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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02349139
• Other study ID #: ASN001-101
• Status: Terminated
• Phase: Phase 1
• First received: January 13, 2015
• Last updated: March 6, 2018
• Start date: January 19, 2015
• Est. completion date: August 17, 2017

Study information

• Verified date: March 2018
• Source: Asana BioSciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: August 17, 2017
• Est. primary completion date: July 14, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• ASN001: Escalating dose Part A
Androgen inhibitor

Locations

Country	Name	City	State
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	UCLA Medical Center, Clark Urology Center	Los Angeles	California
United States	Abramson Cancer Center, Hospital of the Univ. of Pennsylvania	Philadelphia	Pennsylvania
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Asana BioSciences

Country where clinical trial is conducted

United States, 

Outcome

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