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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01685268
First received: August 31, 2012
Last updated: May 8, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention Phase
Prostate Cancer
Drug: AT13387 and abiraterone
Drug: AT13387 alone
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Astex Pharmaceuticals:

Primary Outcome Measures:
  • 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. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    • 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

  • 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. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    • 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


Secondary Outcome Measures:
  • Pharmacokinetics of combination treatment of AT13387 and abiraterone. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    • 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

  • Pharmacodynamics of combination treatment of AT13387 and abiraterone. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    CTC enumeration and characterization every 4 weeks.

  • Progression free survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Assessment of progression free survival as measured by weeks

  • Overall survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Overall survival as measured in weeks


Estimated Enrollment: 164
Study Start Date: September 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AT13387 and abiraterone
Part A: AT13387 IV with abiraterone 1000 mg QD and prednisone or prednisolone 5 mg BID
Drug: AT13387 and abiraterone
Parallel
Other Name: AT13387 and Zytiga
Experimental: AT13387 alone or in combination with abiraterone acetate
Part B: AT13387 alone or AT13387 with abiraterone acetate 1000 mg PO
Drug: AT13387 alone
Parallel
Other Name: AT13387

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01685268

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

No publications provided

Responsible Party: Astex Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01685268     History of Changes
Other Study ID Numbers: AT13387-04
Study First Received: August 31, 2012
Last Updated: May 8, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Astex Pharmaceuticals:
Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 21, 2014