Clinical trial NCT01171898: Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 (Apalutamide) in Castration-Resistant Prostate Cancer (CRPC)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Keywords: Non-Metastatic
Rising PSA
Castration-Resistant
Treatment-Naive
Post-abiraterone
Lead sponsor: Aragon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2010-07-29
Enrollment: 127
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
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
timeFrame: Week 12
Secondary outcomes:
measure: Phase 1 and 2: Median Time to PSA Progression
timeFrame: Up to approximately 7 years
measure: Phase 2: Median Metastasis-Free Survival (MFS)
timeFrame: Up to approximately 7 years
measure: Phase 1 and 2: Progression-free Survival (PFS)
timeFrame: Up to approximately 7 years
measure: Phase 1 and 2: Objective Response Rate
timeFrame: Up to approximately 7 years
Other outcomes:
Locations:
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Atlanta
country: United States
state: Georgia
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Omaha
country: United States
state: Nebraska
city: New York
country: United States
state: New York
city: Raleigh
country: United States
state: North Carolina
city: Portland
country: United States
state: Oregon
city: Lancaster
country: United States
state: Pennsylvania
city: Myrtle Beach
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
Study officials:
affiliation: Aragon Pharmaceuticals, Inc.
name: Aragon Pharmaceuticals, Inc Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.