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

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

Sponsors

Lead Sponsor: University Health Network, Toronto

Source 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.

Overall Status Recruiting
Start Date September 2016
Completion Date August 2020
Primary Completion Date August 2020
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Pathological complete response 24 weeks from start of treatment.
Secondary Outcome
Measure Time Frame
Pre-operative PSA levels 24 weeks of treatment
Mean nadir PSA levels 24 weeks of treatment
Percentage of participants achieving a PSA < 0.2 ng/mL 24 weeks of treatment
Percentage of participants achieving a 50 and 90% decrease in PSA levels up to 24 weeks of treatment
Rate of positive surgical margins up to 24 weeks of treatment
Rate of near-complete response (<5 mm tumour) up to 24 weeks of treatment
Rate of extracapsular extension up to 24 weeks of treatment
Rate of positive seminal vesicle involvement up to 24 weeks of treatment
Rate of nodal involvement up to 24 weeks of treatment
Tumour proliferation (Ki-67 index) up to 24 weeks of treatment
Androgen receptor expression up to 24 weeks of treatment
Incidence of adverse events up to 24 weeks of treatment
Severity of adverse events Aup to 24 weeks of treatment
Androgen levels (if optional biopsy tissue is available) up to 24 weeks of treatment
Genomic alterations between pre- and post-treatment tissue up to 24 weeks of treatment
Enrollment 76
Condition
Intervention

Intervention Type: Drug

Intervention Name: Abiraterone acetate with prednisone

Description: Abiraterone acetate will be administered orally as a tablet at 1000 mg/day with prednisone (5 mg oral tablet, twice daily) for 24 weeks.

Intervention Type: Drug

Intervention Name: Leuprolide

Description: Leuprolide will be administered by subcutaneous injection at 22.5 mg dose every 12 weeks for 24 weeks.

Intervention Type: Drug

Intervention Name: Cabazitaxel with peg-filgrastim

Description: Cabazitaxel will be administered in 6 cycles, with 20 mg/m2 per cycle and 3 weeks between cycles.

Arm Group Label: Abiraterone acetate + prednisone + leuprolide + cabazitaxel

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).

Gender: Male

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Overall Contact

Last Name: Miran Kenk

Phone: 416-946-4501

Phone Ext.: 3431

Email: [email protected]

Location
Facility: Status: Investigator:
The Prostate Centre | Vancouver, British Columbia, V5Z 1M9, Canada Not yet recruiting Kim Chi, MD Principal Investigator
Juravinski Cancer Centre | Hamilton, Ontario, L8V 5C2, Canada Not yet recruiting Hotte Sebastien, MD, MSc, FRCPC Principal Investigator
London Health Sciences Centre | London, Ontario, N6A 5W9, Canada Recruiting Joseph Chin, MD, FRCSC Principal Investigator
Sunnybrook Health Sciences Centre | Toronto, Ontario, M4N 3M5, Canada Not yet recruiting Urban Emmenegger, MD Principal Investigator
University Health Network, Princess Margaret Cancer Centre | Toronto, Ontario, M5G 2M9, Canada Recruiting Miran Kenk 416-946-4501 3431 [email protected] Neil Fleshner Principal Investigator
Location Countries

Canada

Verification Date

January 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Abiraterone acetate + prednisone + leuprolide + cabazitaxel

Type: Experimental

Description: 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.

Label: Abiraterone acetate + prednisone + leuprolide

Type: Active Comparator

Description: 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.

Acronym ACDC-RP
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov