PCI-24781 in Combination With Doxorubicin to Treat Sarcoma
The purpose of this research study is to determine the safety and maximum tolerated dose of PCI-24781 that can be given safely with doxorubicin (phase I) and the safety and efficacy of PCI-24781 when used in combination with doxorubicin (phase II) in patients with advanced sarcomas. The study drug, PCI-24781, is believed to regulate genes involved in tumor cell growth. The other study drug, doxorubicin, is considered a standard chemotherapeutic treatment for advanced sarcoma patients. We hypothesize that combining PCI-24781 with doxorubicin can overcome chemoresistance to doxorubicin.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of PCI-24781 in Combination With Doxorubicin for Treatment of Advanced Sarcomas Following Failure or Prior Anthracycline Therapy|
- Phase I: To determine the MTD (and/or recommended phase II dose) of PCI-24781 when given orally twice a daily for 5 days in combination with doxorubicin. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Phase II: To assess the response rate of PCI-24781 at the MTD when given with doxorubicin in patients whose disease has failed to be controlled despite prior therapy. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Phase I: To evaluate the safety and tolerability of PCI-24781 in combination with doxorubicin. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Phase I: To determine the pharmacokinetic and pharmacodynamic parameters of PCI-24781 in combination with doxorubicin in sarcoma patients. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Phase I: To measure evidence of antitumor activity of PCI-24781 in combination with doxorubicin in this patient population. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Phase II: Assess the duration of response and rate of progression-free survival at 6 months in participants who received PCI-24781/doxorubicin combination administration. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||February 2009|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
PCI-24781 in combination with doxorubicin
Capsules taken orally for 5 consecutive days starting on Day 1 of each 3 week cycle
Other Name: PCI24781Drug: Doxorubicin
Administered intravenously on Day 4 of each 3 week cycle
Other Name: Adriamycin
- In the phase I portion of the study, since we are looking for the highest dose of PCI-24781 that can be administered safely without severe or unmanageable side effects in participants that have advanced sarcoma, not everyone who participates in this research study will receive the same dose of PCI-24871.
- Each treatment cycle is 3 weeks (21 days). Participants will take capsules of PCI-24871 for five consecutive days starting on Day 1 of each 3 week cycle. On Day 4 of each cycle, participants will come to the clinic to receive doxorubicin intravenously.
- At specific time intervals, participants will return to the clinic for the following tests and procedures: physical examination, vital signs, blood tests, urine test, EKG, assessment of the tumor by CT scan, and an ECHO or MUGA.
- Participants may remain on the study for a maximum of 6 cycles (about 4-5 months). After the last cycle, as long as the participant is showing benefit, they may elect to continue taking PCI-24781 alone, in which case they will continue in this research study until there is evidence of their tumor growing.
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Edwin Choy, MD, PhD||Massachusetts General Hospital|