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

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ClinicalTrials.gov Identifier: NCT01685268
Recruitment Status : Completed
First Posted : September 14, 2012
Last Update Posted : September 8, 2016
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE August 31, 2012
First Posted Date  ICMJE September 14, 2012
Last Update Posted Date September 8, 2016
Study Start Date  ICMJE September 2012
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2012)
  • 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 ]
    • 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 ]
    • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01685268 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2012)
  • Pharmacokinetics of combination treatment of AT13387 and abiraterone. [ Time Frame: 24 months ]
    • 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 ]
    CTC enumeration and characterization every 4 weeks.
  • Progression free survival [ Time Frame: 24 months ]
    Assessment of progression free survival as measured by weeks
  • Overall survival [ Time Frame: 24 months ]
    Overall survival as measured in weeks
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate
Official Title  ICMJE 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
Brief 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • 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 Name: onalespib
  • Drug: abiraterone acetate
    1000 mg PO daily.
  • Drug: Prednisone
    5 mg PO twice daily.
    Other Name: prednisolone
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: AT13387
    • Drug: abiraterone acetate
    • Drug: Prednisone
  • 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.
    Interventions:
    • Drug: AT13387
    • Drug: abiraterone acetate
    • Drug: Prednisone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 13, 2015)
49
Original Estimated Enrollment  ICMJE
 (submitted: September 11, 2012)
164
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01685268
Other Study ID Numbers  ICMJE AT13387-04
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Astex Pharmaceuticals
Study Sponsor  ICMJE Astex Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Johann De Bono, MD Royal Marsden Foundation Trust Institute of Cancer Research
PRS Account Astex Pharmaceuticals
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP