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

Phase 1

Completed

• Conditions: Prostate Cancer
• Interventions: Drug: AT13387; Drug: abiraterone acetate; Drug: Prednisone

• Registration Number: NCT01685268
• Lead Sponsor: Astex Pharmaceuticals, Inc.

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 available

Study Timeline

• Study First Submitted: 2012-08-31
• Study Start: 2012-09
• Study First Submitted QC: 2012-09-11
• Study First Posted: 2012-09-14
• Primary Completion: 2014-07
• Study Completion: 2014-12
• Disposition First Submitted: 2016-01-08
• Disposition First Submitted QC: 2016-01-08
• Disposition First Posted: 2016-02-05
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-01
• Last Update Posted: 2024-08-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 49

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A, Regimen 1	AT13387	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.
Part A, Regimen 2	AT13387	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.
Part A, Regimen 1	abiraterone acetate	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.
Part A, Regimen 1	Prednisone	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.
Part A, Regimen 2	Prednisone	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.
Part A, Regimen 2	abiraterone acetate	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.

Primary Outcome Measures

Name	Time	Method
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.	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.	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

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamics of combination treatment of AT13387 and abiraterone.	24 months	CTC enumeration and characterization every 4 weeks.
Overall survival	24 months	Overall survival as measured in weeks
Pharmacokinetics of combination treatment of AT13387 and abiraterone.	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
Progression free survival	24 months	Assessment of progression free survival as measured by weeks

Trial Locations

Locations (32)

University of California, Los Angeles Institute of Urologic Oncology; 🇺🇸 Los Angeles, California, United States

Stanford Cancer Center; 🇺🇸 Stanford, California, United States

Holy Cross Hospital; 🇺🇸 Fort Lauderdale, Florida, United States

Florida Cancer Specialists-Fort Myers; 🇺🇸 Fort Myers, Florida, United States

Lakeland Regional Cancer Center; 🇺🇸 Lakeland, Florida, United States

Southern Illinois University School of Medicine; 🇺🇸 Springfield, Illinois, United States

University of Maryland, Greenebaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Center for Cancer & Blood Disorders; 🇺🇸 Bethesda, Maryland, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

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