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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01792687
First received: February 12, 2013
Last updated: October 30, 2014
Last verified: October 2014
  Purpose

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 Intervention Phase
Prostate Cancer
Drug: ARN-509
Drug: Abiraterone acetate
Drug: Prednisone
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Aragon Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) / Recommended Phase 2 dosage (RP2D) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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:
  • Pharmacokinetics [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • Anti-tumor activity [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • PSA Response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To assess the magnitude and duration of PSA response in patients receiving ARN 509 plus abiraterone acetate.

  • Treatment Response/Resistance [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To analyze potential mechanisms of response and resistance to treatment with ARN-509 plus abiraterone acetate in tissue obtained from serial biopsies of CRPC.


Enrollment: 6
Study Start Date: February 2013
Estimated Study Completion Date: December 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: 90 mg, 120 mg, 240 mg, oral, daily
Drug: Abiraterone acetate
1,000 mg, oral, daily
Drug: Prednisone
5 mg, oral, daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01792687

Locations
United States, California
San Francisco, California, United States
United States, Massachusetts
Boston, Massachusetts, United States
Sponsors and Collaborators
Aragon Pharmaceuticals, Inc.
Investigators
Study Director: Aragon Pharmaceuticals, Inc Clinical Trial Aragon Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01792687     History of Changes
Other Study ID Numbers: CR103306, 12-338, ARN-509-004
Study First Received: February 12, 2013
Last Updated: October 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Aragon Pharmaceuticals, Inc.:
Metastatic castrate resistant prostate cancer (CRPC)

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Prednisone
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014