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Anti-Androgens and Cabazitaxel in Defining Complete Response in Prostatectomy (ACDC Trial) (ACDC-RP)

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ClinicalTrials.gov Identifier: NCT02543255
Recruitment Status : Recruiting
First Posted : September 7, 2015
Last Update Posted : January 13, 2020
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE September 3, 2015
First Posted Date  ICMJE September 7, 2015
Last Update Posted Date January 13, 2020
Actual Study Start Date  ICMJE September 2016
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 4, 2015)
Pathological complete response [ Time Frame: 24 weeks from start of treatment. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2015)
  • Pre-operative PSA levels [ Time Frame: 24 weeks of treatment ]
    The effect of neoadjuvant leuprolide, and abiraterone acetate and prednisone with and without cabazitaxel on pre-operative PSA will be evaluated.
  • Mean nadir PSA levels [ Time Frame: 24 weeks of treatment ]
    The effect of neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel on mean nadir PSA levels will be evaluated.
  • Percentage of participants achieving a PSA < 0.2 ng/mL [ Time Frame: 24 weeks of treatment ]
    The percentage of participants achieving a PSA < 0.2 ng/mL following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
  • Percentage of participants achieving a 50 and 90% decrease in PSA levels [ Time Frame: up to 24 weeks of treatment ]
    The percentage of participants achieving a 50 and 90% decrease in PSA levels following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
  • Rate of positive surgical margins [ Time Frame: up to 24 weeks of treatment ]
    The rate of positive surgical margins following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
  • Rate of near-complete response (<5 mm tumour) [ Time Frame: up to 24 weeks of treatment ]
    The rate of near-complete response (<5 mm tumour) following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
  • Rate of extracapsular extension [ Time Frame: up to 24 weeks of treatment ]
    The rate of extracapsular extension following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
  • Rate of positive seminal vesicle involvement [ Time Frame: up to 24 weeks of treatment ]
    The rate of positive seminal vesicle involvement following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
  • Rate of nodal involvement [ Time Frame: up to 24 weeks of treatment ]
    The rate of nodal involvement following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
  • Tumour proliferation (Ki-67 index) [ Time Frame: up to 24 weeks of treatment ]
    Tumour proliferation, indexed using Ki-67 immunohistochemistry, following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
  • Androgen receptor expression [ Time Frame: up to 24 weeks of treatment ]
    Androgen receptor expression will be evaluated using immunohistochemistry following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel.
  • Incidence of adverse events [ Time Frame: up to 24 weeks of treatment ]
    Incidence of adverse events will be evaluated for the duration of the study.
  • Severity of adverse events [ Time Frame: Aup to 24 weeks of treatment ]
    Severity of adverse events will be evaluated for the duration of the study.
  • Androgen levels (if optional biopsy tissue is available) [ Time Frame: up to 24 weeks of treatment ]
    If the participants agrees to optional pre-treatment biopsy, androgen levels will be compared between the pre-treatment tissue samples and prostatectomy tissue.
  • Genomic alterations between pre- and post-treatment tissue [ Time Frame: up to 24 weeks of treatment ]
    If the participants agrees to optional pre-treatment biopsy, genomic alterations between the pre-treatment tissue samples and prostatectomy tissue will be evaluated.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anti-Androgens and Cabazitaxel in Defining Complete Response in Prostatectomy (ACDC Trial)
Official Title  ICMJE Anti-Androgens and Cabazitaxel in Defining Complete Response in Prostatectomy (ACDC-RP Trial): A Randomized, Open-label, Multi-centre Phase-2 Study Evaluating the Pathological Complete Response (pCR) Rate Following Neoadjuvant Therapy in Participants With High-risk Prostate Carcinoma for Whom Radical Prostatectomy is Indicated
Brief Summary This study evaluates the use of chemotherapy with cabazitaxel in addition to abiraterone acetate, prednisone, and leuprolide in neoadjuvant setting prior to radical prostatectomy in patients with high-risk prostate carcinoma. Half of the participants will receive treatment with abiraterone acetate, prednisone, leuprolide, and cabazitaxel, while the other half will receive only abiraterone acetate, prednisone, and leuprolide.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: Abiraterone acetate with prednisone
    Abiraterone acetate will be administered orally as a tablet at 1000 mg/day with prednisone (5 mg oral tablet, twice daily) for 24 weeks.
  • Drug: Leuprolide
    Leuprolide will be administered by subcutaneous injection at 22.5 mg dose every 12 weeks for 24 weeks.
  • Drug: Cabazitaxel with peg-filgrastim
    Cabazitaxel will be administered in 6 cycles, with 20 mg/m2 per cycle and 3 weeks between cycles.
Study Arms  ICMJE
  • Experimental: Abiraterone acetate + prednisone + leuprolide + cabazitaxel
    Participants randomized to this arm will receive abiraterone acetate (1000 mg/day), prednisone (5 mg twice daily), leuprolide (22.5 mg every 3 months), and cabazitaxel (20 mg/m2, with 6 mg pegfilgrastim administered 24 h following cabazitaxel) prior to radical prostatectomy.
    Interventions:
    • Drug: Abiraterone acetate with prednisone
    • Drug: Leuprolide
    • Drug: Cabazitaxel with peg-filgrastim
  • Active Comparator: Abiraterone acetate + prednisone + leuprolide
    Participants randomized to this arm will receive abiraterone acetate (1000 mg/day) , prednisone (5 mg twice daily), and leuprolide (22.5 mg every 3 months) prior to radical prostatectomy.
    Interventions:
    • Drug: Abiraterone acetate with prednisone
    • Drug: Leuprolide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 1, 2016)
76
Original Estimated Enrollment  ICMJE
 (submitted: September 4, 2015)
74
Estimated Study Completion Date  ICMJE August 2020
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Willing and able to provide informed consent;
  • Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features with a minimum of 3 cores positive for tumour;
  • Tumour biopsy tissue accessible for downstream evaluation;
  • Must be candidates for radical prostatectomy and considered surgically resectable by urologic evaluation;
  • High Risk D'Amico score defined as either PSA > 20, Gleason score ≥ 8 as determined by the local pathologist; or T2c-3 based on DRE, pathologic review +/- imaging;
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
  • No evidence of metastatic disease or nodal disease as determined by radionuclide bone scans and computed tomography (CT)/magnetic resonance imaging (MRI); non-pathological lymph nodes must be less than 15 mm in the short (transverse) axis;
  • Able to swallow the study drug(s) as prescribed and comply with study requirements;
  • Required initial laboratory values:
  • Absolute neutrophil count (ANC) ≥ 1500/μL;
  • Platelet count ≥ 100,000/μL;
  • Hemoglobin ≥ 90 g/L;
  • Creatinine ≤ 175 μmol/L;
  • Bilirubin ≤ upper limit of institutional normal (ULN);
  • AST/ALT ≤ 1.5 × ULN.

