Randomized Salvage Radiation Therapy Plus Enzalutamide Post Prostatectomy

NCT02203695 | Completed Phase 2 Results DMC

• 2 other identifiers: J1454IRB00030471
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 9

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.

Conditions

Adenocarcinoma of the Prostate

Keywords

Salvage Radiation Therapy (SRT); Enzalutamide

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With Freedom of PSA (Prostate Specific Antigen) Progression

  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.

  From time of randomization to date of PSA progression, approximately 2 years.

Secondary Outcomes (7)

• Number of Participants With Local Recurrence

  2 years from end of radiation therapy

• Metastatic Free Survival Rate

  2 years from the time of registration

• How Well Participants Tolerate Treatment Assessed by European Organization for Research & Treatment of Cancer Quality of Life (Questionnaire (EORTC-QLQ-P25)

  Baseline, End of Treatment (180 Days) and 6 Months Post-treatment

• How Well Participants Tolerate Treatment Assessed by the Functional Assessment of Cancer Therapy-Prostate (FACT-P).

  Baseline, End of Treatment (180 Days) and 6 Months Post-treatment

• How Well Participants Tolerate Treatment Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).

  Baseline, End of Treatment (180 Days) and 6 Months Post-treatment

Study Arms (2)

SRT plus Enzalutamide

EXPERIMENTAL

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

SRT plus placebo

PLACEBO COMPARATOR

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

Interventions

Enzalutamide DRUG

Enzalutamide (MDV3100) 160 mg PO once daily for 6 months (2 months prior to SRT, 2 months during SRT and 2 months following SRT)

Also known as: XTANDI

SRT plus Enzalutamide

SRT RADIATION

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

Also known as: Salvage Radiation Therapy

SRT plus placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Astellas Pharma Inc: collaborator
• Medivation, Inc.: collaborator

Study Sites (9)

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indiana University

Lafayette, Indiana, 47904, United States

Location

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Suburban Hospital

Bethesda, Maryland, 20814, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

University of Utah - Huntsman Cancer Center

Salt Lake City, Utah, 84112, United States

Location

Related Publications (2)

• Tran PT, Lowe K, Tsai HL, Song DY, Hung AY, Hearn JWD, Miller S, Proudfoot JA, Deek MP, Phillips R, Lotan T, Paller CJ, Marshall CH, Markowski M, Dipasquale S, Denmeade S, Carducci M, Eisenberger M, DeWeese TL, Orton M, Deville C, Davicioni E, Liauw SL, Heath EI, Greco S, Desai NB, Spratt DE, Feng F, Wang H, Beer TM, Antonarakis ES. Phase II Randomized Study of Salvage Radiation Therapy Plus Enzalutamide or Placebo for High-Risk Prostate-Specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy: The SALV-ENZA Trial. J Clin Oncol. 2023 Feb 20;41(6):1307-1317. doi: 10.1200/JCO.22.01662. Epub 2022 Nov 11.

  PMID: 36367998 DERIVED

• Kapoor R, Deek MP, McIntyre R, Raman N, Kummerlowe M, Chen I, Gaver M, Wang H, Denmeade S, Lotan T, Paller C, Markowski M, Carducci M, Eisenberger M, Beer TM, Song DY, DeWeese TL, Hearn JW, Greco S, DeVille C, Desai NB, Heath EI, Liauw S, Spratt DE, Hung AY, Antonarakis ES, Tran PT. A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA). BMC Cancer. 2019 Jun 13;19(1):572. doi: 10.1186/s12885-019-5805-z.

  PMID: 31196032 DERIVED

MeSH Terms

Interventions

enzalutamide

Results Point of Contact

• Title: Dr. Daniel Song
• Organization: Johns Hopkins University, School of Medicine

dsong2@jh.edu

410-502-5875

Study Officials

• Daniel Song, M.D.

  The SKCCC at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2014
• First Posted: July 30, 2014
• Study Start: March 28, 2015
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: October 28, 2025
• Results First Posted: October 24, 2025

Record last verified: 2025-10

Locations

US (9)