A Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer

Overview

About this study

This is a randomized, open-label, three-arm, phase 3 study in men with biochemically recurrent prostate cancer and PSA doubling time ≤ 9 months at the time of study entry.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Histologically confirmed prostate adenocarcinoma.
  • Prior radical prostatectomy.
  • Biochemically recurrent prostate cancer with PSA doubling time ≤ 9 months at the time of study entry. Calculation of PSA doubling time should include the use of all available PSA values obtained within past 12 months prior to randomization, with a minimum of 3 values separated by at least 2 weeks apart. PSA values obtained prior to localized therapy will be excluded. PSA doubling time to be estimated using Memorial Sloan Kettering Cancer Center online calculator (https://www.mskcc.org/nomograms/prostate/psa-doubling-time).
  • Prior adjuvant or salvage radiation or not a candidate for radiation based upon clinical assessment of disease characteristics and patient co-morbidities.
  • Screening PSA > 0.5 ng/mL
  • No definitive evidence of metastases on screening CT or MRI of abdomen/pelvis and radionuclide whole body bone scan per the judgment of the investigator. Abdominal and/or pelvic lymph nodes measuring 2 cm or less in short axis diameter are allowed. Lesions identified on other imaging modalities (e.g., PSMA or choline PET) that are not visualized on CT and/or MRI or radionuclide bone scan are allowed. Equivocal lesions on bone scan should be followed up with additional imaging as clinically indicated.
  • Screening serum testosterone > 150 ng/dL.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status grade 0 or 1 or Karnofsky Performance Status ≥ 70.
  • Age ≥ 18 years old.
  • Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to Cycle 1 Day 1.
  • Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.
  • Adequate organ function as defined by the following laboratory values at screening:
    • Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) < 2.5 x upper limit of normal (ULN);
    • Total serum bilirubin ≤ 1.5 x ULN. 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 may be eligible);
    • Serum potassium ≥ 3.5 mmol/L. Supplementation and re-screening is allowed;
    • Estimated creatinine clearance > 45 ml/min using Cockroft-Gault equation;
    • Platelets ≥ 100,000/microliter independent of transfusion and/or growth factors within 3 months prior to randomization;
    • Hemoglobin ≥ 9.0 g/dL independent of transfusion and/or growth factors within 3 months prior to randomization;
    • Serum albumin ≥ 3.0 g/dL.

Exclusion Criteria:

  • Prior systemic treatment with androgen deprivation therapy and/or first-generation anti-androgen (e.g., bicalutamide, nilutamide, flutamide) for biochemically recurrent prostate cancer. Prior ADT and/or first-generation anti-androgen in the (neo)adjuvant and/or salvage setting in conjunction with radiation or surgery is allowed provided last effective dose of ADT and/or first-generation anti- androgen is > 9 months prior to date of randomization and total duration of prior therapy is ≤ 36 months.
  • Prior treatment with CYP17 inhibitor (e.g., ketoconazole, abiraterone acetate, galeterone) or  next generation androgen receptor antagonist including apalutamide or enzalutamide.
  • Prior chemotherapy for prostate cancer except if administered in neoadjuvant or adjuvant setting.
  • Use of 5-alpha reductase inhibitor within 42 days prior to randomization.
  • Use of investigational agent within 28 days prior to randomization.
  • Use of other prohibited medications within 7 days prior to Cycle 1 Day 1 on study (Arms B and C only).
  • Prior bilateral orchiectomy.
  • Seizure or known condition that may pre-dispose to seizure (e.g., prior stroke within 1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy).
  • Uncontrolled hypertension.
  • Gastrointestinal disorder affecting absorption or the ability to swallow tablets.
  • Baseline severe hepatic impairment (Child-Pugh Class B & C).
  • Intercurrent illness that is not controlled such as active infection, psychiatric illness/social situations that would limit compliance with study requirements.
  • Any chronic medical condition requiring a higher dose of corticosteroid than equivalent of 10 mg prednisone/prednisolone per day.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Alan Bryce, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

