Malignant GliomaPhase 2NCT01249105
MK-2206 for Recurrent Malignant Glioma
A Phase 2 study testing MK-2206 in people with Malignant Glioma, run by Dana-Farber Cancer Institute at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma
- What is being tested?
- MK-2206
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 5 sitesUnited States
- Study dates
- Start not givento not given
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 18 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.
- Must have frozen tumor sample (minimum of 100mg of tissue) from any prior surgery available for correlative studies
- Unequivocal evidence for tumor progression by MRI or CT scan. For this scan only, increasing corticosteroid doses are acceptable.
- Additional Part 2 Eligibility Criteria:
- Subjects with anaplastic gliomas who meet other eligibility criteria are eligible.
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
UCLA Medical Center
Los Angeles, California, 90095
Memorial Sloan Kettering
New York, New York, 10021
About this study
Official title: A Phase II Study of 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.
Read the detailed description
- 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.
- Conditions
- Malignant Glioma
- Being tested
- MK-2206
- Keywords
- MK-2206, GBM
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-2206Drug
Taken orally once a week
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | Patients with recurrent glioblastoma multiforme (GBM) who require reoperation. Receives: Drug: MK-2206 |
| Part 2 | Experimental | Participants with GBM and with anaplastic glioma Receives: Drug: MK-2206 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Part 1: MK-2206 levels in tumor tissue
The level of MK-2206 in tumor tissue.
Measured: 2 years
Part 2: Therapeutic efficacy
Determine the therapeutic efficacy of MK-2206 as measured by progression-free survival at 6 months.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2010 (estimated)
Why it stopped: Merck (supplier of study drug \& funding) has undergone a large reprioritization, in which they had to terminate many oncology trials, including this one.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant GliomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Memorial Sloan Kettering Cancer Center, University of California, Los Angeles, Merck Sharp & Dohme LLC
- Investigators
- Patrick Y. Wen, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01249105
- Sponsor's protocol ID
- 10-160
- Other IDs
- 018-00
- Status last verified
- Mar 2016
- First submitted
- 24 Nov 2010
- Last updated
- 10 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of MK-2206 for Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT01249105
- Acronym / sponsor ID
- 10-160
- Conditions
- Malignant Glioma
- Keywords
- MK-2206, GBM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Merck (supplier of study drug \& funding) has undergone a large reprioritization, in which they had to terminate many oncology trials, including this one.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Memorial Sloan Kettering Cancer Center, University of California, Los Angeles, Merck Sharp & Dohme LLC
- First posted
- 29 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: MK-2206Patients with recurrent glioblastoma multiforme (GBM) who require reoperation. |
| Part 2 | Experimental | Drug: MK-2206Participants with GBM and with anaplastic glioma |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-2206Taken orally once a week | Drug | Part 1, Part 2 |
Primary outcome
Part 1: Akt inhibition
Time frame: 2 years
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
The level of MK-2206 in tumor tissue.
Part 2: Therapeutic efficacy
Time frame: 3 years
Determine the therapeutic efficacy of MK-2206 as measured by progression-free survival at 6 months.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Y. Wen, MD principal investigator
Dana-Farber Cancer Institute
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MK-2206 in people with Malignant Glioma, run by Dana-Farber Cancer Institute at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 10 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Akt inhibition (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2016.