Study of AUY922 in Metastatic Pancreatic Cancer Who Are Resistant to First Line Chemotherapy
This is a phase II study to see how useful study drug AUY922 is in patients with metastatic pancreatic cancer who have received or are intolerant to first-line chemotherapy.
AUY922 is an intravenous drug that blocks a protein called heat shock protein 90 (Hsp90). Hsp90 works by keeping a number of other proteins stable and active, including many proteins that are involved in tumor growth and death. When Hsp90 is blocked from working, it is believed that many of the other proteins that it stabilizes will also be blocked, which will cause tumor growth to slow or stop.
During the study, patients will visit the clinic once a week, every 4 week cycles to receive AUY922 intravenously and to have tests and procedures done. As part of the study, archived tumor tissue will be collected and patients will be asked to have blood samples taken for pharmacokinetic testing. Patients will be invited to take part in an optional banking of blood samples for future studies.
The primary hypothesis of this study is that AUY922 improves disease control rate compared with what would be expected from best supportive care.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Single Arm Study of AUY922 in Patients With Metastatic Pancreatic Adenocarcinoma Who Are Resistant to First Line Chemotherapy|
- Determine anti-tumor activity using disease control rate [ Time Frame: 18-20 months ] [ Designated as safety issue: No ]Disease control rate is defined as objective response rate plus prolonged stable disease (≥16 weeks).
- Determine safety and tolerability of AUY922 [ Time Frame: 18-20 months ] [ Designated as safety issue: Yes ]Number of participants with adverse events. Frequency, severity and grading of adverse events. Number of participants requiring dose reductions.
- Determine antitumor activity of AUY922 using duration of time from start of treatment to time of progression or death (progression-free survival). [ Time Frame: 18-20 months ] [ Designated as safety issue: No ]
- Determine antitumor activity of AUY922 using median time from date of enrollment to date of death (overall survival) [ Time Frame: 18-20 months ] [ Designated as safety issue: No ]
- Determine antitumor activity of AUY922 using stable disease duration [ Time Frame: 18-20 months ] [ Designated as safety issue: No ]
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||August 2013|
|Estimated Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
AUY922 is a solution for intravenous administration Dose: 70 mg/m2 over 1 hour, weekly
This is a single arm open label Phase II clinical trial evaluating the efficacy of AUY922 in patients with advanced pancreatic cancer who have been previously treated with or are intolerant to first line chemotherapy. The primary objective is to assess the efficacy of this agent by assessing the disease control rate (DCR) (objective response plus prolonged stable disease (>16 weeks).
The current standard therapy for patients who have advanced, metastatic or inoperable pancreatic cancer previously treated with or intolerant to first line chemotherapy is best supportive care. New treatment options are urgently needed.
Heat shock protein 90 (HSP90) is an ATP-dependent molecular chaperone protein involved in the stabilization of a number of membrane and intracellular proteins including HER2, BCR-ABL, C-SRC, EGFR, RAF, VEGFR, AKT, and RAS. Many of these proteins are highly expressed in pancreatic adenocarcinoma.
AUY922 is a novel isoxazole-based HSP90 inhibitor. AUY922 acts by inhibiting HSP90 ATPase activity (IC50 of 30 nm) and preventing the formation of a multichaperone complex between HSP90 and other heat shock proteins. This then prevents HSP90 from performing its functions on client proteins.
|Contact: Malcolm J. Moore, M.D.||(416) email@example.com|
|Princess Margaret Hospital||Recruiting|
|Toronto, Ontario, Canada, M5G 2M9|
|Contact: Katie Allen, MSc (416) 946-4501 ext 3910 firstname.lastname@example.org|
|Contact: June Hui, Hon.B.Sc. (416) 946-4501 ext 3185 email@example.com|
|Principal Investigator: Malcolm Moore, M.D.|
|Principal Investigator:||Malcolm J. Moore, M.D.||Princess Margaret Hospital, Canada|