  • It has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours. Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 WHO classification. In most cases, it represents intraductal spread of aggressive prostatic carcinoma and should be separated from high-grade prostatic intraepithelial neoplasia. New acinar adenocarcinoma variants are microcystic adenocarcinoma and pleomorphic giant cell adenocarcinoma. Modifications to the Gleason grading system are incorporated into the 2016 WHO section on grading of prostate cancer, and it is recommended that the percentage of pattern 4 should be reported for Gleason score 7. The new WHO classification further recommends the recently developed prostate cancer grade grouping with five grade groups. For bladder cancer, the 2016 WHO classification continues to recommend the 1997 International Society of Urological Pathology grading classification. Newly described or better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential, which is frequently identified in patients with a prior history of urothelial carcinoma. Invasive urothelial carcinoma with divergent differentiation refers to tumours with some percentage of "usual type" urothelial carcinoma combined with other morphologies. Pathologists should mention the percentage of divergent histologies in the pathology report. Read More on PubMed
  • This study aimed to investigate the role of AR-V7 in development of castration-resistant prostate cancer (CRPC) and to determine whether the AR-V7 expression in CRPC tissues can predict cancer-specific survival. We enrolled 100 localized prostate cancer (PCa) (cohort 1), 104 newly diagnosed metastatic PCa (cohort 2), and 46 CRPC (cohort 3) patients treated at our institution. The expression of AR-V7 in PCa was assessed by immunohistochemistry. Cox regression models were used to evaluate the predictive role of all covariates for the development of CRPC in cohort 2 and for cancer-specific survival in cohort 3. Time to CRPC and cancer-specific survival curves were estimated using the Kaplan-Meier method. AR-V7 expression rate in cohort 3 was significantly elevated compared with other two cohorts (p < 0.001). Multivariate analysis revealed that AR-V7 was an independent predictive factor for CRPC development (HR = 2.627, p = 0.001) and for cancer specific survival (HR = 2.247, p = 0.033). Furthermore, the AR-V7 expression was associated with shorter survival in CRPC patients. Our results demonstrated protein AR-V7 levels in primary tumors can be used as a predictive marker for the development of CRPC and as a prognostic factor in CRPC patients. Therapy targeting AR-V7 may help prevent PCa progression and improve the prognosis of CRPC patients. Read More on PubMed
  • The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed as one of the first projects funded by the NIH Roadmap for Medical Research Initiative to re-engineer the clinical research enterprise. The primary goal of PROMIS is to build item banks and short forms that measure key health outcome domains that are manifested in a variety of chronic diseases which could be used as a "common currency" across research projects. To date, item banks, short forms and computerized adaptive tests (CAT) have been developed for 13 domains with relevance to pediatric and adult subjects. To enable easy delivery of these new instruments, PROMIS built a web-based resource (Assessment Center) for administering CATs and other self-report data, tracking item and instrument development, monitoring accrual, managing data, and storing statistical analysis results. Assessment Center can also be used to deliver custom researcher developed content, and has numerous features that support both simple and complicated accrual designs (branching, multiple arms, multiple time points, etc.). This paper provides an overview of the development of the PROMIS item banks and details Assessment Center functionality. Read More on PubMed
  • To identify predictors of distant metastases (DM) among patients who develop an isolated prostate-specific antigen (PSA) relapse after definitive external-beam radiotherapy for clinically localized prostate cancer. Read More on PubMed
  • We determine the efficacy of conventional dose, external beam radiation for localized prostate cancer using cohort analysis with maximized followup. Read More on PubMed
  • Each year the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute (Surveillance, Epidemiology, and End Results [SEER] Program), the Centers for Disease Control and Prevention (National Program of Cancer Registries), and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. A total of 1,658,370 new cancer cases and 589,430 cancer deaths are projected to occur in the United States in 2015. During the most recent 5 years for which there are data (2007-2011), delay-adjusted cancer incidence rates (13 oldest SEER registries) declined by 1.8% per year in men and were stable in women, while cancer death rates nationwide decreased by 1.8% per year in men and by 1.4% per year in women. The overall cancer death rate decreased from 215.1 (per 100,000 population) in 1991 to 168.7 in 2011, a total relative decline of 22%. However, the magnitude of the decline varied by state, and was generally lowest in the South (∼15%) and highest in the Northeast (≥20%). For example, there were declines of 25% to 30% in Maryland, New Jersey, Massachusetts, New York, and Delaware, which collectively averted 29,000 cancer deaths in 2011 as a result of this progress. Further gains can be accelerated by applying existing cancer control knowledge across all segments of the population. Read More on PubMed
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CLS-20403514

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