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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 : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Abiraterone acetate with prednisone Drug: Leuprolide Drug: Cabazitaxel with peg-filgrastim Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 2016
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids

Arm Intervention/treatment
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.
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.

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.
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.




Primary Outcome Measures :
  1. Pathological complete response [ Time Frame: 24 weeks from start of treatment. ]

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02543255


Contacts
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Contact: Miran Kenk 416-946-4501 ext 3431 miran.kenk@uhn.ca

Locations
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Canada, British Columbia
The Prostate Centre Not yet recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Principal Investigator: Kim Chi, MD         
Canada, Ontario
Juravinski Cancer Centre Not yet recruiting
Hamilton, Ontario, Canada, L8V 5C2
Principal Investigator: Hotte Sebastien, MD, MSc, FRCPC         
London Health Sciences Centre Recruiting
London, Ontario, Canada, N6A 5W9
Principal Investigator: Joseph Chin, MD, FRCSC         
Sunnybrook Health Sciences Centre Not yet recruiting
Toronto, Ontario, Canada, M4N 3M5
Principal Investigator: Urban Emmenegger, MD         
University Health Network, Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Miran Kenk    416-946-4501 ext 3431    miran.kenk@uhn.ca   
Principal Investigator: Neil Fleshner         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
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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

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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02543255     History of Changes
Other Study ID Numbers: 15-051
First Posted: September 7, 2015    Key Record Dates
Last Update Posted: April 10, 2019
Last Verified: April 2019

Keywords provided by University Health Network, Toronto:
High risk

Additional relevant MeSH terms:
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Prednisone
Leuprolide
Abiraterone Acetate
Androgens
Androgen Antagonists
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents