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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01792687
Recruitment Status : Active, not recruiting
First Posted : February 15, 2013
Last Update Posted : February 12, 2021
Information provided by (Responsible Party):
Aragon Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: ARN-509 Drug: Abiraterone acetate Drug: Prednisone Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : February 5, 2013
Actual Primary Completion Date : May 10, 2014
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) / Recommended Phase 2 dosage (RP2D) [ Time Frame: 12 months ]
    To determine the Maximum Tolerated Dosage (MTD)/ Recommended Phase 2 dosage (RP2D) of ARN-509 when administered in combination with abiraterone acetate.

Secondary Outcome Measures :
  1. Pharmacokinetics [ Time Frame: 12 months ]
    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.

  2. Anti-tumor activity [ Time Frame: 12 months ]
    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.

  3. PSA Response [ Time Frame: 12 months ]
    To assess the magnitude and duration of PSA response in patients receiving ARN 509 plus abiraterone acetate.

  4. Treatment Response/Resistance [ Time Frame: 12 months ]
    To analyze potential mechanisms of response and resistance to treatment with ARN-509 plus abiraterone acetate in tissue obtained from serial biopsies of CRPC.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01792687

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United States, Massachusetts
Boston, Massachusetts, United States
Sponsors and Collaborators
Aragon Pharmaceuticals, Inc.
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Study Director: Aragon Pharmaceuticals, Inc Clinical Trial Aragon Pharmaceuticals, Inc.
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Responsible Party: Aragon Pharmaceuticals, Inc. Identifier: NCT01792687    
Other Study ID Numbers: CR103306
12-338 ( Other Identifier: Dana Farber / Harvard Cancer Center )
First Posted: February 15, 2013    Key Record Dates
Last Update Posted: February 12, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Aragon Pharmaceuticals, Inc.:
Metastatic castrate resistant prostate cancer (CRPC)
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases
Abiraterone Acetate
Anti-Inflammatory Agents
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