A Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate

Prostate Cancer Clinical Trial

Official title:

A Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate in the Treatment of Castration-Resistant Prostate Cancer (CRPC) no Longer Responding to Abiraterone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01685268
• Other study ID #: AT13387-04
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 31, 2012
• Last updated: September 6, 2016
• Start date: September 2012
• Est. completion date: December 2014

Study information

• Verified date: September 2016
• Source: Astex Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

A 2-part, Phase 1-2, open-label, parallel group, randomized study in patients with Castration-Resistant Prostate Cancer (CRPC) who are no longer responding to treatment with abiraterone and steroids. In Part A (Phase 1), patients will continue to receive the same doses of abiraterone and steroids they were receiving prior to study entry and will be randomized to receive 1 of 2 different treatment regimens of AT13387 in combination with abiraterone. Once the best regimen is established in Part A, based on safety and antitumor activity, patients will be randomized to the selected treatment regimen and dose of AT13387 in combination with abiraterone or AT13387 alone in Part B (Phase 2).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion:

1. Must have prostate cancer

2. Have received prior castration by orchiectomy and/or hormone therapy

3. Males >18 years of age

4. Normal activity level for self care

5. Have been receiving abiraterone therapy with a steroid for =1 month

6. Have disease progression on abiraterone as defined by either PSA progression, radiographic or bone progression

7. Have adequate bone marrow, liver and kidney function

8. Must be willing to provide pre-existing tumor samples, if this material exists. If pre-existing samples are not available, a sample must be obtained during screening

9. Must be willing and able to provide written informed consent and comply with the protocol and study procedures

Exclusion:

1. Prior anti-cancer treatment with any Heat Shock Protein 90 (HSP90) inhibitor or histone deacetylase (HDAC) inhibitor compound

2. Have received chemotherapy within 4 weeks prior to receiving study drug

3. Prior prostate surgery or radiotherapy within 4 weeks from the first dose of study drug

4. Hypersensitivity to AT13387 or other components of the drug product

5. Treatment with any investigational drug within 4 weeks prior to the first dose of study drug

6. Severe systemic diseases or active uncontrolled infections

7. Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors

8. Abnormal heart function

9. Other cancer except for adequately treated basal cell or squamous cell carcinoma of the skin, or superficial bladder cancer, or other cancer from which the subject has been disease-free for at least 3 years;

10. No known brain or CNS involvement

11. Unable to receive corticosteroids or history of pituitary or adrenal dysfunction

12. Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• AT13387
Regimen 1: AT13387, given as 1-hr intravenous infusion at starting dose of 220 mg/m2 once weekly for 3 weeks in a 4-week cycle. Regimen 2: AT13387, given as 1-hr IV infusion at starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle.
• abiraterone acetate
1000 mg PO daily.
• Prednisone
5 mg PO twice daily.

Locations

Country	Name	City	State
Canada	Centre hospitalier de l'Universite de Montreal (CHUM)	Montreal	Quebec
Spain	Centro Integral Oncologico Clara Campal	Madrid
United Kingdom	Brighton & Sussex University Hospitals NHS Trust	Brighton
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Velindre Cancer Center	Cardiff
United Kingdom	University of Surrey	Guildford
United Kingdom	Charing Cross Hospital	London
United Kingdom	Royal Marsden Foundation Trust Instute of Cancer Researrch	London
United Kingdom	The Christie Hospital NHS Trust	Manchester
United Kingdom	Nottingham University Hospitals	Nottingham
United Kingdom	University Hospital Southampton	Southampton
United Kingdom	Clatterbridge Cancer Centre NHS Foundation Trust	Wirral
United States	University of Maryland, Greenebaum Cancer Center	Baltimore	Maryland
United States	Center for Cancer & Blood Disorders	Bethesda	Maryland
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Cleveland Clinic	Cleveland	Ohio
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Florida Cancer Specialists-Fort Myers	Fort Myers	Florida
United States	Clinical Research Alliance, Inc.	Lake Success	New York
United States	Lakeland Regional Cancer Center	Lakeland	Florida
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	University of California, Los Angeles Institute of Urologic Oncology	Los Angeles	California
United States	The West Clinic	Memphis	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Washington University School of Medicine	St. Louis	Missouri
United States	Stanford Cancer Center	Stanford	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Northwest Medical Specialists, PLLC	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Astex Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Safety and tolerability of the combination of AT13387 and abiraterone and to select the most promising treatment regimen in CRPC patients who are no longer responding to treatment with abiraterone alone.	Number of patients with adverse events; Change in prostate specific antigen measurement and circulating tumor cell count every 4 weeks; Change in tumor measurements by RECIST 1.1 every 12 weeks	12 months	Yes
Primary	Part B: Compare the antitumor activity (response rate per the Prostate Cancer Working Group 2 [PCWG2]) between single-agent AT13387 and combination of AT13387 plus abiraterone in patients who are no longer responding to treatment with abiraterone alone.	Change in prostate specific antigen measurement and circulating tumor cell count every 4 weeks; Change in tumor measurements by RECIST 1.1 every 12 weeks	12 months	No
Secondary	Pharmacokinetics of combination treatment of AT13387 and abiraterone.	Area under the plasma concentration versus time curve (AUC) of AT13387 and abiraterone alone and in combination by Week 4; Maximum concentration (Cmax) of AT13387 and abiraterone alone and in combination by Week 4	24 months	No
Secondary	Pharmacodynamics of combination treatment of AT13387 and abiraterone.	CTC enumeration and characterization every 4 weeks.	24 months	No
Secondary	Progression free survival	Assessment of progression free survival as measured by weeks	24 months	No
Secondary	Overall survival	Overall survival as measured in weeks	24 months	No