IRB Number:

07-006312

Trial Status:

Open for Enrollment

Phase: II

Why is this study being done?

The purpose of this research study is to:
- Add the study drug everolimus to the standard treatment of temozolomide and radiation to see if this addition makes the standard treatment better. Everolimus helps to stop signals that cause tumors to grow. Everolimus is an investigational drug and is currently not approved for use in brain tumors.
- Test the safety of the everolimus when given in combination with temozolomide.
- Find the highest safe dose of everolimus in combination with temozolomide after radiation is complete that can safely be given without causing bad side effects.
- See what effects (good and bad) it has on patients and their cancer.
- Test whether changes on a research FDG PET/CT or FDG PET scan can predict a response to everolimus therapy. FDG is a radioactive chemical that is injected into a patient's vein before the scan and is an imaging agent routinely used throughout the country.

Who is Eligible to Participate in the Study?

-Age 18 or older
-Diagnosed with Glioblastoma Multiforme (GBM, grade 4 astrocytoma). Gliosarcomas and other grade 4 astrocytoma variants (e.g. giant cell) may be included. Grade 4 oligodendrogliomas or oligoastrocytomas are specifically excluded.
-No prior chemotherapy received
-No prior radiation to the brain received

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

If agreeing to be in the study, patients will be asked to participate in the following:

During this study, patients will take everolimus tablets and temozolomide capsules. Because temozolomide can sometimes cause an upset stomach, doctors will give patients an anti-nausea pill to take in combination with their temozolomide. A diary that tracks when patients take the study drugs will need to be filled out every day while they are taking temozolomide and everolimus. The combination of everolimus with temozolomide can put patients at a higher risk of serious infections. As a result, patients will be required to take antibiotics while on this study to reduce the risk of these infections.

Before enrolling in this study, patients will have had a general physical exam, neurologic exam, routine blood tests, pregnancy test (if applicable) within seven days prior to registration, and MRI or CT of the head. Once treatment starts, patients will have blood tests and visit their doctor before each cycle (every 28 days) of temozolomide. After patients complete all treatment, they will be followed with the same tests (excluding the pregnancy test) as mentioned previously; every two months in the first year, then every three months in year two, then every six months until five years from the completion of treatment. Brain tumor tissue collected previously during a patient's surgery will also be reviewed to confirm the results of the patient's local laboratory review. This is mandatory in order to participate in this study.

Before beginning the study:
Patients will need to have the following exams, tests, or procedures to find out if they can participate in the study. These exams, tests, or procedures are part of regular cancer care and may be completed even if they do not join the study. If patients have had some of them recently, they may not need to be repeated. This will be up to the study doctor.

- Routine blood tests
- Neurological and physical exams
- MRI or CT of the brain
- Pregnancy test (if applicable) within seven days prior to registration

During the study:
If the exams, tests, and procedures show that patients can participate in the study, and they choose to take part, patients will need the following tests and procedures. They are part of regular cancer care. Additionally, patients would undergo FDG PET/CT or FDG PET scans both before starting everolimus and after their second dose of everolimus.

- Routine blood tests
- Neurological and physical exams
- MRI or CT of the brain

Cycle 1
Everolimus is taken once per week for two weeks. Before patients start taking everolimus, they will have a research FDG PET/CT or FDG PET scan of their brain. Patients will then start taking everolimus once per week. After their second dose of everolimus, they will have another research FDG PET/CT or FDG PET scan. Then, patients will begin radiation treatments (radiation treatments must begin sometime after second dose of everolimus on Day 8 but before the third dose of everolimus on Day 15). Patients will start taking temozolomide daily starting with the first day of radiation treatments. Patients will get radiation treatments five days a week for six weeks. During the six weeks of radiation, patients will continue taking everolimus once per week and will also take temozolomide daily. The FDG PET/CT or FDG PET scans will be completed in the Division of Nuclear Medicine. For each FDG PET/CT or FDG PET scan, patients will have a very small amount of radioactive chemical injected into their veins and then their tumors will be scanned one hour later. Participants at Mayo Clinic Rochester who will undergo the PET/CT scan will also be exposed to X-ray radiation (CT scan) during the procedure.

Cycle 2
After completion of the radiation therapy, patients will have a 4-6 week rest period. This rest period will be considered cycle 2. At the end of cycle 2 patients will be examined to see how they are doing.

Cycles 3-8
For cycles 3-8, each cycle is 28 days long. During each cycle, patients will take everolimus once per week. Patients will take temozolomide for the first five days of the first week of each cycle.

Cycles 9+
If after cycle 8, a patient and their doctor decide the patient should continue treatment, the patient will take only everolimus once per week. The patient will keep taking everolimus, until the patient or the doctor decide the patient should not keep taking everolimus.

While taking everolimus:
Patients will need these tests and procedure done regularly:
- Routine blood tests
- Neurological and physical exams
- MRI or CT of the brain

The drug (everolimus) used in this study is considered investigational, which means it has either not been approved by the U. S. Food and Drug Administration (FDA) for routine clinical use or for the use described in this study. However, the FDA has allowed the use of this drug in this research study.

Mandatory Research Laboratory Tests:
This study also has mandatory research laboratory tests that will be performed to study small samples of patient's blood and tissue.

Mayo Clinic Rochester and Jacksonville: Blood samples will be done by drawing blood from a vein. The blood will be taken at week 1 of cycle 1 (approximately ½ teaspoon of the blood will be taken one day after the first dose of everolimus) and week 2 of cycle 1 (approximately ½ teaspoon of the blood will be taken just before the second dose of everolimus (7 days after the first dose). The blood samples will be sent to laboratories associated with Novartis Pharmaceuticals, which is providing the study drug everolimus.

Mayo Clinic Rochester and Jacksonville: Tissue samples collected previously during a patient's surgery will be sent to laboratories associated with the North Central
Cancer Treatment Group for testing. These tests will be completed to understand how the patient's cancer responds to treatment. It is hoped that this will help investigators better understand this type of cancer. The results of these tests will not be sent to the patient or the study doctor and will not be used in planning patient's care. These tests are for research purposes only and the patient will not have to pay for them. A patient cannot take part in this study without taking part in these research laboratory tests.

How long will the Study run?

Patients will be in the study as long as their disease does not get worse, or until they have side effects that are unacceptable. How long patients are in the study will depend on how they do with this drug and how their cancer acts. Even if patients stop taking the study drug, the research staff will want to stay in contact with patients.

Sponsor(s): North Central Cancer Treatment Group (NCCTG)

Study Activation/Registration Date: 05/22/2008

IRB Review and Approval Date: 04/24/2008

Study Type: Treatment

Projected Accrual: The plan is to enroll up to 117 patients to participate from multiple medical centers.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Jann N. Sarkaria, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623, or e-mail cancerclinicaltrials@mayo.edu


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Rochester, MN
• Jacksonville, FL

Last updated: 11/17/2008