannot be taken while patients are receiving enzalutamide
- Patients with a malignancy within the past 3 years for which study drugs or a prostatectomy is a contraindication.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Neoadjuvant Androgen Deprivation and Enzalutamide: Using Multiparametric MRI to Evaluate Intraprostatic Tumor Responses and Androgen Resistance Patterns in Newly Diagnosed Prostate Cancer
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.
Read more
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.
Read the detailed description
Background:
- Most men diagnosed with prostate cancer will present with intermediate or high-risk disease
- Many develop castrate resistant prostate cancer (CRPC) as curative strategies are often unsuccessful
- Treatment options typically involve radical prostatectomy (RP) or radiation therapy (RT) in combination with androgen deprivation therapy (ADT)
- Even when cancers are initially sensitive to ADT, resistance ultimately emerges either through clonal selection or through a variety of adaptive mechanisms (secondary resistance).
- The recent introduction of novel androgen pathway inhibitors offers an opportunity to potentially improve the cure rate of men with intermediate and high risk localized prostate cancer
- There remains a great need for improved techniques to determine mechanisms of treatment response and resistance.
Objectives:
-To test the feasibility of multi parametric magnetic resonance imaging (mpMRI) for the localization and detection of focal prostate cancer both before and after pre-operative treatment with ADT and enzalutamide.
Eligibility:
- Patients with nonmetastatic castration sensitive prostate cancer with intermediate or high-risk features
- Patients with testosterone levels greater than or equal to 100 ng/dL.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
Design:
- Patients will be treated with ADT and enzalutamide for 6 months
- Two 3T mpMRI endorectal examinations (One at screening and after 6 month of treatment)
- Screening biopsy (magnetic resonance (MR)/ultrasound (US) guided) samples
- Standard of care prostatectomy (RP) following post treatment mpMRI
- All tumor specimens will undergo genomic analysis
- Conditions
- Prostate Cancer
- Being tested
- Goserelin, Enzalutamide, mpMRI
- Keywords
- Multiparametric MRI, Prostatectomy, Focal Prostate Cancer, Normal Testosterone, Non-Metastatic
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GoserelinDrug
Also called Zoladex
10.8mg administered subcutaneously every 12 weeks (2 doses)
EnzalutamideDrug
Also called ASP-9785
160mg orally, daily for 24 weeks
mpMRIDevice
Also called multi-parametric magnetic resonance imaging
Multiparametric MRI - One at baseline and after 6 months of treatment
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Goserelin; Drug: Enzalutamide; Device: mpMRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 6 months
Secondary outcomes (9)
Median Nuclear Androgen Receptor (AR) Level in Biopsy Specimens Versus Residual Tumors
The effect of intense androgen suppression and inhibition was measured on tumors using anti-AR immunostains of biopsy and surgical specimens. Detection of tumor nuclear AR was quantified on a per-nucleus basis using computer-aided image analysis with Definiens Developer XD 64, grouping nuclei into high, medium, low, and absent bins, a histology score was assigned to each sample.
Nucleus classification is low vs. med. at 0.7; med. vs. high at 0.95. Definiens reported the total # of positively stained nuclei or cells, along with the distribution of low-, med.-, and high-intensity stained nuclei/cells for ea. tumor focus. A %positive index score was calculated using a weighted avg. divided by the total # of objects, where index = [ (1 × nuclei/cells stained low) + (2 × nuclei/cells stained med.) + (3 × nuclei/cells stained high) ](3 × total nuclei).
Measured: 6 months
Median Prostate Lesion Volume Before and After Treatment
Prostate lesion volumes on baseline and post-treatment multiparametric magnetic resonance imaging (mpMRI) were calculated from T2W-MRI sequences using software embedded in the PACS after manual contouring by the same radiologist. Lesion volume scores were categorized as low (2 or fewer positive sequences), moderate (3 positive sequences) and high (4 positive sequences). Lesion volume values are in cubic centimeters (cc's).
