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

NCT ID: NCT02543255

Last Updated: 2024-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2021-07-20

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Abiraterone acetate with prednisone

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Cabazitaxel with peg-filgrastim

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Abiraterone acetate with prednisone

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Leuprolide

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

Intervention Type: DRUG

Cabazitaxel with peg-filgrastim

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

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Neil E Fleshner, MD, MPH, FRCSC

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Anthony Joshua, BSc (Med), MBBS, PhD, FRACP

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

The Prostate Centre

Vancouver, British Columbia, 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

Countries

Canada

Other Identifiers

15-051

Identifier Type: -

Identifier Source: org_study_id