A Study of JNJ-56021927 (ARN-509) and Abiraterone Acetate in Participants With Metastatic Castration-Resistant Prostate Cancer

• ClinicalTrials.gov Identifier: NCT02123758
• Recruitment Status: Active, not recruiting
• First Posted: April 28, 2014
• Last Update Posted: September 28, 2022
• Sponsor: Aragon Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Aragon Pharmaceuticals, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Prostatic Neoplasms; Metastatic Castration-Resistant Prostate Cancer	Drug: Abiraterone Acetate; Drug: Prednisone; Drug: JNJ-56021927	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: July 9, 2014
• Actual Primary Completion Date: June 27, 2016
• Estimated Study Completion Date: October 15, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; Participants will receive abiraterone acetate (AA) along with prednisone on Day 1, Treatment Cycle 1 up to Day 7, Treatment Cycle 1; followed by combined intake of abiraterone acetate + prednisone (AAP) + JNJ-56021927 from Day 8, Treatment Cycle 1 up to the end of treatment (EoT) visit (ie, up to approximately 18 months). On Day 8, Treatment Cycle 2 participants will receive JNJ-56021927, 1 hour after intake of AA and prednisone. Breakfast will be offered approximately 30 minutes after intake of JNJ-56021927. Treatment cycles will be of 28 days.	Drug: Abiraterone Acetate; Administered orally (by mouth) once daily in morning at a dose of 1000 mg for up to the end of treatment (EoT) visit (ie, for up to approximately 18 months).; Other Name: ZYTIGA; Drug: Prednisone; Administered orally twice a day at a dose of 5mg for up to the end of treatment (EoT) visit (ie, for up to approximately 18 months).; Drug: JNJ-56021927; Administered orally once daily in morning at a dose of 240 mg starting on Day 8, Treatment Cycle 1 for up to the end of treatment (EoT) visit (ie, for up to approximately 18 months).
Experimental: Cohort 2; Participants will receive abiraterone acetate (AA) along with prednisone on Day 1, Treatment Cycle 1 up to Day 7, Treatment Cycle 1; followed by combined intake of AAP + JNJ-56021927 from Day 8, Treatment Cycle 1 up to the end of treatment (EoT) visit (ie, up to approximately 18 months). On Days 7 and 36, participants will receive AA and prednisone together. On Day 8, Treatment Cycle 2 participants will receive JNJ-56021927, 1 hour after intake of AAP. Treatment cycles will be of 28 days.	Drug: Abiraterone Acetate; Administered orally (by mouth) once daily in morning at a dose of 1000 mg for up to the end of treatment (EoT) visit (ie, for up to approximately 18 months).; Other Name: ZYTIGA; Drug: Prednisone; Administered orally twice a day at a dose of 5mg for up to the end of treatment (EoT) visit (ie, for up to approximately 18 months).; Drug: JNJ-56021927; Administered orally once daily in morning at a dose of 240 mg starting on Day 8, Treatment Cycle 1 for up to the end of treatment (EoT) visit (ie, for up to approximately 18 months).

Outcome Measures

Primary Outcome Measures :

1. Area Under the Plasma Concentration-time Curve From Time Zero to Time 24 Hours (AUC [0-24]) of abiraterone [ Time Frame: Day 7 (Treatment Cycle 1) and on Day 36 (Treatment Cycle 2) ]
   The AUC (0-24) is area under the plasma concentration-time curve from time zero to time 24 hours.
2. Maximum plasma concentration (Cmax) of abiraterone, prednisone and its metabolite prednisolone [ Time Frame: Day 7 (Treatment Cycle 1) and on Day 36 (Treatment Cycle 2) ]
   The Cmax is the maximum observed plasma concentration.
3. Area Under the Plasma Concentration-time Curve From Time Zero to Time 12 Hours (AUC [0-12]) of prednisone and its metabolite prednisolone [ Time Frame: Day 7 (Treatment Cycle 1) and on Day 36 (Treatment Cycle 2) ]
   The AUC (0-12) is area under the plasma concentration-time curve from time zero to time 12 hours.

Secondary Outcome Measures :

1. Area Under the Plasma Concentration Curve (AUC [0- 24h]) of JNJ-56021927 and its metabolite JNJ-56142060 [ Time Frame: Day 36 (Treatment Cycle 2), on Day 57 (Treatment Cycle 3) ]
   The AUC (0-24) is area under the plasma concentration-time curve from time zero to time 24 hours.
2. Maximum plasma concentration (Cmax) of JNJ-56021927 and its metabolite JNJ-56142060 [ Time Frame: Day 36 (Treatment Cycle 2), on Day 57 (Treatment Cycle 3) ]
   The Cmax is the maximum observed plasma concentration.
3. Change in prostate specific antigen (PSA) [ Time Frame: Up to the end of the treatment phase (approximately 18 months) ]
   Prostate-specific antigen (PSA) is a protein produced by cells of the prostate gland.
4. Maximal decline in prostate specific antigen (PSA) [ Time Frame: Up to the end of the treatment phase (approximately 18 months) ]
   Prostate-specific antigen (PSA) is a protein produced by cells of the prostate gland.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Los Angeles, California, United States

San Francisco, California, United States

United States, Texas

Houston, Texas, United States

Canada, British Columbia

Vancouver, British Columbia, Canada

Canada, Quebec

Montreal, Quebec, Canada

Netherlands

Rotterdam, Netherlands

United Kingdom

Sutton, United Kingdom

Sponsors and Collaborators

Aragon Pharmaceuticals, Inc.

Investigators

• Study Director: Aragon Pharmaceuticals, Inc. Clinical Trial; Aragon Pharmaceuticals, Inc.

More Information

• Responsible Party: Aragon Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02123758
• Other Study ID Numbers: CR104358; 56021927PCR1010 ( Other Identifier: Aragon Pharmaceuticals, Inc. ); 2014-001426-14 ( EudraCT Number )
• First Posted: April 28, 2014
• Last Update Posted: September 28, 2022
• Last Verified: September 2022

• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aragon Pharmaceuticals, Inc.:

Prostatic Neoplasms; Metastatic Castration-Resistant Prostate Cancer (mCRPC); Prostate cancer; Abiraterone Acetate (ZYTIGA); Prednisone; JNJ-56021927

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Prednisone; Abiraterone Acetate; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors