A Study of Salvage Radiotherapy With or Without Enzalutamide in Recurrent Prostate Cancer Following Surgery

PRIMARY OBJECTIVE:

To determine whether, in men with post-prostatectomy PSA (prostate specific antigen) recurrences with aggressive disease features, salvage radiotherapy (SRT) with enhanced androgen deprivation therapy (ADT), consisting of enzalutamide (MDV3100) and a GnRH analog, will improve progression-free survival compared to SRT with standard GnRH analog -based ADT.

• Radiation: Radiation Therapy
  Radiation Therapy
  Other Names:

  • RT
  • Three-Dimensional Conformal Radiation Therapy (3D-CRT)
  • Intensity-Modulated Radiation Therapy (IMRT)
  • Image-Guided Radiation Therapy (IGRT)
  • Radiotherapy
• Drug: Enzalutamide
  Anti-androgen
  Other Name: Xtandi®
• Drug: Bicalutamide
  Anti-androgen
  Other Name: Casodex®
• Drug: GnRH analog
  Anti-androgen
  Other Names:

  • Gonadotropin-releasing hormone analog
  • Lupron®
  • leuprolide acetate
  • goserelin acetate
  • Eligard?
  • Viadur?
  • Zoldaex®
  • Trelstar®

• Active Comparator: Salvage Radiation Therapy + Standard ADT
  Salvage RT will be given up to 66.60 Gy along with 24 months of a GnRH analog with or without 1-4 months of bicalutamide.
  Interventions:

  • Radiation: Radiation Therapy
  • Drug: Bicalutamide
  • Drug: GnRH analog
• Experimental: Salvage Radiation Therapy + Enhanced ADT
  Salvage RT will be given up to 66.60 Gy along with 24 months of a GnRH analog + 24 months of enzalutamide.
  Interventions:

  • Radiation: Radiation Therapy
  • Drug: Enzalutamide
  • Drug: GnRH analog

Inclusion Criteria:

• Pathologically (histologically) proven adenocarcinoma confirmed by prostatectomy performed within 10 years prior to registration and any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted.
• PSA level (? 0.7 ng/mL) within 90 days prior to registration. GnRH analog may be started no more than 42 days prior study entry, but patients must have a PSA ? 0.7 ng/mL prior to starting ADT.
• Hemoglobin ? 9.0 g/dL, independent of transfusion and/or growth factors within 90 days prior to registration.
• Platelet count ? 75,000 x 109/µL independent of transfusion and/or growth factors within 90 days prior to registration.

• At least 1 of the following aggressive features:

  • Gleason score of 8-10 (note any Gleason score is eligible)

  • Seminal vesicle invasion (SVI) (note any pT stage [AJCC v8.0] is eligible but a pT stage

    ? pT3b is considered aggressive)

  • Locoregional node involvement at radical prostatectomy (pN1)
  • Persistently elevated PSA post-RP nadir (PEPP) defined as PSA > 0.1 ng/mL after radical prostatectomy
• Serum albumin ? 3.0 g/dL within 90 days prior to registration
• GFR >35 mL/min estimated by Cockcroft-Gault or measured directly by 24 hour urine creatinine within 90 days prior to registration.
• Serum total bilirubin ?1.5 × ULN (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ?1.5 × ULN, subject is eligible) within 90 days prior to registration.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN within 90 days prior to registration.
• Testosterone >50 ng/dL within 90 days prior to registration. Prior androgen deprivation (GnRH analog and/or non-steroidal antiandrogen) therapy is allowed provided that serum testosterone concentration must be ? 50 ng/dL prior to registration or starting ADT, whichever occurs first; 5-alpha reductase inhibitors will not impact eligibility, but must be discontinued prior to starting protocol treatment.
• History and physical with ECOG Performance Status 0-1 or within 90 days prior to registration.

Exclusion Criteria:

• Definitive clinical or radiologic evidence of metastatic disease with the exception of locoregional lymph nodes.
• Prior invasive malignancy (except non-melanomatous skin cancer carcinoma in situ of the male breast, penis, oral cavity, or stage Ta of the bladder, or stage I completely resected melanoma) unless disease free for a minimum of 2 years).
• Prior systemic chemotherapy for the study cancer. Note: prior chemotherapy for a different cancer is allowable.
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.

• History of any of the following:

  • Documented inflammatory bowel disease
  • Transmural myocardial infarction within the last 4 months prior to registration.
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 4 months prior to registration
  • Seizure disorder or condition that may predispose to seizure (e.g. prior cortical stroke or significant brain trauma)
  • Uncontrolled hypertension defined as a sustained systolic blood pressure in excess of 150 mmHg or a sustained diastolic blood pressure in excess of 90 mmHg despite optimized antihypertensive therapy.
• Known gastrointestinal disorder affecting absorption of oral medications.
• Active uncontrolled infection defined as an identified infectious condition that requires active therapy that has not yet been completed.
• HIV positive patients with CD4 count < 200 cells/microliter within 30 days prior to registration OR HIV patients under treatment with highly active antiretroviral therapy (HAART) within 30 days prior to registration regardless of CD4 count. Note: HIV testing is not required for eligibility for this protocol as it is self-reported. This exclusion criterion is necessary because the treatments involved in this protocol may be immunosuppressive and/or interact with HAART.

• Pfizer
• Astellas Pharma Inc