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

NCT ID: NCT01171898

Last Updated: 2025-11-12

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-07-26

Study Completion Date

2025-07-22

Brief Summary

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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.

Detailed Description

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Conditions

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Prostate Cancer

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Post-abiraterone metastatic CRPC (Phase 2)

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.

Group Type EXPERIMENTAL

ARN-509 (Phase 2)

Intervention Type DRUG

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

Dose Escalation Cohort (Phase 1)

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.

Group Type EXPERIMENTAL

ARN-509 (Phase 1)

Intervention Type 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.

Non-metastatic CRPC (Phase 2)

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.

Group Type EXPERIMENTAL

ARN-509 (Phase 2)

Intervention Type DRUG

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

Treatment-naive metastatic CRPC (Phase 2)

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

Group Type EXPERIMENTAL

ARN-509 (Phase 2)

Intervention Type DRUG

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

Interventions

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ARN-509 (Phase 1)

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.

Intervention Type DRUG

ARN-509 (Phase 2)

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. 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
2. Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
3. Castrate levels of serum testosterone of less than or equal to 50 ng/dL
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
5. A life expectancy of at least 3 months


1. Histologically or cytologically proven prostate cancer with progressive disease based on either PSA or radiographic progression
2. Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
3. Castrate levels of serum testosterone of less than or equal to 50 ng/dL
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
5. A life expectancy of at least 3 months


1. Histologically or cytologically proven prostate cancer with progressive disease based on either PSA or radiographic progression
2. Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
3. Castrate levels of serum testosterone of less than or equal to 50 ng/dL
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
5. A life expectancy of at least 3 months
6. Patients must have received a minimum of 6 months of abiraterone treatment prior to disease progression

Exclusion Criteria

1. Distant metastases, including CNS and vertebral or meningeal involvement
2. Prior treatment with MDV3100
3. Prior treatment with abiraterone
4. Prior treatment with ketoconazole
5. Concurrent treatment with medications known to have seizure potential
6. 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.
7. QTc \> 450 msec
8. History of seizure or condition that may predispose to seizure
9. Evidence of severe or uncontrolled systemic disease or HIV infection

METASTATIC CRPC, TREATMENT-NAIVE


1. History of, or current metastases in the brain or untreated spinal cord compression
2. Prior treatment with MDV3100
3. Prior treatment with abiraterone
4. Prior treatment with ketoconazole
5. Concurrent treatment with medications known to have seizure potential
6. 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.
7. QTc \> 450 msec
8. History of seizure or condition that may predispose to seizure
9. Evidence of severe or uncontrolled systemic disease or HIV infection

METASTATIC CRPC, CHEMOTHERAPY-NAIVE, POST-ABIRATERONE


1. History of, or current metastases in the brain or untreated spinal cord compression
2. Prior treatment with MDV3100
3. Prior treatment with ketoconazole
4. Concurrent treatment with medications known to have seizure potential
5. 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.
6. QTc \> 450 msec
7. History of seizure or condition that may predispose to seizure
8. Evidence of severe or uncontrolled systemic disease or HIV infection
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Aragon Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aragon Pharmaceuticals, Inc Clinical Trial

Role: STUDY_DIRECTOR

Aragon Pharmaceuticals, Inc.

Locations

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San Diego, California, United States

Site Status

San Francisco, California, United States

Site Status

Atlanta, Georgia, United States

Site Status

Baltimore, Maryland, United States

Site Status

Boston, Massachusetts, United States

Site Status

Ann Arbor, Michigan, United States

Site Status

Omaha, Nebraska, United States

Site Status

New York, New York, United States

Site Status

Raleigh, North Carolina, United States

Site Status

Portland, Oregon, United States

Site Status

Lancaster, Pennsylvania, United States

Site Status

Myrtle Beach, South Carolina, United States

Site Status

Dallas, Texas, United States

Site Status

Seattle, Washington, United States

Site Status

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 28633425 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27160947 (View on PubMed)

Other Identifiers

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ARN-509-001

Identifier Type: OTHER

Identifier Source: secondary_id

CR103304

Identifier Type: -

Identifier Source: org_study_id