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

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ClinicalTrials.gov Identifier: NCT02430480
Recruitment Status : Active, not recruiting
First Posted : April 30, 2015
Last Update Posted : June 3, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information
First Submitted Date  ICMJE April 28, 2015
First Posted Date  ICMJE April 30, 2015
Last Update Posted Date June 3, 2019
Actual Study Start Date  ICMJE June 3, 2015
Estimated Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2018)
Feasiblity of mpMRI before and after surgery [ Time Frame: 6 months ]
localization and detections of focal prostate cancer before and aftertreatment with mpMRI
Original Primary Outcome Measures  ICMJE
 (submitted: April 28, 2015)
Feasiblity of mpMRI before and after surgery [ Time Frame: 6 months ]
Change History Complete list of historical versions of study NCT02430480 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Using Multiparametric MRI to Evaluate Intraprostatic Tumor Responses and Androgen Resistance Patterns in Newly Diagnosed Prostate Cancer
Official Title  ICMJE Neoadjuvant Androgen Deprivation and Enzalutamide: Using Multiparametric MRI to Evaluate Intraprostatic Tumor Responses and Androgen Resistance Patterns in Newly Diagnosed Prostate Cancer
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.
  • ECG heart test, with patches stuck on the skin.
  • Small piece of tumor removed (biopsy) using image guidance from MRI and ultrasound.
  • 3T mpMRI. Participants will lie on a table that slides into a metal cylinder. A probe will be inserted in the <TAB>rectum. They will be in the scanner for about 60 minutes, lying still. The scanner makes loud knocking <TAB>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.
  • 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 (MR/US guided) samples
  • Standard of care prostatectomy(RP) following post treatment mpMRI
  • All tumor specimens will undergo genomic analysis
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: Goserelin
    10.8mg administered subcutaneously every 12 weeks (2 doses)
  • Procedure: mpMRI
    Multiparametric MRI - One at baseline and after 6 months of treatment
Study Arms  ICMJE Experimental: 1/Arm 1
Patients will have an mpMRI guided biopsy, then receive enzalutamide and goserelin SC treatment for 6 months followed by a second mpMRI examination.
Interventions:
  • Drug: Goserelin
  • Procedure: mpMRI
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 31, 2019)
38
Original Estimated Enrollment  ICMJE
 (submitted: April 28, 2015)
55
Estimated Study Completion Date  ICMJE June 1, 2020
Estimated Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:
  • Patients must have histologically or cytologically confirmed prostate cancer confirmed by the Laboratory of Pathology, 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:

      • 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 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.
  • 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
  • AST(SGOT)/ALT(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 m2 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 MRI for biopsy
  • Willingness to travel to 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 (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
    • PT/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 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 CYP3A4 or 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 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02430480
Other Study ID Numbers  ICMJE 150124
15-C-0124
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: William L Dahut, M.D. National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date May 30, 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP