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Randomized Salvage Radiation Therapy Plus Enzalutamide Post Prostatectomy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02203695
Recruitment Status : Active, not recruiting
First Posted : July 30, 2014
Last Update Posted : May 31, 2023
Astellas Pharma Inc
Medivation, Inc.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
The primary hypothesis of this study is that outcomes for patients with biochemically recurrent prostate cancer following radical prostatectomy will be improved by the addition of enzalutamide for 6-months compared to standard-of-care salvage radiation therapy to allow for further study in the definitive phase III setting. This study builds on the prior success of high-dose bicalutamide (for 24 months) when combined with salvage external radiation therapy (XRT), while using a newer more potent anti-androgen for a shorter duration of time (6 months) in an effort to minimize adverse effects.

Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Prostate Drug: Enzalutamide Radiation: SRT Phase 2

Detailed Description:

Enzalutamide is a second-generation androgen receptor signaling inhibitor that significantly prolongs survival in patients with metastatic castration-resistant prostate cancer who have received prior docetaxel chemotherapy 35,36. Enzalutamide has demonstrated activity in cells that overexpress the androgen receptor. Unlike previous androgen receptor blocker (ARB) agents, Enzalutamide does not display any agonist properties and blocks translocation of the ligand-receptor complex into the nucleus preventing DNA binding 33. Enzalutamide is an oral agent that is generally well tolerated and does not require concurrent steroid administration, which makes it an ideal candidate for combination with salvage radiation therapy (SRT).

Finally, provocative preliminary Phase II data presented at the American Society of Clinical Oncology (ASCO) 2013 by M. Smith and colleagues assessed the efficacy and safety of 25-weeks (~6-mos) of enzalutamide alone in prostate cancer of all stages who had never received hormone therapy; presenting with non-castrate testosterone levels ( 230 ng/dL). Enzalutamide alone for 6-mos achieved a high PSA response rate with efficacy similar to castration, but .in contrast to castration, bone mineral density (BMD) remained stable and metabolic variables were not substantially impacted.

The trial described here differs from Radiation Therapy Oncology Group (RTOG) 96-01, RTOG 05-34 and RADICALS in several ways. First, the eligibility criteria are stricter; less favorable patients have been selected. Second, short-term ARB is being tested, while in RTOG 96-01 and RADICALS long-term ARB of 2-years was examined. Finally, and most importantly, we are testing the second generation ARB agent, enzalutamide, alone in combination with SRT as opposed to RTOG 05-34 and RADICALS which use androgen deprivation (AD).

This trial is not intended to address the efficacy of SRT alone over observation. The complete response rate (a drop in PSA to undetectable levels) after SRT is 70%-80% and durable responses are observed in 30%-40% of patients. For these reasons, it is not feasible or appropriate to randomize men between observation and SRT. The more important issue is whether the proportion of durable responses is increased by altering the therapeutic approach, such as the use of enhanced ARB using enzalutamide.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Phase II Randomized Placebo-Controlled Double-Blind Study of Salvage Radiation Therapy (SRT) Plus Placebo Versus SRT Plus Enzalutamide in Men With High-Risk PSA-Recurrent Prostate Cancer After Radical Prostatectomy
Actual Study Start Date : March 28, 2015
Actual Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: SRT plus Enzalutamide
Arm 2 (experimental): (SRT) Salvage radiation therapy (Three dimensional conformal radiation therapy (3D-CRT)/IMRT [Intensity-modulated radiation therapy]) 66.6-70.2 Gy as 1.8 Gy M-F for 37-39 fx PLUS Enzalutamide (MDV3100) 160 mg PO once daily for 6 months (2 months prior to SRT, 2 months during SRT and 2 months following SRT)
Drug: Enzalutamide
Enzalutamide (MDV3100) 160 mg PO once daily for 6 months (2 months prior to SRT, 2 months during SRT and 2 months following SRT)
Other Name: XTANDI

Placebo Comparator: SRT plus placebo
Arm 1 (control): Salvage radiation therapy (3D-CRT (Three dimensional conformal radiation therapy)/IMRT (Intensity-modulated radiation therapy)) 66.6-70.2 Gy given 1.8 Gy M-F for 37 -39 fx PLUS Placebo PO daily for 6 months (2 months prior to SRT, 2 months during SRT and 2 months following SRT)
Radiation: SRT
Salvage radiation therapy (3D-CRT (Three dimensional conformal radiation therapy)/IMRT) 66.6-70.2 Gy given 1.8 Gy M-F for 37 -39 fx
Other Name: Salvage Radiation Therapy

Primary Outcome Measures :
  1. Freedom of PSA (Prostate Specific Antigen) progression [ Time Frame: 2 years from end of therapy ]
    The primary efficacy endpoint is the rate of Freedom-from-PSA-progression (FFPP) at 2-years. FFPP is defined as the time from randomization to the date of PSA progression. A subject who does not have PSA progression at the time of the analysis will be censored at the last date of PSA measurement.

Secondary Outcome Measures :
  1. Local recurrence [ Time Frame: 2 years from end of therapy ]
    Local recurrence within the radiation field (confirmed pathologically) at 2-years

  2. Metastatic free survival rate [ Time Frame: 2 years from the time of registration ]
    Metastasis-free survival (MFS) rates at 2 years. Metastasis-free survival will be defined as the time from the date of registration to date of evidence of systemic disease on bone scan or cross sectional imaging or death, which occurs first.

  3. Adverse Events Encountered [ Time Frame: At the end of therapy at months 2, 3, 4, 5, 6 and then every 3 months for 24 months ]
    Safety as assessed by NCI Common Toxicity Scales (v4.0)

  4. How well participants tolerate treatment [ Time Frame: During active treatment phase of study, at the end of therapy at months 2, 3, 4, 5, 6 and then every 3 months for 24 months ]
    Quality of life (QoL) tools to be used to determine participant tolerability of treatment will include FACT-P, European Organization for the Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) -C30/QLQ-PR25, and SHIM.

  5. Feasibility of achieving stated accrual [ Time Frame: During active treatment phase of study, at the end of therapy at months 2, 3, 4, 5, 6 and then every 3 months for 24 months ]
    Compare anticipated accrual versus actual.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Willing and able to provide written informed consent and Health Insurance Portability and Accountability Act (HIPPA) authorization for the release of personal health information.
  • Males aged 18 years of age and above
  • Patients must have adenocarcinoma of the prostate gland
  • Patients must have received primary treatment with radical prostatectomy.
  • Patients must have evidence of biochemical (PSA) relapse after prostatectomy
  • Patients must have PSA within study range
  • Patients must have non-metastatic (M0) disease, as defined by a lack of metastases seen on CT scan of the chest/abdomen/pelvis and whole-body radionuclide 99Technetium (Tc) bone scan, (or sodium fluoride PET scan) taken within 3 months of study entry.
  • Patients must have had node negative (pN0) disease found at the time of surgery.
  • Patients must have non-castrate levels of serum testosterone levels within study range.
  • Patients must not have previously received hormonal therapy (LHRH agonist, antiandrogen, or both), with the exception of neoadjuvant or adjuvant hormones given in conjunction with prostatectomy.
  • Patients must have Eastern Cooperative Oncology Group (ECOG)performance status of 0-1, and life expectancy greater 3 years.
  • Patients must have laboratory test results within the certain ranges
  • Patients must be disease-free from prior malignancies for greater than 3 years, with the exception of non-melanoma skin cancers and superficial urothelial cancers.
  • Patients must have the ability to swallow the study drug whole as a tablet or capsule.
  • Throughout study, male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration or per local guidelines where these require additional description of contraceptive methods.
  • Throughout the study, patients must use a condom if having sex with a pregnant woman.

Exclusion Criteria:

  • Currently active second malignancy
  • Primary treatment with radiation therapy.
  • Radiographic or clinical evidence of local-regional tumor recurrence,
  • Concurrent use of other antiandrogens, estrogen-like agents, or 5a-reductase inhibitors.
  • Use of systemic corticosteroids equivalent to prednisone (inhaled corticosteroids are permitted).
  • Concurrent use of other anti-cancer agents or treatments.
  • Serious concurrent medical illnesses (including uncontrolled major cardiac, pulmonary, Child-Pugh C liver or psychiatric diseases) or active major infections (including HIV, Hepatitis A-C).
  • Clinically significant cardiovascular disease including:

    • Myocardial infarction within 6 months of Screening visit.
    • Uncontrolled angina within 3 months of Screening visit.
    • Congestive heart failure (within certain ranges)
    • History of clinically significant ventricular arrhythmias
    • Prolonged corrected QT interval
    • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
    • Hypotension within certain ranges
    • Uncontrolled hypertension within certain ranges
  • Medications which lowers seizure threshold.
  • History of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Also, history of loss of consciousness or transient ischemic attack within 12months of enrollment (Day 1 visit).
  • Patients taking medications that may have adverse interactions with enzalutamide

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02203695

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United States, District of Columbia
Sibley Memorial Hospital
Washington, District of Columbia, United States, 20016
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana University
Lafayette, Indiana, United States, 47904
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21287
Suburban Hospital
Bethesda, Maryland, United States, 20814
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Center
Detroit, Michigan, United States, 48201
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Utah
University of Utah - Huntsman Cancer Center
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Astellas Pharma Inc
Medivation, Inc.
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Principal Investigator: Phuoc Tran, M.D. The SKCCC at Johns Hopkins
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT02203695    
Other Study ID Numbers: J1454
IRB00030471 ( Other Identifier: JHMIRB )
First Posted: July 30, 2014    Key Record Dates
Last Update Posted: May 31, 2023
Last Verified: May 2023
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Salvage Radiation Therapy (SRT)
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type