Safety, Preliminary Efficacy and Pharmacokinetics of ASN001 in Metastatic Castrate Resistant Prostate Cancer

Study Overview
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Brief Summary
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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
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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)

Official Title
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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

Conditions
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Prostate Cancer, Cancer of the Prostate, Neoplasms, Prostate, Prostatic Cancer, Neoplasms, Prostatic, Prostate Neoplasms, Castration-resistant

Intervention / Treatment
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* Drug: ASN001: Escalating dose Part A


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASN001: Escalating dose Part A<br>The dose of ASN001 will be based on the assigned study group. The initial dose level of ASN001 will be 50 mg daily. After a safety review, the dose may be escalated for the next group of subjects. Additional dose levels are 100 mg, 200 mg, 300 mg, and 400 mg. | Drug: ASN001: Escalating dose Part A<br>* Androgen inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose (MTD) of ASN001 | The MTD will be determined by evaluating the number of subjects with treatment related dose limiting toxicity. | First 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calculate the pharmacokinetic profile of ASN001 | Pharmacokinetic Parameters | First 29 days | 
| Change in tumor size by CT, MRI or bone scan | measure of efficacy | 12 weeks | 
| Change in ECOG performance status (score 0 to 5) from baseline as assessed by the investigator | Measure of efficacy | 12 weeks | 
| Time on treatment | Measure of safety, tolerability and preliminary efficacy | 52 weeks |