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

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

Sponsors

Lead sponsor: Aragon Pharmaceuticals, Inc.

Source Aragon Pharmaceuticals, Inc.
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.

Overall Status Active, not recruiting
Start Date July 26, 2010
Completion Date December 31, 2020
Primary Completion Date August 20, 2012
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Phase 1 and 2: Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) at Week 12 Week 12
Secondary Outcome
Measure Time Frame
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
Enrollment 127
Condition
Intervention

Intervention type: Drug

Intervention name: ARN-509 (Phase 1)

Description: 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.

Arm group label: Dose Escalation Cohort (Phase 1)

Intervention type: Drug

Intervention name: ARN-509 (Phase 2)

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

Eligibility

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

Gender: Male

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Aragon Pharmaceuticals, Inc Clinical Trial Study Director Aragon Pharmaceuticals, Inc.
Location
facility
| San Diego, California, United States
| San Francisco, California, United States
| Atlanta, Georgia, United States
| Baltimore, Maryland, United States
| Boston, Massachusetts, United States
| Ann Arbor, Michigan, United States
| Omaha, Nebraska, United States
| New York, New York, United States
| Raleigh, North Carolina, United States
| Portland, Oregon, United States
| Lancaster, Pennsylvania, United States
| Myrtle Beach, South Carolina, United States
| Dallas, Texas, United States
| Seattle, Washington, United States
| Madison, Wisconsin, United States
Location Countries

United States

Verification Date

May 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Arm group label: Dose Escalation Cohort (Phase 1)

Arm group type: Experimental

Description: 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.

Arm group label: Non-metastatic CRPC (Phase 2)

Arm group type: Experimental

Description: 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.

Arm group label: Treatment-naive metastatic CRPC (Phase 2)

Arm group type: Experimental

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

Arm group label: Post-abiraterone metastatic CRPC (Phase 2)

Arm group type: Experimental

Description: 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.

Study Design Info

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov