MK-2206 is a newly discovered drug that may slow or stop cancer growth. This drug has been
used in other research studies, and information from those other research studies suggests
that MK-2206 may help to slow or stop the growth of malignant gliomas. In addition, MK-2206
has the capacity to cross the blood-brain barrier. The blood-brain barrier (BBB) is a
separation of circulating blood and cerebrospinal fluid (CSF) in the central nervous system
(CNS); and although it serves as a protective barrier, it can often interfere with
potentially beneficial treatments reaching the brain successfully. Therefore, the
investigators hope that because MK-2206 can successfully cross the blood-brain barrier, it
will be more effective in patients. The purpose of this study is to see how well MK-2206
works in patients with malignant gliomas and will be conducted in two parts: Part 1 and Part
2.
Part 1 of the study will investigate the effects of MK-2206 on Akt signaling in tumor tissue.
Ten patients with recurrent GBM who require reoperation will receive a short pre-operative
course of MK-2206. After recovery from surgery, patients will resume MK-2206 until disease
progression or the development of unacceptable toxicities. Part 2 of this trial will be
initiated only AFTER analysis of Part 1 data shows drug penetration into tumor tissue; if
there is no significant drug penetration into the tumor and/or there is no reduction of pAkt
levels, progression to Part 2 of the trial will be halted. The primary goal of Part 2 is to
determine the therapeutic efficacy of MK-2206 as measured by 6-month progression-free
survival (PFS6). In Part 2, 40 participants with GBM and 18 with anaplastic glioma will be
treated with MK-2206 weekly at a dose selected on the basis of an ongoing phase 1 study.
Treatment duration will be measured in 4-week cycles. Participants will remain on treatment
until tumor progression, as long as there are no unacceptable toxicities. Responses will be
assessed by clinical examinations every 4 weeks and MRI scans every 8 weeks.
Phase:
Phase 2
Details
Lead Sponsor:
Dana-Farber Cancer Institute
Collaborators:
Beth Israel Deaconess Medical Center Brigham and Women's Hospital Massachusetts General Hospital Memorial Sloan Kettering Cancer Center Merck Sharp & Dohme Corp. University of California, Los Angeles