Measured: Baseline and 6 months
Number of Participants With a Complete Response
Complete response was evaluated after neoadjuvant treatment with androgen deprivation therapy (ADT) and enzalutamide and assessed by pathologic exam. Pathologic complete response: the absence of residual invasive cancer confirmed by immunohistochemistry (IHC).
Measured: 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)
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Measured: 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)
Prostate lesion volumes on baseline and post-treatment mpMRI were calculated from T2W-MRI sequences using software embedded in the PACS after manual contouring by the same radiologist.
Measured: Baseline and 6 months
Initial Multiparametric Magnetic Resonance Imaging (mpMRI) Percentage of Relative Tumor Volume Sensitivity
The Youden index was used as a measure for evaluating biomarker effectiveness and was calculated to determine the cutoffs that gave the optimal combination of sensitivity and specificity for patient response to treatment. The index is: J=sensitivity + specificity -1. Its value ranges from 0 through 1 (inclusive). A value of 1 indicates that there are no false positives or false negatives, i.e. the test is perfect. The index gives equal weight to false positive and false negative values, so all tests with the same value of the index give the same proportion of total misclassified results. Sensitivity and specificity are the probability of truly identifying relative tumor burden on multiparametric magnetic resonance imaging (mpMRI) respectively at a statistically established cut point.
Measured: 6 months
Number of Participants With Reduction in Phosphatase and Tensin Homolog (PTEN) Levels
PTEN level reduction was evaluated using immunohistochemistry in post treatment specimens. For anti-PTEN immunohistochemistry, a case was considered PTEN-reduced (abnormal) if at least 5% of tumor cells demonstrated reduced PTEN intensity relative to PTEN in benign cells (lower than 5%, then abnormal).
Measured: post treatment, approximately 1-3 months
Number of Participants With Positive Erythroblast Transformation-specific (ETS)-Related Gene (ERG) Protein Overexpression
ERG protein overexpression was evaluated using immunohistochemistry in post treatment specimens. A positive ETS-related ERG overexpression is a bad outcome.
Measured: Approximately one month-3 months post-treatment
Initial Multiparametric Magnetic Resonance Imaging (mpMRI) Percentage of Relative Tumor Volume Specificity
The Youden index was used as a measure for evaluating biomarker effectiveness and was calculated to determine the cutoffs that gave the optimal combination of sensitivity and specificity for patient response to treatment. The index is: J=sensitivity + specificity -1. Its value ranges from 0 through 1 (inclusive). A value of 1 indicates that there are no false positives or false negatives, i.e. the test is perfect. The index gives equal weight to false positive and false negative values, so all tests with the same value of the index give the same proportion of total misclassified results. Sensitivity and specificity are the probability of truly identifying relative tumor burden on multiparametric magnetic resonance imaging (mpMRI) respectively at a statistically established cut point.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2015 (estimated)
- Study start3 Jun 2015
- Primary completion1 Dec 2019
- Study completion11 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Fatima Karzai, M.D., National Cancer Institute (NCI)
- Investigators
- Fatima Karzai, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02430480
- Sponsor's protocol ID
- 150124
- Other IDs
- 15-C-0124
- Status last verified
- Jul 2025
- First submitted
- 28 Apr 2015
- Last updated
- 16 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
Publications
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.
PubMed 40906535Rathi 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.
PubMed 39427924Karzai 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.
PubMed 33023952Gold 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.
