MK-2206 for Recurrent Malignant Glioma

NCT01249105 | Withdrawn Phase 2 DMC

• 2 other identifiers: 10-160018-00
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Malignant Glioma

Keywords

MK-2206; GBM

Outcome Measures

Primary Outcomes (3)

• Part 1: Akt inhibition

  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.

  2 years

• Part 1: MK-2206 levels in tumor tissue

  The level of MK-2206 in tumor tissue.

  2 years

• Part 2: Therapeutic efficacy

  Determine the therapeutic efficacy of MK-2206 as measured by progression-free survival at 6 months.

  3 years

Study Arms (2)

Part 1

EXPERIMENTAL

Patients with recurrent glioblastoma multiforme (GBM) who require reoperation.

Drug: MK-2206

Part 2

EXPERIMENTAL

Participants with GBM and with anaplastic glioma

Drug: MK-2206

Interventions

MK-2206 DRUG

Taken orally once a week

Part 1; Part 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed glioblastoma or gliosarcoma. Participants will be eligible if the orginal histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or gliosarcoma is made.
• Unequivocal evidence for tumor progression by MRI or CT scan. A scan should be performed within 14 days of registration. The same type of scan must be used throughout the period of protocol treatment for tumor measurement. MRI scans are preferred whenever possible. If participants in Part 2 of the study are taking corticosteroids, the dose must be stable or decreasing for at least 5 days prior to the scan.
• Must have recovered from the toxic effects of prior therapy. From the start of scheduled study treatment, the following time periods must have elapsed: 4 weeks from any investigational agent, 4 weeks from cytotoxic therapy, or 4 weeks from other anti-tumor therapies.
• Must have failed prior radiation therapy and must have an interval of at least 12 weeks from the completion of radiation therapy.
• Prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of progressive disease based upon nuclear imaging, MR spectroscopy, or histopathology.
• Participants having undergone recent resection of recurrent or progressive tumor will be eligible as long as the following conditions apply: a) they have recovered from the effects of surgery, b) residual disease following resection of recurrent tumor is not mandated for eligibility. To best assess the extent of residual disease post-operatively, and MRI or CT scan should be done no later than 96 hours following surgery or at least 4 weeks post-operatively, in either case within 14 days prior to registration. If participants in Part 2 of the study are taking corticosteroids, the dose must be stable or decreasing for at least 5 days prior to the scan. If steroids are added or the steroid dose is increased between the date of the screening MRI or CT scan and the start of treatment, a new baseline MRI or CT is required.
• years of age or older
• Life expectancy of \> 8 weeks
• Karnofsky performance status 60 or greater
• Normal organ and marrow function as outlined in the protocol
• At least 35-45 paraffin slides (standard thickness of 4 microns) from any prior surgery available for correlative studies
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
• Participants must be registered for the Ivy Consortium Tissue and Data Study.
• Additional Part 1 Eligibility Criteria:
• Must be deemed by the site Investigator to be an appropriate candidate for surgical resection.

You may not qualify if:

• Participants who have received therapy for more than two prior relapses
• Prior treatment with Akt inhibitors, PI3K inhibitors, mTOR inhibitors, or anti-angiogenic agents
• Must not be on an enzyme-inducing anti-epileptic drug. If previously on an EIAED, the patient must be off of it for at least two weeks prior to registration.
• Receiving any medications or substances that are strong inhibitors or inducers of CYP3A4
• Receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206
• History or current evidence of heart disease
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, chronic liver disease, chronic renal disease, chronic pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements.
• Poorly controlled diabetes mellitus
• Pregnant or breastfeeding women
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell squamous cell carcinoma of the skin
• HIV-positive individuals

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Massachusetts General Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator
• University of California, Los Angeles: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Glioma

Interventions

MK 2206

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Patrick Y. Wen, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 24, 2010
• First Posted: November 29, 2010
• Last Updated: March 10, 2016

Record last verified: 2016-03

Locations

US (5)