Back to resultsA Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AT13387
abiraterone acetate
Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Prostate Cancer
Eligibility Criteria
Inclusion:
- Must have prostate cancer
- Have received prior castration by orchiectomy and/or hormone therapy
- Males >18 years of age
- Normal activity level for self care
- Have been receiving abiraterone therapy with a steroid for ≥1 month
- Have disease progression on abiraterone as defined by either PSA progression, radiographic or bone progression
- Have adequate bone marrow, liver and kidney function
- 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
- Must be willing and able to provide written informed consent and comply with the protocol and study procedures
Exclusion:
- Prior anti-cancer treatment with any Heat Shock Protein 90 (HSP90) inhibitor or histone deacetylase (HDAC) inhibitor compound
- Have received chemotherapy within 4 weeks prior to receiving study drug
- Prior prostate surgery or radiotherapy within 4 weeks from the first dose of study drug
- Hypersensitivity to AT13387 or other components of the drug product
- Treatment with any investigational drug within 4 weeks prior to the first dose of study drug
- Severe systemic diseases or active uncontrolled infections
- Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors
- Abnormal heart function
- 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;
- No known brain or CNS involvement
- Unable to receive corticosteroids or history of pituitary or adrenal dysfunction
- Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus
Sites / Locations
- University of California, Los Angeles Institute of Urologic Oncology
- Stanford Cancer Center
- Holy Cross Hospital
- Florida Cancer Specialists-Fort Myers
- Lakeland Regional Cancer Center
- Southern Illinois University School of Medicine
- University of Maryland, Greenebaum Cancer Center
- Center for Cancer & Blood Disorders
- Washington University School of Medicine
- University of Nebraska Medical Center
- Comprehensive Cancer Centers of Nevada
- Roswell Park Cancer Institute
- Clinical Research Alliance, Inc.
- Columbia University Medical Center
- Memorial Sloan Kettering Cancer Center
- SUNY Upstate Medical University
- Cleveland Clinic
- University of Pittsburgh Medical Center
- The West Clinic
- Northwest Medical Specialists, PLLC
- Centre hospitalier de l'Universite de Montreal (CHUM)
- Centro Integral Oncologico Clara Campal
- Brighton & Sussex University Hospitals NHS Trust
- Cambridge University Hospitals NHS Foundation Trust
- Velindre Cancer Center
- University of Surrey
- Charing Cross Hospital
- Royal Marsden Foundation Trust Instute of Cancer Researrch
- The Christie Hospital NHS Trust
- Nottingham University Hospitals
- University Hospital Southampton
- Clatterbridge Cancer Centre NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part A, Regimen 1
Part A, Regimen 2
Arm Description
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.
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.
Outcomes
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.
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.
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.
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.
CTC enumeration and characterization every 4 weeks.
Progression free survival
Assessment of progression free survival as measured by weeks
Overall survival
Overall survival as measured in weeks
Full Information
NCT ID
NCT01685268
First Posted
August 31, 2012
Last Updated
September 6, 2016
Sponsor
Astex Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01685268
Brief Title
A Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astex Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A, Regimen 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Part A, Regimen 2
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AT13387
Other Intervention Name(s)
onalespib
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
abiraterone acetate
Intervention Description
1000 mg PO daily.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
prednisolone
Intervention Description
5 mg PO twice daily.
Primary Outcome Measure Information:
Title
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.
Description
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
Time Frame
12 months
Title
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.
Description
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
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Pharmacokinetics of combination treatment of AT13387 and abiraterone.
Description
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
Time Frame
24 months
Title
Pharmacodynamics of combination treatment of AT13387 and abiraterone.
Description
CTC enumeration and characterization every 4 weeks.
Time Frame
24 months
Title
Progression free survival
Description
Assessment of progression free survival as measured by weeks
Time Frame
24 months
Title
Overall survival
Description
Overall survival as measured in weeks
Time Frame
24 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion:
Must have prostate cancer
Have received prior castration by orchiectomy and/or hormone therapy
Males >18 years of age
Normal activity level for self care
Have been receiving abiraterone therapy with a steroid for ≥1 month
Have disease progression on abiraterone as defined by either PSA progression, radiographic or bone progression
Have adequate bone marrow, liver and kidney function
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
Must be willing and able to provide written informed consent and comply with the protocol and study procedures
Exclusion:
Prior anti-cancer treatment with any Heat Shock Protein 90 (HSP90) inhibitor or histone deacetylase (HDAC) inhibitor compound
Have received chemotherapy within 4 weeks prior to receiving study drug
Prior prostate surgery or radiotherapy within 4 weeks from the first dose of study drug
Hypersensitivity to AT13387 or other components of the drug product
Treatment with any investigational drug within 4 weeks prior to the first dose of study drug
Severe systemic diseases or active uncontrolled infections
Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors
Abnormal heart function
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;
No known brain or CNS involvement
Unable to receive corticosteroids or history of pituitary or adrenal dysfunction
Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johann De Bono, MD
Organizational Affiliation
Royal Marsden Foundation Trust Institute of Cancer Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, Los Angeles Institute of Urologic Oncology
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Facility Name
Stanford Cancer Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Holy Cross Hospital
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Facility Name
Florida Cancer Specialists-Fort Myers
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33916
Country
United States
Facility Name
Lakeland Regional Cancer Center
City
Lakeland
State/Province
Florida
ZIP/Postal Code
33805
Country
United States
Facility Name
Southern Illinois University School of Medicine
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
Facility Name
University of Maryland, Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Center for Cancer & Blood Disorders
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Clinical Research Alliance, Inc.
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
The West Clinic
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
Northwest Medical Specialists, PLLC
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Centre hospitalier de l'Universite de Montreal (CHUM)
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4MI
Country
Canada
Facility Name
Centro Integral Oncologico Clara Campal
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Brighton & Sussex University Hospitals NHS Trust
City
Brighton
ZIP/Postal Code
BN2 5BE
Country
United Kingdom
Facility Name
Cambridge University Hospitals NHS Foundation Trust
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
Velindre Cancer Center
City
Cardiff
ZIP/Postal Code
CF14 2TL
Country
United Kingdom
Facility Name
University of Surrey
City
Guildford
ZIP/Postal Code
GU2 7XP
Country
United Kingdom
Facility Name
Charing Cross Hospital
City
London
ZIP/Postal Code
W6 8RF
Country
United Kingdom
Facility Name
Royal Marsden Foundation Trust Instute of Cancer Researrch
City
London
Country
United Kingdom
Facility Name
The Christie Hospital NHS Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Nottingham University Hospitals
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Facility Name
University Hospital Southampton
City
Southampton
ZIP/Postal Code
S016 6YD
Country
United Kingdom
Facility Name
Clatterbridge Cancer Centre NHS Foundation Trust
City
Wirral
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate
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