PubMed 31000430
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Androgen Deprivation and Enzalutamide: Using Multiparametric MRI to Evaluate Intraprostatic Tumor Responses and Androgen Resistance Patterns in Newly Diagnosed Prostate Cancer
- ClinicalTrials.gov ID
- NCT02430480
- Acronym / sponsor ID
- 150124
- Conditions
- Prostate Cancer
- Keywords
- Multiparametric MRI, Prostatectomy, Focal Prostate Cancer, Normal Testosterone, Non-Metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 3 Jun 2015 (actual)
- Primary completion
- 1 Dec 2019 (actual)
- Study completion
- 11 Jun 2024 (actual)
- First posted
- 30 Apr 2015 (estimated)
- Results
- Posted 2 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background:
- Most men diagnosed with prostate cancer will present with intermediate or high-risk disease
- Many develop castrate resistant prostate cancer (CRPC) as curative strategies are often unsuccessful
- Treatment options typically involve radical prostatectomy (RP) or radiation therapy (RT) in combination with androgen deprivation therapy (ADT)
- Even when cancers are initially sensitive to ADT, resistance ultimately emerges either through clonal selection or through a variety of adaptive mechanisms (secondary resistance).
- The recent introduction of novel androgen pathway inhibitors offers an opportunity to potentially improve the cure rate of men with intermediate and high risk localized prostate cancer
- There remains a great need for improved techniques to determine mechanisms of treatment response and resistance.
Objectives:
-To test the feasibility of multi parametric magnetic resonance imaging (mpMRI) for the localization and detection of focal prostate cancer both before and after pre-operative treatment with ADT and enzalutamide.
Eligibility:
- Patients with nonmetastatic castration sensitive prostate cancer with intermediate or high-risk features
- Patients with testosterone levels greater than or equal to 100 ng/dL.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
Design:
- Patients will be treated with ADT and enzalutamide for 6 months
- Two 3T mpMRI endorectal examinations (One at screening and after 6 month of treatment)
- Screening biopsy (magnetic resonance (MR)/ultrasound (US) guided) samples
- Standard of care prostatectomy (RP) following post treatment mpMRI
- All tumor specimens will undergo genomic analysis
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1/Arm 1- Enzalutamide and Goserelin | Experimental | Drug: Goserelin, Drug: Enzalutamide, Device: mpMRIPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- 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:
- 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.
Key exclusion criteria (21 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GoserelinAlso: Zoladex10.8mg administered subcutaneously every 12 weeks (2 doses) | Drug | 1/Arm 1- Enzalutamide and Goserelin |
| EnzalutamideAlso: ASP-9785160mg orally, daily for 24 weeks | Drug | 1/Arm 1- Enzalutamide and Goserelin |
| mpMRIAlso: multi-parametric magnetic resonance imagingMultiparametric MRI - One at baseline and after 6 months of treatment | Device | 1/Arm 1- Enzalutamide and Goserelin |
Primary outcome
Median Tumor Volume Burden at Baseline Multi-parametric Magnetic Resonance Imaging (mpMRI) Before and After Surgery
Time frame: Baseline and 6 months
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.
9 secondary outcomes
Median Nuclear Androgen Receptor (AR) Level in Biopsy Specimens Versus Residual Tumors
Time frame: 6 months
Median Prostate Lesion Volume Before and After Treatment
Time frame: Baseline and 6 months
Number of Participants With a Complete Response
Time frame: 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)
Time frame: 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)
Time frame: Baseline and 6 months
Initial Multiparametric Magnetic Resonance Imaging (mpMRI) Percentage of Relative Tumor Volume Sensitivity
Time frame: 6 months
Number of Participants With Reduction in Phosphatase and Tensin Homolog (PTEN) Levels
Time frame: post treatment, approximately 1-3 months
Number of Participants With Positive Erythroblast Transformation-specific (ETS)-Related Gene (ERG) Protein Overexpression
Time frame: Approximately one month-3 months post-treatment
Initial Multiparametric Magnetic Resonance Imaging (mpMRI) Percentage of Relative Tumor Volume Specificity
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40906535Wilkinson 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.
- Derived from this study: PubMed 39427924Rathi 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.
- Derived from this study: PubMed 33023952Karzai 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.
- Derived from this study: PubMed 31000430Gold 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fatima Karzai, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Goserelin, Enzalutamide and mpMRI in people with Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Tumor Volume Burden at Baseline Multi-parametric Magnetic Resonance Imaging (mpMRI) Before and After Surgery (time frame: Baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02430480, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2025.