Clinical trial NCT01424930: A Study to Determine the Short-Term Safety of Continuous Dosing of Abiraterone Acetate and Prednisone in Modified Fasting and Fed States to Patients With Metastatic Castration-Resistant Prostate Cancer
Official title: An Open-Label Study to Determine the Short-Term Safety of Continuous Dosing of Abiraterone Acetate and Prednisone in Modified Fasting and Fed States to Subjects With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Neoplasms
Prostate Cancer
Keywords: Metastatic castration-resistant prostate cancer
CRPC
Abiraterone Acetate
Prednisone
Food Safety
Lead sponsor: Janssen-Ortho Inc., Canada
Sponsor class: INDUSTRY
First posted: 2011-08-29
Enrollment: 25
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to establish the safety profile of oral (by mouth) abiraterone acetate and oral prednisone following short-term administration after standardized low-fat or high-fat meals to patients with metastatic (spreading) castration-resistant prostate cancer (mCRPC).

Detailed description: This is a multicenter, open-label study of 24 (up to a total of 28) men to assess the short-term safety of oral abiraterone acetate 1 g and oral prednisone 5 mg twice daily administered in the modified fasted state and after meals of various fat contents. All patients will take daily abiraterone acetate for the first 7 days in the modified fasted state (no food for 2 hours before and 1 hour after the dose). In Cohort 1, up to 6 evaluable patients will take abiraterone acetate daily for 7 days after a standardized low-fat meal from Cycle 1 Day 8 to Cycle 1 Day 14; or, in Cohort 2, up to 6 evaluable patients will take abiraterone acetate daily for 7 days after a standardized high-fat meal from Cycle 1 Day 8 to Cycle 1 Day 14. All patients will then continue to take abiraterone acetate daily in the modified fasted state starting on Cycle 1 Day 15 until disease progression. Toxicity related to dosing after the low-fat or high-fat meals is defined as Grade 3 or higher AEs of special interest; or Grade 3 or higher serious adverse events (SAEs) that occur during the food safety evaluation period. Cohort 2 may be expanded to a total of 18 evaluable patients if deemed to be safe. Decisions regarding the escalation of cohort or expansion of cohorts will be made by a study evaluation team. Pharmacokinetic evaluation for each cohort will be performed on Cycle 1 Days 7 and 14 at predose and multiple timepoints postdose over 24 hours; Cycle 1 Days 8 and 11 at 2 hours following abiraterone acetate dose administration. Abiraterone acetate, 1 g (four 250-mg tablets) orally (taken by mouth) once daily. Patients may take abiraterone acetate until progression of clinical disease. Prednisone, 5 mg, orally, twice a day.

Eligibility criteria: Inclusion Criteria:

* Adenocarcinoma of the prostate
* Metastatic disease documented by bone, computed tomography (CT) or magnetic resonance imaging (MRI) scan
* Surgical or medical castration with testosterone less than 50 ng/dL (\< 2.0 nM)
* Prostate-specific antigen (PSA) or radiographic progression documented by assessments specified in study protocol
* Platelets \>100,000/µl
* Hemoglobin \>=9.0 g/dL
* Liver function tests (LFTs): Serum bilirubin \< 1.5 x ULN; AST or ALT \< 2.5 x ULN; Eastern Cooperative Oncology Group (ECOG) status score of \<=2

Exclusion Criteria:

* Small cell carcinoma of the prostate
* Known brain metastasis, chronic liver disease with elevated LFTs
* Prior cytotoxic chemotherapy for metastatic prostate cancer
* Treatment of prostate cancer within 30 days of Day 1 Cycle 1 with surgery, radiation, chemotherapy or immunotherapy
* Use of investigational drug within 30 days of Day 1 Cycle 1 or current enrollment in an investigational drug or device study
* Recent history of ischemic heart disease, Electrocardiogram (ECG) abnormalities or atrial fibrillation
* Active infection or other medical condition that would make prednisone (corticosteroid) use contraindicated
* Chronic medical condition requiring a higher dose of corticosteroid than prednisone 5 mg twice daily

Primary outcomes:
measure: Number of Participants With Grade 3 or Higher Adverse Events (AEs) of Special Interest or Grade 3 or Higher Serious AEs Due to Study Medication
timeFrame: Postdose on Cycle 1 Day 8 to predose on Cycle 2 Day 1
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Abiraterone
timeFrame: Day 7 and Day 14
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Abiraterone
timeFrame: Day 7 and Day 14
measure: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
timeFrame: Day 7 and Day 14
Other outcomes:
Locations:
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
Study officials:
affiliation: Janssen-Ortho Inc., Canada
name: Janssen-Ortho, Canada Clinical Trial
role: STUDY_DIRECTOR
References: