Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 (Apalutamide) in Castration-Resistant Prostate Cancer (CRPC)

NCT01171898 | Completed Phase 1 Results

• 2 other identifiers: CR103304ARN-509-001
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 15

Brief Summary

The purpose of this study is to assess the safety and activity of ARN-509 in men with advanced castration resistant prostate cancer. Patients will first be enrolled into Phase 1 of the study to identify a tolerable dose for the Phase 2 portion of the study. In the Phase 2, 3 different cohorts of patients will be enrolled to evaluate the safety and activity of ARN-509.

Conditions

Prostate Cancer

Keywords

Non-Metastatic; Rising PSA; Castration-Resistant; Treatment-Naive; Post-abiraterone

Outcome Measures

Primary Outcomes (1)

• Phase 1 and 2: Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) at Week 12

  Percentage of participants with \>=50% decrease in PSA compared to baseline were assessed at Week 12. PSA progression was defined by the protocol-specific Prostate Cancer Working Group 2 (PCWG2) criteria: PSA increase greater than or equal to \[\>=\] 25 percent \[%\] and \>=2 nanogram per milliliter \[ng/mL\] above the nadir confirmed \>=3 weeks later; or \>=25% and \>=2 ng/mL above baseline PSA after 12 weeks.

  Week 12

Secondary Outcomes (4)

• Phase 1 and 2: Median Time to PSA Progression

  Up to approximately 7 years

• Phase 2: Median Metastasis-Free Survival (MFS)

  Up to approximately 7 years

• Phase 1 and 2: Progression-free Survival (PFS)

  Up to approximately 7 years

• Phase 1 and 2: Objective Response Rate

  Up to approximately 7 years

Study Arms (4)

Dose Escalation Cohort (Phase 1)

EXPERIMENTAL

ARN-509 will be administered at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily. Once Recommended Phase 2 Dose (RP2D) has been selected, Phase 1 participants being treated at the lower dose levels will be allowed to escalate to the RP2D level at the discretion of the primary investigator.

Drug: ARN-509 (Phase 1)

Non-metastatic CRPC (Phase 2)

EXPERIMENTAL

Participants with non-metastatic, treatment-naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) will be enrolled. ARN-509 will be administered at Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D), determined in Phase 1.

Drug: ARN-509 (Phase 2)

Treatment-naive metastatic CRPC (Phase 2)

EXPERIMENTAL

Participants with treatment-naive metastatic CRPC will be enrolled. ARN-509 will be administered at MTD and/or RP2D, determined in Phase 1.

Drug: ARN-509 (Phase 2)

Post-abiraterone metastatic CRPC (Phase 2)

EXPERIMENTAL

Participants with metastatic CRPC that are chemotherapy-naive, but have been previously treated with abiraterone will be enrolled. ARN-509 will be administered at MTD and/or RP2D, determined in Phase 1.

Drug: ARN-509 (Phase 2)

Interventions

ARN-509 (Phase 2) DRUG

ARN-509 will be administered at Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D), determined in Phase 1.

Non-metastatic CRPC (Phase 2); Post-abiraterone metastatic CRPC (Phase 2); Treatment-naive metastatic CRPC (Phase 2)

ARN-509 (Phase 1) DRUG

ARN-509 will be administered at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily.

Dose Escalation Cohort (Phase 1)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically proven prostate cancer with high risk for development of metastases, defined as either a PSA value \>=8 ng/mL within the last 3 months or PSA Doubling Time \<=10 months
• Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
• Castrate levels of serum testosterone of less than or equal to 50 ng/dL
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• A life expectancy of at least 3 months

You may not qualify if:

• Distant metastases, including CNS and vertebral or meningeal involvement
• Prior treatment with MDV3100
• Prior treatment with abiraterone
• Prior treatment with ketoconazole
• Concurrent treatment with medications known to have seizure potential
• Concurrent treatment with corticosteroids. If they are already on steroids, patients will be allowed to enroll on the study but will need to taper off as soon as possible.
• QTc \> 450 msec
• History of seizure or condition that may predispose to seizure
• Evidence of severe or uncontrolled systemic disease or HIV infection
• METASTATIC CRPC, TREATMENT-NAIVE
• Histologically or cytologically proven prostate cancer with progressive disease based on either PSA or radiographic progression
• Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
• Castrate levels of serum testosterone of less than or equal to 50 ng/dL
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• A life expectancy of at least 3 months

Sponsors & Collaborators

• Aragon Pharmaceuticals, Inc.: lead

Study Sites (15)

Unknown Facility

San Diego, California, United States

Location

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San Francisco, California, United States

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Atlanta, Georgia, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Omaha, Nebraska, United States

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New York, New York, United States

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Raleigh, North Carolina, United States

Location

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Portland, Oregon, United States

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Lancaster, Pennsylvania, United States

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Myrtle Beach, South Carolina, United States

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Dallas, Texas, United States

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Seattle, Washington, United States

Location

Unknown Facility

Madison, Wisconsin, United States

Location

Related Publications (2)

• Rathkopf DE, Smith MR, Ryan CJ, Berry WR, Shore ND, Liu G, Higano CS, Alumkal JJ, Hauke R, Tutrone RF, Saleh M, Chow Maneval E, Thomas S, Ricci DS, Yu MK, de Boer CJ, Trinh A, Kheoh T, Bandekar R, Scher HI, Antonarakis ES. Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide. Ann Oncol. 2017 Sep 1;28(9):2264-2271. doi: 10.1093/annonc/mdx283.

  PMID: 28633425 DERIVED

• Smith MR, Antonarakis ES, Ryan CJ, Berry WR, Shore ND, Liu G, Alumkal JJ, Higano CS, Chow Maneval E, Bandekar R, de Boer CJ, Yu MK, Rathkopf DE. Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a Potent Androgen Receptor Antagonist, in the High-risk Nonmetastatic Castration-resistant Prostate Cancer Cohort. Eur Urol. 2016 Dec;70(6):963-970. doi: 10.1016/j.eururo.2016.04.023. Epub 2016 May 6.

  PMID: 27160947 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic

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)

Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Limitations and Caveats

These results are up to clinical cutoff (CCO) date 31 March 2017.

Results Point of Contact

• Title: Senior Medical Director, WC Clinical Oncology Department
• Organization: Aragon Pharmaceuticals, Inc.

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Aragon Pharmaceuticals, Inc Clinical Trial

  Aragon Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2010
• First Posted: July 29, 2010
• Study Start: July 26, 2010
• Primary Completion: August 20, 2012
• Study Completion: July 22, 2025
• Last Updated: May 11, 2026
• Results First Posted: July 27, 2018

Record last verified: 2026-05

Locations

US (15)