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

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

Study Description

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

Study Design

• 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 2020
• Estimated Study Completion Date: August 2020

Arms and Interventions

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.

Outcome Measures

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.

Eligibility Criteria

• 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).

Contacts and Locations

Contacts

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

Locations

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

• 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

More Information

• Responsible Party: University Health Network, Toronto
• ClinicalTrials.gov Identifier: NCT02543255
• Other Study ID Numbers: 15-051
• First Posted: September 7, 2015
• Last Update Posted: January 13, 2020
• Last Verified: January 2020

Keywords provided by University Health Network, Toronto:

High risk

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Prednisone; Leuprolide; Abiraterone Acetate; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Fertility Agents, Female; Fertility Agents; Reproductive Control Agents; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors