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

Sponsor
Aragon Pharmaceuticals, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT01792687
Collaborator
(none)
6
Enrollment
1
Location
1
Arm
103.8
Anticipated Duration (Months)
0.1
Patients Per Site Per Month

Study Details

Study Description

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 DiseaseIntervention/TreatmentPhase
Phase 1

Study Design

Study Type:
Interventional
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 :
Feb 5, 2013
Actual Primary Completion Date :
May 10, 2014
Anticipated Study Completion Date :
Sep 30, 2021

Arms and Interventions

ArmIntervention/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

Outcome Measures

Primary Outcome Measures

  1. Maximum Tolerated Dose (MTD) / Recommended Phase 2 dosage (RP2D) [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 [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 [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 [12 months]

    To assess the magnitude and duration of PSA response in patients receiving ARN 509 plus abiraterone acetate.

  4. Treatment Response/Resistance [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
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)

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1BostonMassachusettsUnited States

Sponsors and Collaborators

  • Aragon Pharmaceuticals, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01792687
Other Study ID Numbers:
  • CR103306
  • 12-338
  • ARN-509-004
First Posted:
Feb 15, 2013
Last Update Posted:
Oct 8, 2021
Last Verified:
Oct 1, 2021
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Aragon Pharmaceuticals, Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 8, 2021