Clinical trial NCT01685268: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Keywords: Prostate Cancer
Lead sponsor: Astex Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-09-14
Enrollment: 49
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: 12 months
measure: 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.
timeFrame: 12 months
Secondary outcomes:
measure: Pharmacokinetics of combination treatment of AT13387 and abiraterone.
timeFrame: 24 months
measure: Pharmacodynamics of combination treatment of AT13387 and abiraterone.
timeFrame: 24 months
measure: Progression free survival
timeFrame: 24 months
measure: Overall survival
timeFrame: 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles Institute of Urologic Oncology
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists-Fort Myers
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center
state: Florida
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Cancer Center
state: Maryland
city: Bethesda
country: United States
facility: Center for Cancer & Blood Disorders
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Lake Success
country: United States
facility: Clinical Research Alliance, Inc.
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Tacoma
country: United States
facility: Northwest Medical Specialists, PLLC
state: Washington
city: Montreal
country: Canada
facility: Centre hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Brighton
country: United Kingdom
facility: Brighton & Sussex University Hospitals NHS Trust
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center
city: Guildford
country: United Kingdom
facility: University of Surrey
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: London
country: United Kingdom
facility: Royal Marsden Foundation Trust Instute of Cancer Researrch
city: Manchester
country: United Kingdom
facility: The Christie Hospital NHS Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
city: Wirral
country: United Kingdom
facility: Clatterbridge Cancer Centre NHS Foundation Trust
Study officials:
References: