Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of Ascending Doses of ARN 509 in Combination With Abiraterone Acetate

NCT01792687 | Completed Phase 1

• 3 other identifiers: CR10330612-338ARN-509-004
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase Ib, open label study of ARN-509 administered in combination with abiraterone acetate and prednisone in patients with metastatic castration-resistant prostate cancer.

Conditions

Prostate Cancer

Keywords

Metastatic castrate resistant prostate cancer (CRPC)

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) / Recommended Phase 2 dosage (RP2D)

  To determine the Maximum Tolerated Dosage (MTD)/ Recommended Phase 2 dosage (RP2D) of ARN-509 when administered in combination with abiraterone acetate.

  12 months

Secondary Outcomes (4)

• Pharmacokinetics

  12 months

• Anti-tumor activity

  12 months

• PSA Response

  12 months

• Treatment Response/Resistance

  12 months

Study Arms (1)

Treatment

EXPERIMENTAL

ARN-509 when combined with the approved dose of abiraterone acetate (1,000 mg daily) plus prednisone (5 mg daily).

Drug: ARN-509; Drug: Abiraterone acetate; Drug: Prednisone

Interventions

ARN-509 DRUG

Dose-escalation: 120 milligram (mg), 180 mg, 240 mg, oral, daily

Treatment

Abiraterone acetate DRUG

1,000 mg, oral, daily

Treatment

Prednisone DRUG

5 mg, oral, daily

Treatment

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed prostate cancer.
• Radiographic evidence of metastatic disease, detectable by bone scan, CT scan, or MRI. At least one site of metastatic disease must be amenable to needle biopsy.
• Castrate levels of testosterone (testosterone \< 50 ng/dL) on androgen deprivation therapy (ADT). Patients who have not undergone orchiectomy will continue gonadotropin releasing hormone (GnRH) agonist or antagonist therapy.
• Age \> 18 years
• ECOG performance status \< 2
• Evidence of disease progression on ADT. Patients must have two serial rises in PSA from nadir, with at least 1 week between PSA measurements, with a minimum PSA of 2 ng/mL, OR patients must have radiographic evidence of progression. Nadir is defined as the lowest PSA value after beginning the most recent therapy for metastatic CRPC.

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Participants may not be receiving any other study agents.
• Participants with known brain metastases
• Any history of seizure or a condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy).
• Concurrent therapy with medications known to have seizure potential (those must have been discontinued or substituted for at least 28 days prior to starting the trial)
• Concurrent treatment with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice) or inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort)
• History of pituitary dysfunction
• History of adrenal dysfunction
• Requirement for steroid use greater than 10 mg of prednisone daily
• History of gastrointestinal disorder or prior extensive gastrointestinal surgery that may interfere with sufficient absorption of the study compounds.
• Prior history of CYP17 inhibitors (e.g., abiraterone acetate, TAK-700) and second-generation anti-androgen (e.g., MDV3100)

Sponsors & Collaborators

• Aragon Pharmaceuticals, Inc.: lead

Study Sites (1)

Unknown Facility

Boston, Massachusetts, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; Abiraterone Acetate; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Aragon Pharmaceuticals, Inc Clinical Trial

  Aragon Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 12, 2013
• First Posted: February 15, 2013
• Study Start: February 5, 2013
• Primary Completion: May 10, 2014
• Study Completion: February 13, 2024
• Last Updated: March 4, 2025

Record last verified: 2025-03

Locations

US (1)