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

Prostate Cancer Clinical Trial

— ACDC-RP  

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 Details — Status: Completed

Administrative data

• NCT number: NCT02543255
• Other study ID #: 15-051
• Status: Completed
• Phase: Phase 2
• Start date: September 2016
• Est. completion date: July 20, 2021

Study information

• Verified date: January 2024
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: July 20, 2021
• Est. primary completion date: May 27, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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.
• Leuprolide
Leuprolide will be administered by subcutaneous injection at 22.5 mg dose every 12 weeks for 24 weeks.
• Cabazitaxel with peg-filgrastim
Cabazitaxel will be administered in 6 cycles, with 20 mg/m2 per cycle and 3 weeks between cycles.

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network, Princess Margaret Cancer Centre	Toronto	Ontario
Canada	The Prostate Centre	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

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