Clinical trial NCT02349139: Safety, Preliminary Efficacy and Pharmacokinetics of ASN001 in Metastatic Castrate Resistant Prostate Cancer
Official title: A Phase 1/2, Open-Label, Uncontrolled, Multiple-Dose Escalation, Cohort Expansion And Extension Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of ASN001 In Subjects With Metastatic Progressive Castrate Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Cancer of the Prostate
Neoplasms, Prostate
Prostate Cancer
Prostatic Cancer
Neoplasms, Prostatic
Prostate Neoplasms, Castration-resistant
Lead sponsor: Asana BioSciences
Sponsor class: INDUSTRY
First posted: 2015-01-28
Enrollment: 27
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will be conducted in three parts. Part A is a dose-escalation study to determine two safe and tolerable doses of ASN001 for men with metastatic castration resistant prostate cancer. Part A will also characterize the pharmacokinetics and pharmacodynamics of the ASN001 through blood sampling. Subjects in Part B will receive one of two doses identified in Part A to determine which one is more effective, and collect additional pharmacokinetic data. Part C is an extension for subjects completing either Part A or B.

Detailed description: Parts A and B will include a screening period (up to 28 days) and a 12-week treatment period. A subject with no serious adverse drug reactions and who is expected to benefit from continued treatment in the opinion of the investigator will have the opportunity to participate in the long-term extension (Part C). If the subject is not a candidate for or chooses not to participate in the long-term extension (Part C), a post-treatment period of 4 weeks will commence that concludes with an end-of-study visit.

Subjects participating in only Part A or Part B will have approximately 9 study site visits over 18 weeks. Part C will include monthly visits to the study site for 9 months. Thereafter, visits will occur every 3 months. A subject with stable disease or response may continue ASN001 treatment with the approval of the investigator; treatment can continue until a subject experiences an intolerable adverse event (AE) or disease progression, withdraws consent or until termination of the study by the sponsor. At the end of treatment, a post-treatment period of 4 weeks will commence that concludes with an end-of-study visit.

Part B of the study will not be completed as enrollment was halted after Part A (Phase 1)

Eligibility criteria: Inclusion Criteria

* Histologically confirmed adenocarcinoma of the prostate.
* Ongoing androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist, or bilateral orchiectomy and serum testosterone level \< 50 ng/dL (\< 0.5 ng/mL, \< 1.7 nmol/L) at screening
* Metastatic disease documented by computed tomography (CT)/magnetic resonance imaging (MRI) or bone scan.
* Progressive disease despite ongoing androgen deprivation therapy.
* Adequate liver, kidney, and bone marrow function
* Life expectancy of at least 3 months
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at screening
* Patients with prior cytotoxic chemotherapy are eligible to participate if they have been progression free for at least 12 months since the initiation of cytotoxic chemotherapy

Exclusion Criteria:

* Patients with rapidly progressive disease who are candidates for other approved therapies such as docetaxel, abiraterone, and enzalutamide.
* Prior therapy with abiraterone, orteronel, ketoconazole, or any other Cytochrome P450 (CYP) 17 lyase inhibitor; enzalutamide or other experimental androgen receptor antagonist; or experimental immunotherapy agent.
* History of impaired adrenal gland function
* Any investigational treatments for any condition within 4 weeks prior to the start of study treatment.
* Therapy with herbal products known to effect PSA, or estrogen within 30 days prior to the start of study medication
* Known gastrointestinal disease or condition that affects the absorption of ASN001, or difficulty swallowing large capsules.
* Use of systemic glucocorticoid (eg, prednisone, dexamethasone) within 14 days prior to the start of study medication
* Major surgery within 30 days of study medication
* Known brain metastasis
* Previous history of another cancer within 5 years, except completely removed basal or squamous cell skin cancer.
* Serious concurrent medical conditions including: serious heart disease, heart conduction abnormalities, persistent infection, uncontrolled psychiatric illness, liver cirrhosis, chronic liver disease, active or symptomatic viral hepatitis, any other condition that may place the subject at an increased risk or confound the results of the study.

Primary outcomes:
measure: Determine the maximum tolerated dose (MTD) of ASN001
timeFrame: First 28 days
Secondary outcomes:
measure: Calculate the pharmacokinetic profile of ASN001
timeFrame: First 29 days
measure: Change in tumor size by CT, MRI or bone scan
timeFrame: 12 weeks
measure: Change in ECOG performance status (score 0 to 5) from baseline as assessed by the investigator
timeFrame: 12 weeks
measure: Time on treatment
timeFrame: 52 weeks
Other outcomes:
measure: Concentration of serum bone-specific alkaline phosphatase (BAP)
timeFrame: 12 weeks
measure: The effect of ASN001 on steroid biosynthesis
timeFrame: 52 weeks
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center, Clark Urology Center
state: California
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Abramson Cancer Center, Hospital of the Univ. of Pennsylvania
state: Pennsylvania
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
Study officials:
affiliation: Asana BioSciences
name: Niranjan Rao, PhD
role: STUDY_DIRECTOR
References: