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

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

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).

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: AT13387; Drug: abiraterone acetate; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2L 4MI
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
• Spain
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal
• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • Brighton & Sussex University Hospitals NHS Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre Cancer Center
  • Guildford, United Kingdom, GU2 7XP
    • University of Surrey
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • London, United Kingdom
    • Royal Marsden Foundation Trust Instute of Cancer Researrch
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital NHS Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals
  • Southampton, United Kingdom, S016 6YD
    • University Hospital Southampton
  • Wirral, United Kingdom, CH63 4JY
    • Clatterbridge Cancer Centre NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90024
      • University of California, Los Angeles Institute of Urologic Oncology
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists-Fort Myers
    • Lakeland, Florida, United States, 33805
      • Lakeland Regional Cancer Center
  • Illinois
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Greenebaum Cancer Center
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer & Blood Disorders
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance, Inc.
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • The West Clinic
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialists, PLLC

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A, Regimen 1; AT13387 given as a 1-hr IV infusion at a starting dose of 220 mg/m2 once weekly for 3 weeks in a 4-week cycle, in combination with abiraterone acetate 1000 mg by mouth (PO) daily (QD) and prednisone or prednisolone 5 mg PO twice daily.	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.; Other Names: onalespib; Drug: abiraterone acetate; 1000 mg PO daily.; Drug: Prednisone; 5 mg PO twice daily.; Other Names: prednisolone
Experimental: Part A, Regimen 2; At13387 administered as a 1-hr IV infusion at a starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle, in combination with abiraterone acetate 1000 mg by mouth (PO) daily (QD) and prednisone or prednisolone 5 mg PO twice daily.	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.; Other Names: onalespib; Drug: abiraterone acetate; 1000 mg PO daily.; Drug: Prednisone; 5 mg PO twice daily.; Other Names: prednisolone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Pharmacodynamics of combination treatment of AT13387 and abiraterone.	CTC enumeration and characterization every 4 weeks.	24 months
Progression free survival	Assessment of progression free survival as measured by weeks	24 months
Overall survival	Overall survival as measured in weeks	24 months

Collaborators and Investigators

• Sponsor: Astex Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Johann De Bono, MD, Royal Marsden Foundation Trust Institute of Cancer Research

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: August 31, 2012
• First Submitted That Met QC Criteria: September 11, 2012
• First Posted (Estimated): September 14, 2012

Study Record Updates

• Last Update Posted (Actual): August 2, 2024
• Last Update Submitted That Met QC Criteria: August 1, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Prostate Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Prednisolone; Prednisone; Abiraterone Acetate
• Other Study ID Numbers: AT13387-04