Clinical trial NCT02123758: A Study of JNJ-56021927 (ARN-509) and Abiraterone Acetate in Participants With Metastatic Castration-Resistant Prostate Cancer
Official title: A Drug-Drug Interaction, Safety and Efficacy Study With JNJ-56021927 (ARN-509) and Abiraterone Acetate in Subjects With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Prostatic Neoplasms
Metastatic Castration-Resistant Prostate Cancer
Keywords: Prostatic Neoplasms
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Prostate cancer
Abiraterone Acetate (ZYTIGA)
Prednisone
JNJ-56021927
Lead sponsor: Aragon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-04-28
Enrollment: 57
Sex: MALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate potential drug-drug interaction (DDI) between JNJ-56021927 and abiraterone acetate and between JNJ-56021927 and prednisone, determine safety of the combination and evaluate in a descriptive manner the efficacy in these participants. It will also, potentially provide dosing recommendations for abiraterone acetate in future studies when combined with JNJ-56021927.

Detailed description: This is a multicenter, open-label (participants will know the identity of study drug received) study in participants with Metastatic Castration-Resistant Prostate Cancer (mCRPC). The study is a single sequence design (ie, all participants will take abiraterone acetate + prednisone \[AAP\] once daily on Days 1-7 of Treatment Cycle 1 and then proceed with combined daily intake of AAP+JNJ-56021927 from Treatment Cycle 1, Day 8 through to the end of treatment \[ie, for up to an expected duration of approximately 18 months\] and will be conducted as two cohorts (group of participant's). The study will consist of a 28-day screening phase to determine eligibility, an open-label treatment phase consisting of 28-day treatment cycles, and a 30-day follow-up phase for collection of adverse events (AE) after last dose of study drug. Participants will have blood samples collected during the study to evaluate pharmacokinetics, safety, and antitumor activity (PSA). Participant safety will also be monitored by the collection of adverse events. Imaging assessments for disease evaluation will be planned at discretion of the Investigator. Once all participants have completed study treatment up to Cycle 3 Day 1, a data cutoff is planned to evaluate the short term safety profile of the combination and to complete the PK analysis up to the cutoff date. All participants will continue on study (ie, to receive treatment) until disease progression, withdrawal of consent, lost to follow-up, or the occurrence of unacceptable toxicity. The end of the study is defined when all participants have completed treatment. Participant's safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (\<=) 2
* Histologically or cytologically confirmed adenocarcinoma of the prostate
* Documentation of metastatic disease
* Prostate cancer progression
* Surgically or medically castrated, with testosterone levels of less than (\<) 50 nanogram per deciliter (ng/dL)
* Adequate bone marrow and organ function

Exclusion Criteria:

* Known brain metastases
* Pathological finding consistent with small cell carcinoma of the prostate
* Administration of an investigational agent within 4 weeks of Treatment Cycle 1, Day 1
* Chemotherapy, or immunotherapy for the treatment of prostate cancer within 4 weeks of Treatment Cycle 1, Day 1
* Therapies that must be discontinued or substituted prior to Treatment Cycle 1, Day 1 include the following: Medications known to lower the seizure threshold; Herbal and non-herbal products that may decrease prostate specific antigen (PSA) levels (that is, saw palmetto, pomegranates or pomegranate juice); Medications known to induce drug metabolizing enzymes such as dexamethasone, rifampicin, carbamazepine, phenytoin, phenobarbital, St. John's wort, etc.; and, potent inhibitors of CYP3A4 or CYP2C8

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Time 24 Hours (AUC [0-24]) of abiraterone
timeFrame: Day 7 (Treatment Cycle 1) and on Day 36 (Treatment Cycle 2)
measure: Maximum plasma concentration (Cmax) of abiraterone, prednisone and its metabolite prednisolone
timeFrame: Day 7 (Treatment Cycle 1) and on Day 36 (Treatment Cycle 2)
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Time 12 Hours (AUC [0-12]) of prednisone and its metabolite prednisolone
timeFrame: Day 7 (Treatment Cycle 1) and on Day 36 (Treatment Cycle 2)
Secondary outcomes:
measure: Area Under the Plasma Concentration Curve (AUC [0- 24h]) of JNJ-56021927 and its metabolite JNJ-56142060
timeFrame: Day 36 (Treatment Cycle 2), on Day 57 (Treatment Cycle 3)
measure: Maximum plasma concentration (Cmax) of JNJ-56021927 and its metabolite JNJ-56142060
timeFrame: Day 36 (Treatment Cycle 2), on Day 57 (Treatment Cycle 3)
measure: Change in prostate specific antigen (PSA)
timeFrame: Up to the end of the treatment phase (approximately 18 months)
measure: Maximal decline in prostate specific antigen (PSA)
timeFrame: Up to the end of the treatment phase (approximately 18 months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Houston
country: United States
state: Texas
city: Vancouver
country: Canada
state: British Columbia
city: Montreal
country: Canada
state: Quebec
city: Rotterdam
country: Netherlands
city: Sutton
country: United Kingdom
Study officials:
affiliation: Aragon Pharmaceuticals, Inc.
name: Aragon Pharmaceuticals, Inc. Clinical Trial
role: STUDY_DIRECTOR
References: