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

Phase Ib, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of Ascending Doses of ARN-509 in Combination With Abiraterone Acetate in Patients With Metastatic Castrate Resistant Prostate Cancer (CRPC)

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: ARN-509; Drug: Abiraterone acetate; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; ARN-509 when combined with the approved dose of abiraterone acetate (1,000 mg daily) plus prednisone (5 mg daily).	Drug: ARN-509; Dose-escalation: 120 milligram (mg), 180 mg, 240 mg, oral, daily; Drug: Abiraterone acetate; 1,000 mg, oral, daily; Drug: Prednisone; 5 mg, oral, daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	To characterize the pharmacokinetics (PK) of abiraterone at steady-state prior to ARN-509 administration, and both abiraterone and ARN-509 at steady-state following combined dosing of both agents.	12 months
Anti-tumor activity	To perform preliminary assessment of the anti-tumor activity of ARN 509 in combination with abiraterone acetate by evaluation of radiographic tumor response by modified RECIST criteria.	12 months
PSA Response	To assess the magnitude and duration of PSA response in patients receiving ARN 509 plus abiraterone acetate.	12 months
Treatment Response/Resistance	To analyze potential mechanisms of response and resistance to treatment with ARN-509 plus abiraterone acetate in tissue obtained from serial biopsies of CRPC.	12 months

Collaborators and Investigators

• Sponsor: Aragon Pharmaceuticals, Inc.
• Investigators: Study Director: Aragon Pharmaceuticals, Inc Clinical Trial, Aragon Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2013
• Primary Completion (Actual): May 10, 2014
• Study Completion (Actual): February 13, 2024

Study Registration Dates

• First Submitted: February 12, 2013
• First Submitted That Met QC Criteria: February 14, 2013
• First Posted (Estimated): February 15, 2013

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Metastatic castrate resistant prostate cancer (CRPC)
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Prednisone; Abiraterone Acetate
• Other Study ID Numbers: CR103306; 12-338 (Other Identifier: Dana Farber / Harvard Cancer Center); ARN-509-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No