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

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

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer; Cancer of the Prostate; Neoplasms, Prostate; Prostatic Cancer; Neoplasms, Prostatic; Prostate Neoplasms, Castration-resistant
• Intervention / Treatment: Drug: ASN001: Escalating dose Part A

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)

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center, Clark Urology Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center, Hospital of the Univ. of Pennsylvania
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASN001: Escalating dose Part A; 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; Androgen inhibitor

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of serum bone-specific alkaline phosphatase (BAP)	To evaluate the effects of ASN001 on the concentration of serum bone-specific alkaline phosphatase (BAP)	12 weeks
The effect of ASN001 on steroid biosynthesis	Effects on Luteinizing hormone, follicle stimulating hormone, cortisol, adrenocorticotropic hormone, deoxycorticosterone, corticosterone, dehydroepiandrosterone (DHEA), DHEA sulfate, testosterone and dihydrotestosterone	52 weeks

Collaborators and Investigators

• Sponsor: Asana BioSciences
• Investigators: Study Director: Niranjan Rao, PhD, Asana BioSciences

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2015
• Primary Completion (Actual): July 14, 2017
• Study Completion (Actual): August 17, 2017

Study Registration Dates

• First Submitted: January 13, 2015
• First Submitted That Met QC Criteria: January 23, 2015
• First Posted (Estimate): January 28, 2015

Study Record Updates

• Last Update Posted (Actual): March 7, 2018
• Last Update Submitted That Met QC Criteria: March 6, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplasms; Prostatic Neoplasms
• Other Study ID Numbers: ASN001-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No