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

NCT02543255 | Completed Phase 2 DMC

• 1 other identifier: 15-051
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 5

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

Keywords

High risk

Outcome Measures

Primary Outcomes (1)

• Pathological complete response

  24 weeks from start of treatment.

Secondary Outcomes (15)

• 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

Study Arms (2)

Abiraterone acetate + prednisone + leuprolide + cabazitaxel

EXPERIMENTAL

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; Drug: Leuprolide; Drug: Cabazitaxel with peg-filgrastim

Abiraterone acetate + prednisone + leuprolide

ACTIVE COMPARATOR

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; Drug: Leuprolide

Interventions

Abiraterone acetate with prednisone 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.

Abiraterone acetate + prednisone + leuprolide; Abiraterone acetate + prednisone + leuprolide + cabazitaxel

Leuprolide DRUG

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

Abiraterone acetate + prednisone + leuprolide; Abiraterone acetate + prednisone + leuprolide + cabazitaxel

Cabazitaxel with peg-filgrastim DRUG

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

Abiraterone acetate + prednisone + leuprolide + cabazitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (5)

The Prostate Centre

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

University Health Network, Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; Prednisone; Leuprolide; cabazitaxel; pegfilgrastim

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Neil E Fleshner, MD, MPH, FRCSC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

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

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2015
• First Posted: September 7, 2015
• Study Start: September 1, 2016
• Primary Completion: May 27, 2021
• Study Completion: July 20, 2021
• Last Updated: January 31, 2024

Record last verified: 2024-01

Locations

CA (5)