Clinical trial NCT01017939: A Drug-Drug Interaction Study of Abiraterone Acetate Plus Prednisone With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer
Official title: An Abiraterone Acetate Plus Prednisone Drug-Drug Interaction Study With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Neoplasms
Keywords: Prostate neoplasms
Metastatic castration resistant prostate cancer
Metastatic castration refractory prostate cancer
Prostate cancer
Abiraterone acetate
CB7630
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2009-11-23
Enrollment: 34
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 evaluate the effects of multiple doses of abiraterone acetate plus prednisone on the pharmacokinetics (study of what the body does to a drug) of single doses of dextromethorphan hydrobromide and theophylline in patients with castration resistant prostate cancer.

Detailed description: This is an open-label (identity of assigned study drug will be known) study of abiraterone acetate plus prednisone in male patients with metastatic castration-resistant prostate cancer. This study will consist of screening, treatment, and follow-up periods, and will have 2 study groups. Patients in Group A and B will receive daily abiraterone acetate (1000 mg) plus prednisone (5 mg) twice daily beginning on Cycle 1 Day 1 until disease progression. Patients in Group A will take dextromethorphan hydrobromide 30 mg administered orally once daily on Day -8 and Day 8 of Cycle 1. Patients in Group B will take theophylline 100 mg administered orally once daily on Day -8 and Day 8 of Cycle 1. Serial pharmacokinetic samples will be collected and safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology
* Documented metastatic disease
* Documented prostate specific antigen (PSA) progression according to Prostate Cancer Working Group 2 criteria, with PSA value \>=2 ng/mL despite medical or surgical castration, or prostate cancer progression documented by radiographic progression according to Response Evaluation Criteria In Solid Tumors criteria
* Surgically or medically castrated with testosterone levels of \<50 ng/dL
* Eastern Cooperative Oncology Group (ECOG) Performance Status of \<=2
* Group A only: genomic testing at screening indicating CYP2D6 extensive metabolizer status
* Protocol-defined laboratory values

Exclusion Criteria:

* Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection
* Group A only: genomic testing at screening indicating CYP2D6 non-extensive metabolizer status, or prior treatment with dextromethorphan-containing medication or any medication that is a strong inhibitor or inducer of CYP2D6 within 5 half-lives of that drug or 7 days, whichever is longer, prior to Cycle 1 Day -8
* Group B only: prior treatment with theophylline or any medication that is a strong inhibitor or inducer of CYP1A2 within 5 half-lives of that drug or 7 days, whichever is longer, prior to Cycle 1 Day -8
* Abnormal liver function
* Uncontrolled hypertension (repeated systolic blood pressure \>=160 mmHg, or diastolic blood pressure \>=95 mmHg)
* Active or symptomatic viral hepatitis or chronic liver disease
* Known brain metastasis
* History of pituitary or adrenal dysfunction
* Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association Class III or IV heart disease or cardiac ejection fraction measurement of \<50% at baseline
* History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
* Surgery or local prostatic intervention within 28 days of the first dose, and any clinically relevant sequelae from the surgery must have resolved prior to Cycle 1 Day 1
* Radiotherapy or immunotherapy within 28 days, or single fraction of palliative radiotherapy within 14 days of administration of Cycle 1 Day 1
* Any acute toxicities due to prior therapy that have not resolved
* Current enrollment in an investigational drug or device study or participation in such a study within 28 days of Cycle 1 Day 1
* Previous abiraterone acetate or other investigational CYP17 inhibitor (eg, TAK-700)

Primary outcomes:
measure: Ratio of the mean area under the concentration curve (AUC) of dextromethorphan, dextrorphan, and parent/metabolite, with and without co-administration of abiraterone acetate and prednisone
timeFrame: Cycle 1 Day -8 and Day 8
measure: Ratio of the mean maximum plasma concentration (Cmax) of dextromethorphan, dextrorphan, and parent/metabolite, with and without co-administration of abiraterone acetate and prednisone
timeFrame: Cycle 1 Day -8 and Day 8
measure: Ratio of the mean area under the concentration curve (AUC) of theophylline with and without co-administration of abiraterone acetate and prednisone
timeFrame: Cycle 1 Day -8 and Day 8
measure: Ratio of the mean maximum plasma concentration (Cmax) of theophylline with and without co-administration of abiraterone acetate and prednisone
timeFrame: Cycle 1 Day -8 and Day 8
Secondary outcomes:
measure: Number of participants reporting adverse events
timeFrame: Up to 30 days after the last dose of study drug
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Beverly Hills
country: United States
state: California
city: San Antonio
country: United States
facility: START - South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: San Antonio
country: United States
state: Texas
city: Vancouver
country: Canada
facility: BC Cancer Agency
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: