Clinical Trials /

Neoadjuvant Androgen Deprivation Therapy Combined With Enzalutamide and Abiraterone Using Multiparametric MRI and 18FDCFPyL PET/CT in Newly Diagnosed Prostate Cancer

NCT03860987

Description:

Background: Prostate cancer is a common cancer among men. There are several ways to treat it, including hormone blocking drugs, radiation therapy, and surgery. Researchers want to combine abiraterone and enzalutamide to see if there is a better way to treat prostate cancer. They also want to study a new radiotracer called 18F-DCFPyL, with the help of a scan called positron emission tomography/computed tomography (PET/CT) to see if there is a better way to detect prostate cancer. Objective: To develop improved techniques to localize and detect prostate cancer; and to develop new ways to treat prostate cancer Eligibility: Men ages 18 and older with prostate cancer that has not spread to other parts of the body Design: - Participants will have a medical evaluation to determine eligibility for the study. - Participants will take three different medications daily by mouth and receive two injections during the course of the study. - Participants will have a medical evaluation monthly (for 6 months) while taking the medications. - Participants will have prostate MRI and PET/CT scans before treatment, 2 months after starting treatment and again before surgery. The radiotracer will be given by injection about 2 hours before the whole-body scan. The PET/CT scan itself is about an hour. - Participants may be asked to do a biopsy before treatment and 2 months after starting treatment. - Participants will have a full medical evaluation before surgery to remove their prostate. - Participants will have a follow-up visit 3 months after surgery and then as needed. - Participants will be contacted once a year for their PSA and testosterone levels for 5 years...

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Androgen Deprivation Therapy Combined With Enzalutamide and Abiraterone Using Multiparametric MRI and 18FDCFPyL PET/CT in Newly Diagnosed Prostate Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 190062
  • SECONDARY ID: 19-C-0062
  • NCT ID: NCT03860987

Conditions

  • Castrate Sensitive Prostate Cancer

Interventions

DrugSynonymsArms
goserelin1
Enzalutamide1
Abiraterone1
18F-DCFPyL1
Prednisone1

Purpose

Background: Prostate cancer is a common cancer among men. There are several ways to treat it, including hormone blocking drugs, radiation therapy, and surgery. Researchers want to combine abiraterone and enzalutamide to see if there is a better way to treat prostate cancer. They also want to study a new radiotracer called 18F-DCFPyL, with the help of a scan called positron emission tomography/computed tomography (PET/CT) to see if there is a better way to detect prostate cancer. Objective: To develop improved techniques to localize and detect prostate cancer; and to develop new ways to treat prostate cancer Eligibility: Men ages 18 and older with prostate cancer that has not spread to other parts of the body Design: - Participants will have a medical evaluation to determine eligibility for the study. - Participants will take three different medications daily by mouth and receive two injections during the course of the study. - Participants will have a medical evaluation monthly (for 6 months) while taking the medications. - Participants will have prostate MRI and PET/CT scans before treatment, 2 months after starting treatment and again before surgery. The radiotracer will be given by injection about 2 hours before the whole-body scan. The PET/CT scan itself is about an hour. - Participants may be asked to do a biopsy before treatment and 2 months after starting treatment. - Participants will have a full medical evaluation before surgery to remove their prostate. - Participants will have a follow-up visit 3 months after surgery and then as needed. - Participants will be contacted once a year for their PSA and testosterone levels for 5 years...

Detailed Description

      Background:

        -  Most men diagnosed with prostate cancer will present with intermediate or high-risk
           disease, and 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)

        -  PET imaging based on prostate specific membrane antigen (PSMA), including use of the
           radiotracer DCFPyL, which binds PSMA, has emerged as a sensitive modality to detect
           localized and metastatic prostate cancer

        -  It is unknown how androgen-targeted therapy affects expression of the androgen-
           regulated PSMA gene, FOLH1, and 18F -DCFPyL-PET/CT sensitivity; and, the correlation
           between response on 18F -DCFPyL-PET/CT imaging and clinical response needs further
           evaluation

        -  The use of highly effective androgen pathway inhibitors enzalutamide and abiraterone
           offers an opportunity to understand the characteristics of 18F -DCFPyL-PET imaging
           during treatment while potentially improving the cure rate of men with potentially
           lethal 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 18F -DCFPyL-PET/CT for the localization of prostate cancer
      before, during, and after pre-operative treatment with ADT, enzalutamide, and
      abiraterone/prednisone in patients negative for metastatic disease

      Eligibility:

        -  Pathologic diagnosis of castration-sensitive prostate cancer with intermediate- or high-
           risk features and no evidence of metastases beyond N1 on conventional imaging

        -  Candidates for radical prostatectomy

        -  Testosterone levels greater than or equal to 100 ng/dL

        -  ECOG PS 0-1

        -  Men age greater than or equal to 18 years

      Design:

        -  Patients will be treated with ADT, enzalutamide, and abiraterone/prednisone for 6
           months, followed by standard of care radical prostatectomy (RP)

        -  18F-DCFPyL-PET/CT and mpMRI scans prior to treatment, and after 2 and 6 months of
           treatment

        -  Prostate tumor biopsy (MR/US-guided) samples for research analyses at baseline and after
           mid-treatment imaging (post-month 2)

        -  It is anticipated that approximately 1.5 to 2 years may be required for accrual of up to
           25 evaluable subjects.
    

Trial Arms

NameTypeDescriptionInterventions
1ExperimentalTreatment
  • goserelin
  • Enzalutamide
  • Abiraterone
  • 18F-DCFPyL
  • Prednisone

Eligibility Criteria

        -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 60 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. Patients with known history of HIV are ineligible. 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 and/or abiraterone. Appropriate studies
             will be undertaken in patients receiving combination antiretroviral therapy when
             indicated.

         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.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:disease status
Time Frame:2 months
Safety Issue:
Description:The primary endpoint will be the disease status after completion of treatment relative to PSMA-PET imaging findings at 2 months

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

  • Imaging
  • Prostatectomy
  • Anti-androgen Therapy
  • 18F-DCFPyL-PSMA

Last Updated

July 26, 2019