Effect of Low-dose 500 mg Abiraterone Acetate in Treatment of Metastatic Prostate Cancer Patients

NCT06193993 | Active Not Recruiting Phase 1

• 1 other identifier: NUH-DSRB-2020/00258
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This will be an open label, Phase I study to assess the efficacy of a reduced 500 mg dose of abiraterone acetate in patients with metastatic prostate cancer. Eligible metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC) patients newly initiated on abiraterone acetate treatment will be recruited to receive a reduced 500 mg dose of abiraterone acetate plus prednisolone. The study treatment duration will span 12 weeks, after which patients being administered the reduced dose will be reverted to the standard 1000 mg dosing. Follow-up for mCRPC and mHSPC patients will last for 18 and 36 months respectively. The main question the study aims to answer is whether dose reduction of abiraterone acetate to 500 mg would achieve antitumor activity in mCRPC and mHPSC patients comparable to standard of care.

Conditions

Prostate Cancer; Metastatic Cancer; Hormone Sensitive Prostate Cancer; Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with greater than or equal to 50 percent decrease in Prostate Specific Antigen (PSA) levels

  Baseline up to Week 12

Secondary Outcomes (11)

• Maximum Plasma Concentration (Cmax) of 500 mg dose of Abiraterone Acetate

  Pre-dose and 0.5, 1, 2, 3, 4 and 6 hours post-dose on Visit 1 (Week 2 from start of treatment)

• Time to Reach the Maximum Plasma Concentration (Tmax) of 500 mg dose of Abiraterone Acetate

  Pre-dose and 0.5, 1, 2, 3, 4 and 6 hours post-dose on Visit 1 (Week 2 from start of treatment)

• Area under the plasma concentration time curve from time 0 to 6 hours (AUC0-6h) of 500 mg dose of Abiraterone Acetate

  Pre-dose and 0.5, 1, 2, 3, 4 and 6 hours post-dose on Visit 1 (Week 2 from start of treatment)

• Area under the plasma concentration time curve from time 0 to infinity time (AUC0-inf) of 500 mg dose of Abiraterone Acetate

  Pre-dose and 0.5, 1, 2, 3, 4 and 6 hours post-dose on Visit 1 (Week 2 from start of treatment). On Visits 2 (Week 4), 3 (Week 8) and 4 (Week 12) pre-dose

• Volume of distribution (Vd) of 500 mg dose of Abiraterone Acetate

  Pre-dose and 0.5, 1, 2, 3, 4 and 6 hours post-dose on Visit 1 (Week 2 from start of treatment). On Visits 2 (Week 4), 3 (Week 8) and 4 (Week 12) pre-dose

Study Arms (1)

Abiraterone Acetate

EXPERIMENTAL

500 mg dose of Abiraterone Acetate plus prednisolone

Drug: Abiraterone Acetate

Interventions

Abiraterone Acetate DRUG

Upon successful registration, patients would be initiated on 500 mg once daily (two 250 mg tablets), plus prednisolone 5 mg twice daily orally for mCRPC and 5mg once daily orally for mHSPC.

Abiraterone Acetate

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma prostate
• Age \>21 years
• Diagnosis of metastatic castration-resistant prostate cancer (mCRPC) (chemotherapy naïve and chemotherapy pre-treated patients) or metastatic hormone-sensitive prostate cancer (mHSPC)
• For mCRPC patients, evidence of castration resistance is defined as disease progression despite a testosterone level \<50ng/dL (or surgical castration)
• Progressive disease was defined as either
• PSA progression according to Prostate Cancer Working Group (PCWG2) criteria15: PSA evidence for progressive prostate cancer consists of a minimum PSA level of at least 2 ng/ml, which has subsequently risen on at least 2 successive occasions, at least 1 week apart
• Radiographic progression according to RECIST 1.1 guidelines or
• or more new lesions on bone scan
• Newly initiated on abiraterone acetate therapy
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2.
• Adequate hematologic, hepatic, and renal function would include:
• hemoglobin ≥9.0 g/dL independent of transfusions
• neutrophils ≥1.5 x 109/L
• platelets ≥100 x 109/L
• total bilirubin ≤1.5× upper limit of normal (ULN) \[except for subjects with documented Gilbert's disease in which case total bilirubin not to exceed 10× ULN\]

You may not qualify if:

• Patients with prior use of enzalutamide or other potent androgen pathway targeted therapies
• Concurrent therapy with strong inhibitors or inducers of CYP3A4 due to concerning possible drug-drug interactions with abiraterone.
• Concurrent therapy with strong inhibitors or inducers of OATP transporters (e.g., rifampicin, cyclosporine) due to concerning possible effects on CP-I and CP-III.
• New York Heart Association (NYHA) class II, NYHA class III, or IV congestive heart failure (any symptomatic heart failure)
• Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic BP ≥95 mmHg). Subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
• Patients who do not voluntarily consent to participate in the study

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• National University of Singapore: collaborator

Study Sites (1)

National University Hospital

Singapore, Singapore

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

Abiraterone Acetate

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Edmund Chiong, MBBS, PhD

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2023
• First Posted: January 8, 2024
• Study Start: November 30, 2021
• Primary Completion: September 5, 2023
• Study Completion (Estimated): September 1, 2026
• Last Updated: January 8, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)