A Phase II Study of Neoadjuvant Androgen Deprivation Therapy Combined With Enzalutamide and Abiraterone Using Multiparametric MRI and 18F-DCFPyL-PET/CT in Newly Diagnosed Prostate Cancer


Condition: Castrate Sensitive Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03860987

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • 1. Patients must have histologically or cytologically confirmed prostate cancer confirmed by the Laboratory of Pathology, NCI, OR documented histopathological confirmation of prostate cancer from a CLIA-certified laboratory. 2. Must have previously untreated (with definitive therapy ie: surgery, systemic treatment or radiation therapy) prostate cancer with intermediate or high risk features defined as:
  • Intermediate risk (patient must have at least one of the features listed below):
  • PSA level is between 10 and 20 ng/ml,
  • Gleason score is 7, OR
  • Stage T2b or T2c,
  • High risk (patient must have at least one of the features listed below):
  • PSA > 20 at the time of diagnosis,
  • Gleason 8 or higher,
  • Seminal vesicle involvement,
  • Possible (on MRI) extra-capsular extension (T3 disease), OR
  • Clinical stage T4 3. Patients must be eligible for and must be planning to undergo radical prostatectomy 4. Patients must have testosterone levels greater than or equal to 100 ng/dL 5. Men age greater than or equal to18 years. Children are excluded because prostate cancer is not common in pediatric populations. Women are not eligible because this disease occurs only in men. 6. ECOG performance status 0-1. 7. Patients must have adequate organ and marrow function, and other laboratory parameters as defined below:
  • hemoglobin greater than or equal to 9 g/dL
  • 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 30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (calculated via EGFR) 8. Lesions within prostate must be detectable on MRI for biopsy. 9. The effects of enzalutamide and abiraterone 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 and her partner should inform the study team. 10. Ability of subject to understand and the willingness to sign a written informed consent document. 11. Willingness to adhere to protocol requirements (e.g., required biopsies). 12. Willingness to travel to NIH for follow-up visits.

Exclusion Criteria:

  • 1. Patients who are receiving any other investigational agents (in the past 28 days) or herbal medications (within 1 day prior to registration). 2. Patients with evidence of distant metastatic disease beyond N1 (regional) lymph nodes on conventional imaging studies (e.g., CT, MRI or Bone Scan). 3. Patients who have received any prior definitive therapy (ie: surgery, systemic treatment or radiation therapy) for prostate cancer. 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide, abiraterone or other agents used in study. 5. Clinically significant cardiac disease, e.g., New York Heart Association (NYHA) classes III-IV; uncontrolled angina, uncontrolled arrhythmia or uncontrolled hypertension (greater than or equal to 160/100 mmHg on two consecutive readings), myocardial infarction in the previous 6 months as confirmed by an electrocardiogram (ECG). 6. Contraindication to biopsy:
  • Bleeding disorders for which a prostate biopsy would pose a bleeding risk
  • PT/PTT greater than or equal to 1.5 times the upper limit of normal
  • Artificial heart valve 7. Contraindication to MRI:
  • Patients weighing more than the weight limit or unable to fit the scanner
  • Allergy to MR contrast agent
  • Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic device 8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. 9. HIV-positive patients on antiretroviral therapy are ineligible because of potential pharmacokinetic interactions with study drugs. However, patients with long-standing (>5 years) HIV on antiretroviral therapy > 1 month (undetectable HIV viral load and CD4 count > 150 cells/microliter) may be eligible if the PI determines no anticipated clinically significant drug-drug interactions. 10. Patients undergoing active treatment for Hepatitis B or C infections. 11. Patients who have taken medications that are strong inhibitors or inducers of CYP3A4 or PgP within 14 days prior to enrollment and need to remain on these medications. 12. Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g., phytoestrogens and saw palmetto) cannot be taken while patients are receiving enzalutamide and abiraterone. 13. Contraindication to steroid use. 14. Patients with malignancy within the past 3 years for which study drugs or a prostatectomy is a contraindication.

View trial on ClinicalTrials.gov