Exclusion Criteria:

  • Received an investigational agent within 4 weeks prior to screening;
  • Stage T4 prostate cancer by clinical examination or radiologic evaluation;
  • Hypogonadism or severe androgen deficiency as defined by screening serum testosterone below the normal range for the institution;
  • Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer;
  • Receiving concurrent androgens, estrogens, or progestational agents, or received any of these agents within the 6 months prior to randomization;
  • History of another malignancy within the previous 5 years other than curatively treated nonmelanomatous skin cancer and non-muscle invasive bladder cancer;
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiovascular disease, unstable angina pectoris, cardiac arrhythmia that is symptomatic or requires active therapy; deep venous thrombosis within 3 months prior to randomization;
  • Previous use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683, TAK-448) or targets the androgen receptor (e.g., enzalutamide, BMS 641988);
  • Liver injury or disease (e.g., viral hepatitis, liver failure Child-Pugh Class C).
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Miran Kenk 416-946-4501 ext 3431 miran.kenk@uhn.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02543255
Other Study ID Numbers  ICMJE 15-051
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Neil E Fleshner, MD, MPH, FRCSC University Health Network, Toronto
Principal Investigator: Anthony Joshua, BSc (Med), MBBS, PhD, FRACP University Health Network, Toronto
PRS Account University Health Network, Toronto
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP