IRB Number:

07-004371

Trial Status:

Open for Enrollment

Phase: II

Why is this study being done?

Patients are being asked to take part in this research study because they have been diagnosed with glioblastoma multiforme (GBM) and have had surgery to have it removed. Their doctor has also determined that temozolomide, a commonly used chemotherapy for this disease, is an appropriate therapy for the patient. This study will find out whether adding the CDX-110+GM-CSF vaccine to temozolomide is better or worse than temozolomide by itself at preventing brain tumors from growing, and helping patients with brain tumors live longer.

The CDX-110 + GM-CSF vaccine is an experimental (investigational) vaccine that is being tested to treat glioblastoma by activating the immune system to fight the cancer.
An investigational vaccine is one that is not approved by the U.S. Food and Drug Administration (FDA). The purpose of CDX-110 is to "train" the immune system to recognize a protein called EGFRvIII. About half of the glioblastoma tumors contain EGFRvIII, and EGFRvIII has only been found in cancer cells. It is hoped that when CDX-110 is given to a patient with a glioblastoma tumor containing EGFRvIII, the immune system will "recognize" and kill the glioblastoma cells.

GM-CSF is a man-made version of a substance naturally produced by a patient's body that "activates" the immune system. GM-CSF has been approved by the FDA as a treatment to help bone marrow recovery after bone marrow transplants, and to help restore white blood cells after chemotherapy in certain cancer patients. GM-CSF has also been used in many clinical studies, including studies that investigate GM-CSF in combination with different cancer vaccines as an "immune activator". Thus, it is hoped that using GM-CSF with CDX-110 will increase the immune response against tumor cells.
Patients will receive GM-CSF at a dose of 150 micrograms. This dose is significantly lower than the FDA approved dose for bone marrow stimulation (the study dose is about one-third of the FDA-approved dose).

Temozolomide is a chemotherapy drug (capsule that is taken by mouth) that has been approved by the FDA for the treatment of brain cancer. Temozolomide, along with radiation therapy and surgery, is currently the most common treatment, and is generally considered the best available treatment, for this type of brain tumor.

Who is Eligible to Participate in the Study?

- Age 18 or older
- Diagnosed with glioblastoma multiforme (GBM) and have had surgery to have it removed.
- No stereotactic radiosurgery prior to or following surgical resection, or placement of Gliadel® wafers

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

What is Involved With this Study?

Screening Period
Before beginning the study:
If the patient agrees to be in the study, there will be a screening period to make sure they are eligible. This period will occur in the two weeks after they complete radiation and chemotherapy.

During the screening period, patients will be asked to do the following:
- Have a physical examination with vital signs, weight, and height
- Discuss their medical history and any previous treatments or medications (including current medications)
- Have a sample of the patient's brain tumor (saved from their original surgery) sent to a central laboratory to see whether their tumor contains EGFRvIII, to verify their diagnosis of glioblastoma multiforme, and to see whether their tumor contains the "activated" form of an enzyme called MGMT. The purpose of the MGMT test is to evaluate the tumor's ability to repair DNA following chemotherapy.
- Discuss how well they are able to carry out their normal daily activities so they may be scored and their disease status defined;
- Have a pregnancy test if patient is a woman able to become pregnant
- Have a Magnetic Resonance Imaging (MRI) test of their brain to see if their tumor has come back. If this study suggests that their tumor has come back or grown, they will not be eligible to start the study
- Have routine blood and urine tests

If patient's eligibility is confirmed during the screening period, they will enter the treatment period.

Treatment Period
If patients qualify and agree to be in the study, they will have an evaluation to see if they meet the requirements to be included in the study, and then they will be assigned to one of the two treatment groups described below:
- Group 1: CDX-110 vaccine+GM-CSF injections plus maintenance temozolomide (Temodar®) capsules
- Group 2: Control group - maintenance temozolomide (Temodar ®) capsules

A computer program will perform the treatment assignment in a random fashion, much like rolling dice or tossing a coin. For every two patients who will get CDX-10+GMCSF vaccine plus maintenance temozolomide, one patient will get maintenance temozolomide only, so patients have two out of three chances of receiving CDX-110. Neither the patient nor the study doctor will be able to pick which study group the patient is in, but the patient and the study doctor will know which study group they are in.

Treatment cycles will be 28 days long. All patients will receive temozolomide maintenance therapy (TMT) by mouth on days 1-5 of each 28-day cycle.

If a patient is randomly assigned to the CDX-110 vaccine group they will receive three biweekly injections of CDX-110 (mixed with GM-CSF) on Study Days 0, 14, and 28.
This is called the Initiation Period and starts two weeks after the patient finishes chemo-radiation. Seven days after day 28, they will begin the TMT treatment phase. A patient will take temozolomide by mouth on days 1-5 and the CDX-110+GM-CSF vaccine on day 21 of each cycle. Patients will receive up to twelve months of maintenance temozolomide along with monthly CDX-110/GM-CSF injections. CDX-110/GM-CSF injections may continue after patients finish maintenance temozolomide, provided they have no serious side effects and their tumor has not grown.

If patients are randomly assigned to the Control group, cycle 1 will begin five weeks after completing chemo-radiation. They will take a temozolomide capsule once a day on the first five days of each cycle for up to twelve months.

If the doctor determines that the patient's tumor has grown at any time during the study, or if they have serious side effects, the patient will stop study treatments. The patient and their doctor will decide what future treatment, if any, is right for the patient and they may receive alternate treatments at that time. Even after a patient discontinues the study treatment and starts alternative treatment, as part of the study, their doctor and or study staff will still contact the patient every three months for up to two years to see how they are feeling.

During study participation, the following tests may be done:
- Physical exams
- Blood and urine tests
- MRI(s) of brain

How long will the Study run?

Patients will be in the study for up to a maximum of two years or until they cannot tolerate the vaccine. Beyond that, the study staff and sponsor would like to follow the patient's progress for the rest of their life.

Sponsor(s): CellDex Therapeutics, Inc.

Study Activation/Registration Date: 10/25/2007

IRB Review and Approval Date: 09/14/2007

Study Type: Treatment

Projected Accrual: The plan is to have up to 375 patients 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: Kent C. New, 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?

• Jacksonville, FL

Last updated: 05/08/2008