Prostate CancerPhase 1/2NCT01171898
Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 (Apalutamide) in Castration-Resistant Prostate Cancer (CRPC)
A Phase 1/2 study testing ARN-509 (Phase 1) and ARN-509 (Phase 2) in people with Prostate Cancer, run by Aragon Pharmaceuticals, Inc. at 15 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- ARN-509 (Phase 1) and ARN-509 (Phase 2)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 15 sitesUnited States
- Study dates
- 26 Jul 2010to 22 Jul 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Histologically or cytologically proven prostate cancer with progressive disease based on either PSA or radiographic progression
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- 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
- 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
- Patients must have received a minimum of 6 months of abiraterone treatment prior to disease progression
Who cannot join
- 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.
Show all 28Show fewer
- 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
- History of, or current metastases in the brain or untreated spinal cord compression
- 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, CHEMOTHERAPY-NAIVE, POST-ABIRATERONE
- History of, or current metastases in the brain or untreated spinal cord compression
- Prior treatment with MDV3100
- 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
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Study site
Ann Arbor, Michigan
Study site
Atlanta, Georgia
Study site
Baltimore, Maryland
Study site
Boston, Massachusetts
Study site
Dallas, Texas
Study site
Lancaster, Pennsylvania
Study site
Madison, Wisconsin
Study site
Myrtle Beach, South Carolina
Study site
New York, New York
Study site
Omaha, Nebraska
Study site
Portland, Oregon
Study site
Raleigh, North Carolina
Study site
San Diego, California
Study site
San Francisco, California
Study site
Seattle, Washington
About this study
Official title: An Open-Label, Phase 1/2, Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 in Patients With Progressive Advanced Castration-Resistant Prostate Cancer
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
- Being tested
- ARN-509 (Phase 1), ARN-509 (Phase 2)
- Keywords
- Non-Metastatic, Rising PSA, Castration-Resistant, Treatment-Naive, Post-abiraterone
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: ARN-509 (Phase 2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 12
Secondary outcomes (4)
Phase 1 and 2: Median Time to PSA Progression
Time to PSA progression was measured as the time interval from the date of the first dose to the date of PSA progression as defined by the PCWG2 criteria. PCWG2 criteria: For participants who achieved >=50% decrease from the baseline PSA, assessment of time to disease progression was when the PSA increased 25% and at a minimum of 2 ng/mL above the nadir at 3 or more weeks later. For participants without a PSA decrease, the time for progression was calculated at the time when the PSA progression was >=25% and >=2 ng/mL after 12 weeks.
Measured: Up to approximately 7 years
Phase 2: Median Metastasis-Free Survival (MFS)
MFS was defined as the time from the start of treatment until new metastatic lesions were observed on Computed Tomography/ Magnetic Resonance Imaging (CT/MRI) scans or radionuclide bone scans (according to PCWG2 criteria: appearance of >=2 new lesions, and, for the first reassessment only, a confirmatory scan performed 6 or more weeks later that showed at least 2 or more additional new lesions) or death, whichever occurred first.
Measured: Up to approximately 7 years
Phase 1 and 2: Progression-free Survival (PFS)
PFS was defined as the time from randomization to the radiographic disease progression or death, whichever occurred first. Radiographic progression defined by at least one of the following: a) Soft tissue progression by modified RECIST confirmed on repeat imaging >= 6 weeks later; b) Progression by bone scans: 1) first bone scan with >= 2 new lesions compared to baseline observed <12 weeks from start date and confirmed on a second bone scan >=6 weeks later that showed >=2 additional lesions (a total of >=4 new lesions compared to baseline); or 2) first bone scan with >=2 new lesions compared to baseline observed >=12 weeks from start date and the new lesions verified on the next bone scan >=6 weeks later (a total of >=2 new lesions compared to baseline).
Measured: Up to approximately 7 years
Phase 1 and 2: Objective Response Rate
Objective Response Rate was defined as the percentage of participants with best overall response (OR) of confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.0 (RECIST). Where, CR defined as disappearance of all target lesions. Any pathological lymph nodes must had reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions. Confirmed responses were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response.
Measured: Up to approximately 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2010 (estimated)
- Study start26 Jul 2010
- Primary completion20 Aug 2012
- Study completion22 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aragon Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Aragon Pharmaceuticals, Inc Clinical Trial, Study director, Aragon Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01171898
- Sponsor's protocol ID
- CR103304
- Other IDs
- ARN-509-001
- Status last verified
- Jun 2026
- First submitted
- 27 Jul 2010
- Last updated
- 5 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28633425Smith 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.
PubMed 27160947
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase 1/2, Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 in Patients With Progressive Advanced Castration-Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT01171898
- Acronym / sponsor ID
- CR103304
- Conditions
- Prostate Cancer
- Keywords
- Non-Metastatic, Rising PSA, Castration-Resistant, Treatment-Naive, Post-abiraterone
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Aragon Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 26 Jul 2010 (actual)
- Primary completion
- 20 Aug 2012 (actual)
- Study completion
- 22 Jul 2025 (actual)
- First posted
- 29 Jul 2010 (estimated)
- Results
- Posted 27 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Cohort (Phase 1) | Experimental | Drug: 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. 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. |
| Non-metastatic CRPC (Phase 2) | Experimental | Drug: ARN-509 (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. |
| Treatment-naive metastatic CRPC (Phase 2) | Experimental | Drug: ARN-509 (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. |
| Post-abiraterone metastatic CRPC (Phase 2) | Experimental | Drug: ARN-509 (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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Dose Escalation Cohort (Phase 1) |
| 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. | Drug | Non-metastatic CRPC (Phase 2), Post-abiraterone metastatic CRPC (Phase 2), Treatment-naive metastatic CRPC (Phase 2) |
Primary outcome
Phase 1 and 2: Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) at Week 12
Time frame: 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.
4 secondary outcomes
Phase 1 and 2: Median Time to PSA Progression
Time frame: Up to approximately 7 years
Phase 2: Median Metastasis-Free Survival (MFS)
Time frame: Up to approximately 7 years
Phase 1 and 2: Progression-free Survival (PFS)
Time frame: Up to approximately 7 years
Phase 1 and 2: Objective Response Rate
Time frame: Up to approximately 7 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28633425Rathkopf 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.
- Derived from this study: PubMed 27160947Smith 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aragon Pharmaceuticals, Inc Clinical Trial study director
Aragon Pharmaceuticals, Inc.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ARN-509 (Phase 1) and ARN-509 (Phase 2) in people with Prostate Cancer, run by Aragon Pharmaceuticals, Inc. at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1 and 2: Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) at Week 12 (time frame: Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01171898, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2026.