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

  Show 32 Study Locations
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 Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on August 19, 2014