Clinical Trials /

Enzalutamide With or Without Radium Ra 223 Dichloride in Patients With Metastatic, Castration-Resistant Prostate Cancer

NCT03344211

Description:

This randomized phase II trial studies how well enzalutamide with or without radium Ra 223 dichloride in treating patients with castration-resistant prostate cancer that has spread to other places in the body. Enzalutamide is an androgen receptor inhibitor that may slow down the growth of prostate cancer by blocking the action of the male hormone testosterone and other male hormones called androgens. Radiation therapy uses high energy alpha particles to kill tumor cells and shrink tumors. Enzalutamide with or without radium Ra 223 dichloride may work better in treating patients with castration-resistant prostate cancer.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Enzalutamide With or Without Radium Ra 223 Dichloride in Patients With Metastatic, Castration-Resistant Prostate Cancer
  • Official Title: Immune Activation and Cellular Response From Enzalutamide Alone or With Radium223 in Men With Metastatic, Castration-Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 4P-16-2
  • SECONDARY ID: NCI-2017-01418
  • SECONDARY ID: 4P-16-2
  • SECONDARY ID: P30CA014089
  • NCT ID: NCT03344211

Conditions

  • Castration-Resistant Prostate Carcinoma
  • Prostate Carcinoma Metastatic in the Bone
  • Stage IV Prostate Cancer

Interventions

DrugSynonymsArms
EnzalutamideASP9785, MDV3100, XtandiArm I (enzalutamide, radium 223)

Purpose

This randomized phase II trial studies how well enzalutamide with or without radium Ra 223 dichloride in treating patients with castration-resistant prostate cancer that has spread to other places in the body. Enzalutamide is an androgen receptor inhibitor that may slow down the growth of prostate cancer by blocking the action of the male hormone testosterone and other male hormones called androgens. Radiation therapy uses high energy alpha particles to kill tumor cells and shrink tumors. Enzalutamide with or without radium Ra 223 dichloride may work better in treating patients with castration-resistant prostate cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate changes in prostate cancer bone involvement induced by enzalutamide alone or
      in combination with radium Ra 223 dichloride (radium 223), specifically extent of prostate
      cancer infiltration, androgen receptor (AR) signaling and hormone levels, hematopoietic
      composition, apoptosis and proliferation.

      II. To evaluate the immune activation of enzalutamide alone, or with radium 223.

      SECONDARY OBJECTIVES:

      I. To describe the adverse event profile for the combination in this patient population.

      II. Rate of undetectable prostate specific antigen (PSA) nadir, PSA and alkaline phosphatase
      changes, rate of symptomatic skeletal events at 12 months, and rate of PSA and radiographic
      progression at 12 months.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive enzalutamide orally (PO) daily on days 1-28. Courses repeat every 28
      days in the absence of disease progression or unacceptable toxicity. Patients also receive
      radium Ra 223 dichloride intravenously (IV) on day 1. Treatment repeats every 28 days for up
      to 6 courses in the absence of disease progression or unacceptable toxicity.

      ARM II: Patients receive enzalutamide as in Arm I. Courses repeat every 28 days in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 1.5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (enzalutamide, radium 223)ExperimentalPatients receive enzalutamide PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive radium Ra 223 dichloride IV on day 1. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
  • Enzalutamide
Arm II (enzalutamide)ExperimentalPatients receive enzalutamide as in Arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Enzalutamide

Eligibility Criteria

        Inclusion Criteria:

          -  Men with metastatic, castration resistant prostate cancer involving the bone, which is
             symptomatic or asymptomatic

          -  Castration resistance will be defined as the development of disease progression,
             defined as one of the following:

               -  Rising PSA x 2 values >= 2 weeks apart; minimum absolute PSA value 2 ng/mL

               -  Radiographic progression, with at least 1 new site of metastasis

               -  Symptomatic progression (ex: increase in pain despite stable imaging) AND despite
                  ongoing luteinizing hormone-releasing hormone (LHRH) therapy OR testosterone
                  level < 50

          -  Men must have osseous metastases, but the presence of visceral metastases will not
             exclude patients from participation

               -  Prior external beam radiation therapy (> 4 weeks prior to enrollment) for
                  palliation of osseous metastatic disease is allowed, provided there is at least
                  one osseous metastasis which has not been irradiated and which can be biopsied

          -  No prior docetaxel or cabazitaxel chemotherapy for metastatic castration-resistant
             prostate cancer (mCRPC) (men treated with prior docetaxel administered as up-front
             therapy with androgen deprivation therapy [ADT] > 6 months ago will be eligible);
             prior abiraterone is allowed

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Hemoglobin >= 9.5 g/dL

          -  Absolute neutrophil count >= 1,500

          -  Platelets >= 100,000

          -  Total bilirubin within normal institutional limits

          -  Creatinine clearance (calculated or measured) > 30 mL/min

          -  At least one risk factor predicting higher likelihood of bone marrow sample yield:
             elevated alkaline phosphatase, low hemoglobin, or elevated lactate dehydrogenase (LDH)

          -  Ability to understand and the willingness to sign a written informed consent

        Exclusion Criteria:

          -  Prior treatment with docetaxel or cabazitaxel for mCRPC

          -  Prior treatment with ARN-509 or enzalutamide (there is a grace period for men who wish
             to enroll and who have recently started enzalutamide for the first time but have taken
             less than 15 days of therapy)

               -  Concurrent use of androgen deprivation therapy aside from LHRH agonist or
                  antagonist (i.e. bicalutamide, flutamide, nilutamide, abiraterone, ketoconazole,
                  estrogen); there will be a 2 week wash-out period from the last dose of any of
                  these agents until the first dose of enzalutamide on study; patients who have
                  just started enzalutamide for fewer than 5 doses prior to enrollment in the trial
                  are still considered eligible and not subject to wash-out

          -  Concurrent oral corticosteroid use aside from adrenal replacement, or use of other
             immunosuppressive agents (ex: infliximab); topical or inhaled steroids will be allowed

          -  Received systemic therapy with radionuclides (e.g., strontium-89, samarium- 153,
             rhenium-186, or rhenium-188, or radium Ra 223 dichloride) for the treatment of bony
             metastases

          -  History of seizures except for remote with specific etiology which has resolved (ex:
             alcohol induced seizure); transient ischemic attack (TIA) or cerebrovascular accident
             (CVA) within last 6 months

          -  Known untreated central nervous system (CNS) metastases; leptomeningeal disease will
             be an absolute exclusion criterion due to limited life expectancy

          -  Chronic diarrhea > grade 1, or a diagnosis of Crohn?s or ulcerative colitis

          -  Known hepatitis (hep) B or C, or known cirrhosis (screening for viral hepatitis is not
             required)

          -  Uncontrolled intercurrent illness such as infection, symptomatic congestive heart
             failure, unstable angina pectoris, or psychiatric illness which would limit compliance
             with study requirements

          -  Imminent spinal cord compression based on clinical findings and/or magnetic resonance
             imaging (MRI); treatment should be completed for spinal cord compression
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Changes in prostate cancer bone involvement
Time Frame:Up to 1.5 years
Safety Issue:
Description:Will be determined by standard pathologic analysis of the biopsies.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Southern California

Last Updated

December 10, 2018