Bosutinib in Adult Patients With Recurrent Glioblastoma
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label, Phase 2 Trial of Orally Administered Bosutinib (SKI-606) in Adult Patients With Recurrent Glioblastoma (GBM)|
- Progression-Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]Assess progression-free survival at six months in patients with recurrent glioblastoma at first or second recurrence who are treated with continuous daily dosing of bosutinib (Arm B). Progression-free survival is measured from initiation of study treatment to date of progression.
- Intratumoral Concentration [ Time Frame: 2 years ] [ Designated as safety issue: No ]Assess the intratumoral concentration of bosutinib in recurrent glioblastoma patients who are candidates for surgical re-resection (ARM A).
- Safety Profile [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Overall safety profile will be characterized by type, frequency, severity (as graded by NCI CTCAE), timing and relationship of study therapy of adverse events and laboratory abnormalities. Safety and tolerability will be measured by the proportion of patients who experience Grade 3 or higher Adverse Events that are possibly, probably or definitely related to bosutinib and the number of same Adverse Events per patient. Adverse Events will be summarized by treatment for each arm by the frequency of patients experiencing treatment emergent adverse events.
- Anti-tumor Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]Assess anti-tumor response in patients in Arm B using MacDonald criteria. There are four possible responses: complete response, partial response, stable disease, or progressive disease. Criteria are based on measurements of tumor dimension as visualized with a contrast-enhanced MRI.
|Study Start Date:||April 2011|
|Study Completion Date:||December 2014|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm A
Patients who are surgical candidates. Participants are given oral bosutinib, 400mg daily, for 7-9 days prior to resection. After at least 10 days elapsed post-operatively, bosutinib dosing was resumed.
Other Name: SKI-606
Experimental: Arm B
Patients that are not surgical candidates. Participants are given oral bosutinib, 400 mg daily in 28 day cycles until disease progression, intolerability or withdrawal of consent.
Other Name: SKI-606
- Arm A: Participants will receive daily doses of bosutinib orally for 7-9 days prior to surgery. On the day of the scheduled surgery (either craniotomy or surgical resection as planned by the treating doctor), participants will take the bosutinib within 6-12 hours of the surgery. During the surgery, tissue samples of the tumor will be collected to test the levels of bosutinib in the brain. A contrast-enhanced MRI or CT scan will be done within days after the surgery. Daily dosing of bosutinib will resume after a recovery period of 10 days. From then on, the study will be divided into 28-day cycles.
The following tests/procedures will be performed regularly during cycles of study treatment: medical history; physical exam; blood tests; contrast-enhanced CT or MRI scans (even numbered cycles only).
- Arm B: Participants will receive daily doses of bosutinib. The study is divided int 28-day cycles. There are no breaks from taking bosutinib between treatment cycles. The following tests/procedures will be performed regularly during cycles of study treatment: medical history; physical exam; blood tests; contrast-enhanced CT or MRI scans (even numbered cycles only).
- Participants may continue to receive daily bosutinib until their disease worsens, they experience unmanageable side-effects, or they decide to stop treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01331291
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Dana=Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Tracy Batchelor, MD||Massachusetts General Hospital|