Clinical Trials /

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

NCT02543255

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Anti-Androgens and Cabazitaxel in Defining Complete Response in Prostatectomy (ACDC Trial)
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 15-051
  • NCT ID: NCT02543255

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
Abiraterone acetate with prednisoneAbiraterone acetate + prednisone + leuprolide + cabazitaxel
LeuprolideAbiraterone acetate + prednisone + leuprolide + cabazitaxel
Cabazitaxel with peg-filgrastimAbiraterone acetate + prednisone + leuprolide + cabazitaxel

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Abiraterone acetate + prednisone + leuprolide + cabazitaxelExperimentalParticipants 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.
  • Abiraterone acetate with prednisone
  • Leuprolide
  • Cabazitaxel with peg-filgrastim
Abiraterone acetate + prednisone + leuprolideActive ComparatorParticipants 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.
  • Abiraterone acetate with prednisone
  • Leuprolide

Eligibility Criteria

        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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathological complete response
Time Frame:24 weeks from start of treatment.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pre-operative PSA levels
Time Frame:24 weeks of treatment
Safety Issue:
Description:The effect of neoadjuvant leuprolide, and abiraterone acetate and prednisone with and without cabazitaxel on pre-operative PSA will be evaluated.
Measure:Mean nadir PSA levels
Time Frame:24 weeks of treatment
Safety Issue:
Description:The effect of neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel on mean nadir PSA levels will be evaluated.
Measure:Percentage of participants achieving a PSA < 0.2 ng/mL
Time Frame:24 weeks of treatment
Safety Issue:
Description: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.
Measure:Percentage of participants achieving a 50 and 90% decrease in PSA levels
Time Frame:up to 24 weeks of treatment
Safety Issue:
Description: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.
Measure:Rate of positive surgical margins
Time Frame:up to 24 weeks of treatment
Safety Issue:
Description:The rate of positive surgical margins following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
Measure:Rate of near-complete response (<5 mm tumour)
Time Frame:up to 24 weeks of treatment
Safety Issue:
Description: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.
Measure:Rate of extracapsular extension
Time Frame:up to 24 weeks of treatment
Safety Issue:
Description:The rate of extracapsular extension following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
Measure:Rate of positive seminal vesicle involvement
Time Frame:up to 24 weeks of treatment
Safety Issue:
Description:The rate of positive seminal vesicle involvement following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
Measure:Rate of nodal involvement
Time Frame:up to 24 weeks of treatment
Safety Issue:
Description:The rate of nodal involvement following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
Measure:Tumour proliferation (Ki-67 index)
Time Frame:up to 24 weeks of treatment
Safety Issue:
Description:Tumour proliferation, indexed using Ki-67 immunohistochemistry, following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel will be evaluated.
Measure:Androgen receptor expression
Time Frame:up to 24 weeks of treatment
Safety Issue:
Description:Androgen receptor expression will be evaluated using immunohistochemistry following treatment with neoadjuvant leuprolide, abiraterone acetate, and prednisone with and without cabazitaxel.
Measure:Incidence of adverse events
Time Frame:up to 24 weeks of treatment
Safety Issue:
Description:Incidence of adverse events will be evaluated for the duration of the study.
Measure:Severity of adverse events
Time Frame:Aup to 24 weeks of treatment
Safety Issue:
Description:Severity of adverse events will be evaluated for the duration of the study.
Measure:Androgen levels (if optional biopsy tissue is available)
Time Frame:up to 24 weeks of treatment
Safety Issue:
Description:If the participants agrees to optional pre-treatment biopsy, androgen levels will be compared between the pre-treatment tissue samples and prostatectomy tissue.
Measure:Genomic alterations between pre- and post-treatment tissue
Time Frame:up to 24 weeks of treatment
Safety Issue:
Description:If the participants agrees to optional pre-treatment biopsy, genomic alterations between the pre-treatment tissue samples and prostatectomy tissue will be evaluated.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University Health Network, Toronto

Trial Keywords

  • High risk

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