MK-2206 for Recurrent Malignant Glioma
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of MK-2206 for Recurrent Malignant Glioma|
- Part 1: Akt inhibition [ Time Frame: 2 years ] [ Designated as safety issue: No ]Quantitative pAkt analysis on post-treatment frozen tumor tissue. Equal or more than half of the specimens must demonstrate an absolute pAkt level that is consistent with adequated pAkt inhibition; this threshold has been determined by Merck based on data from prior phase I solid tumor re-biopsy studies.
- Part 1: MK-2206 levels in tumor tissue [ Time Frame: 2 years ] [ Designated as safety issue: No ]The level of MK-2206 in tumor tissue.
- Part 2: Therapeutic efficacy [ Time Frame: 3 years ] [ Designated as safety issue: No ]Determine the therapeutic efficacy of MK-2206 as measured by progression-free survival at 6 months.
Experimental: Part 1
Patients with recurrent glioblastoma multiforme (GBM) who require reoperation.
Taken orally once a week
Experimental: Part 2
Participants with GBM and with anaplastic glioma
Taken orally once a week
- Participants will have the following tests and procedures within 2 days before the first dose of MK-2206: medical history, physical examination, blood tests, urine tests and EKG.
- Participants in Part 2 of this research study may also have optional FDG-PET imaging done. If the participant agrees, they will have two PET scans performed; one within a week before beginning study drug, and another within 3 days after starting study drug.
- Participants in Part 1 will take MK-2206 orally prior to surgery on days 1-8 (with surgery after the MK-2206 dose on day 8). They will have an EKG within 4-8 hours after their first dose of MK-2206, and again on Day 8. During surgery, a sample of the tumor will be taken for research. The tumor tissue will be analyzed to measure the level of MK-2206 in the tumor and to study the effect of the drug on the tumor. Genetic tests will be done on the tumor tissue to determine if the tumor's genetic profile can predict response to treatment. You will also have 3 teaspoons of blood drawn to measure the level of MK-2206 in the blood. An assessment of the participant's tumor by MRI or CT scan will be done within 96 hours of surgery to determine how much of the tumor has been removed. One to 4 weeks after surgery (within 14 days of the last MRI/CT scan), MK-2206 treatment will restart at the same schedule as before surgery (weekly dosing). Within 2 days prior to restarting MK-2206 the following tests and procedures must be completed: medical history, physical examination, blood tests, urine test and EKG.
- Participants in both groups will receive MK-2206 by mouth once a week (Days 1, 8, 15, and 22). Participants will receive an EKG within 4-8 hours after their first dose of MK-2206 (for Part 1 participants, this is day 1 pre-surgery; for Part 2 participants, this is day 1 of the first cycle of treatment). Participants will receive an EKG weekly during their first cycle of treatment with MK-2206. The following tests and procedures are required within 2 days before the start of each subsequent 4-week cycle of MK-2206 treatment: medical history, physical examination, blood tests, urine test, and EKG. Each treatment cycle lasts 4 weeks during which time participants will be taking the study drug once a week. In addition, patients will also need the following tests/procedures performed during treatment cycles: medical history and physical examination on Day 15 (+/- 2 days) of Cycles 1 and 2 and blood tests weekly during Cycle 1 and on Day 15 (+/- 2 days) of cycle 2.
- Assessments of the tumor by MRI will be performed within one week prior to the start of each odd-numbered cycle, starting with cycle 3.
- Participants can continue to receive study drug until their disease worsens or develop unacceptable side effects.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01249105
|United States, California|
|UCLA Medical Center|
|Los Angeles, California, United States, 90095|
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, New York|
|Memorial Sloan Kettering|
|New York, New York, United States, 10021|
|Principal Investigator:||Patrick Y. Wen, MD||Dana-Farber Cancer Institute|