NCT01685268

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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
49

participants targeted

Target at P50-P75 for phase_1 prostate-cancer

Timeline
Completed

Started Sep 2012

Shorter than P25 for phase_1 prostate-cancer

Geographic Reach
4 countries

32 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 31, 2012

Completed
1 day until next milestone

Study Start

First participant enrolled

September 1, 2012

Completed
13 days until next milestone

First Posted

Study publicly available on registry

September 14, 2012

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2014

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2014

Completed
Last Updated

August 2, 2024

Status Verified

August 1, 2024

Enrollment Period

1.8 years

First QC Date

August 31, 2012

Last Update Submit

August 1, 2024

Conditions

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

  • 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

    12 months

  • 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

    12 months

Secondary Outcomes (4)

  • Pharmacokinetics of combination treatment of AT13387 and abiraterone.

    24 months

  • Pharmacodynamics of combination treatment of AT13387 and abiraterone.

    24 months

  • Progression free survival

    24 months

  • Overall survival

    24 months

Study Arms (2)

Part A, Regimen 1

EXPERIMENTAL

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.

Drug: AT13387Drug: abiraterone acetateDrug: Prednisone

Part A, Regimen 2

EXPERIMENTAL

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.

Drug: AT13387Drug: abiraterone acetateDrug: Prednisone

Interventions

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.

Also known as: onalespib
Part A, Regimen 1Part A, Regimen 2

1000 mg PO daily.

Part A, Regimen 1Part A, Regimen 2

5 mg PO twice daily.

Also known as: prednisolone
Part A, Regimen 1Part A, Regimen 2

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (32)

University of California, Los Angeles Institute of Urologic Oncology

Los Angeles, California, 90024, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Florida Cancer Specialists-Fort Myers

Fort Myers, Florida, 33916, United States

Location

Lakeland Regional Cancer Center

Lakeland, Florida, 33805, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

University of Maryland, Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Center for Cancer & Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Clinical Research Alliance, Inc.

Lake Success, New York, 11042, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

Northwest Medical Specialists, PLLC

Tacoma, Washington, 98405, United States

Location

Centre hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, H2L 4MI, Canada

Location

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Brighton & Sussex University Hospitals NHS Trust

Brighton, BN2 5BE, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Velindre Cancer Center

Cardiff, CF14 2TL, United Kingdom

Location

University of Surrey

Guildford, GU2 7XP, United Kingdom

Location

Charing Cross Hospital

London, W6 8RF, United Kingdom

Location

Royal Marsden Foundation Trust Instute of Cancer Researrch

London, United Kingdom

Location

The Christie Hospital NHS Trust

Manchester, M20 4BX, United Kingdom

Location

Clatterbridge Cancer Centre NHS Foundation Trust

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Nottingham University Hospitals

Nottingham, NG5 1PB, United Kingdom

Location

University Hospital Southampton

Southampton, S016 6YD, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

(2,4-dihydroxy-5-isopropylphenyl)-(5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl)methanoneAbiraterone AcetatePrednisonePrednisolone

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

AndrostenesAndrostanesSteroidsFused-Ring CompoundsPolycyclic CompoundsPregnadienediolsPregnadienesPregnanesPregnadienetriols

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 31, 2012

First Posted

September 14, 2012

Study Start

September 1, 2012

Primary Completion

July 1, 2014

Study Completion

December 1, 2014

Last Updated

August 2, 2024

Record last verified: 2024-08

Locations