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

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ClinicalTrials.gov Identifier: NCT01171898
Recruitment Status : Active, not recruiting
First Posted : July 29, 2010
Results First Posted : July 27, 2018
Last Update Posted : March 2, 2021
Sponsor:
Information provided by (Responsible Party):
Aragon Pharmaceuticals, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: ARN-509 (Phase 1) Drug: ARN-509 (Phase 2) Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 127 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 26, 2010
Actual Primary Completion Date : August 20, 2012
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Apalutamide

Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 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.
Experimental: 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.
 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.
Experimental: 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.
 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.
Experimental: 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.
 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.


Outcome Measures
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Primary Outcome Measures :
  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 [ 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.


Secondary Outcome Measures :
  1. Phase 1 and 2: Median Time to PSA Progression [ Time Frame: Up to approximately 7 years ]
    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.

  2. Phase 2: Median Metastasis-Free Survival (MFS) [ Time Frame: Up to approximately 7 years ]
    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.

  3. Phase 1 and 2: Progression-free Survival (PFS) [ Time Frame: Up to approximately 7 years ]
    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).

  4. Phase 1 and 2: Objective Response Rate [ Time Frame: Up to approximately 7 years ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

NON-METASTATIC CRPC

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

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

Inclusion Criteria

  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

Exclusion Criteria

  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

Inclusion Criteria

  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. 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
Contacts and Locations
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01171898


Locations
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United States, California
San Diego, California, United States
San Francisco, California, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Michigan
Ann Arbor, Michigan, United States
United States, Nebraska
Omaha, Nebraska, United States
United States, New York
New York, New York, United States
United States, North Carolina
Raleigh, North Carolina, United States
United States, Oregon
Portland, Oregon, United States
United States, Pennsylvania
Lancaster, Pennsylvania, United States
United States, South Carolina
Myrtle Beach, South Carolina, United States
United States, Texas
Dallas, Texas, United States
United States, Washington
Seattle, Washington, United States
United States, Wisconsin
Madison, Wisconsin, United States
Sponsors and Collaborators
Aragon Pharmaceuticals, Inc.
Investigators
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Study Director: Aragon Pharmaceuticals, Inc Clinical Trial Aragon Pharmaceuticals, Inc.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01171898    
Other Study ID Numbers: CR103304
ARN-509-001 ( Other Identifier: Aragon Pharmaceuticals, Inc )
First Posted: July 29, 2010    Key Record Dates
Results First Posted: July 27, 2018
Last Update Posted: March 2, 2021
Last Verified: February 2021
Keywords provided by Aragon Pharmaceuticals, Inc.:
Non-Metastatic
Rising PSA
Castration-Resistant
Treatment-Naive
Post-abiraterone
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
 Neoplasms by Site
Neoplasms
Prostatic Diseases