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

University Health Network, Toronto

Status and phase: Completed; Phase 2

Conditions: Prostate Cancer

Treatments: Drug: Cabazitaxel with peg-filgrastim; Drug: Leuprolide; Drug: Abiraterone acetate with prednisone

Study type: Interventional

Funder types: Other

Identifiers

NCT02543255

15-051

Details and patient eligibility

About

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.

Enrollment: 76 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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76 participants in 2 patient groups

Abiraterone acetate + prednisone + leuprolide + cabazitaxel

Experimental group

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.

Treatment:

Drug: Abiraterone acetate with prednisone

Drug: Cabazitaxel with peg-filgrastim

Drug: Leuprolide

Abiraterone acetate + prednisone + leuprolide

Active Comparator group

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.

Treatment:

Drug: Abiraterone acetate with prednisone

Drug: Leuprolide