State-Of-The -Art Therapy for Glioblastoma Multiforme

This article was written by Dr. Henry Friedman. Henry S. Friedman, MD, is an internationally recognized neuro-oncologist with a career-long interest in the treatment of children and adults with brain and spinal cord tumors. He has written hundreds of articles on both the clinical and laboratory investigation of these neoplasms.

Grade IV Glio Shrinking

Patients account of recent Avastin success after tumor recurrence.

Blog Introduction

First of all, you are probably wondering who I am and what I know about the world of brain tumors. I am the child of a father who was diagnosed with a Glioblastoma IV(GBM)
in the spring of 2007. This blog is my best effort at compiling the type of info that I was searching for when all of a sudden this cancer became part of my life. I'll focus on helping people find information and hope. No statistics or time-lines here! Alstto please feel free to email me with any questions. I can't promise that I can answer everything but I promise that if I don't have the answer I can point you in the right direction.

Celldex Therapeutics Announces Orphan Drug Designation For CDX-110, A Novel EGFRvII Vaccine For Glioblastoma Multiforme

PR Newswire

December 7, 2007

PHILLIPSBURG, N.J. -- Celldex Therapeutics announced today that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for Celldex's CDX-110 for the treatment of EGFRvIII expressing Glioblastoma Multiforme (GBM). GBM is the most common and aggressive form of brain cancer. CDX-110 is an immunotherapy that targets the tumor-specific growth promoter EGFRvIII. Celldex Therapeutics announced a definitive merger agreement with AVANT Immunotherapeutics, Inc. (Nasdaq: AVAN) in October 2007.

In the ACTIVATE phase IIa study, CDX-110 treated GBM patients showed a median survival time of 30 months, more than a 100 percent increase in survival, versus the historical control's median of 14.5 months. The study has demonstrated a median time-to-progression of 13 months (p=0.0001) versus the historical control's median of 6.4 months. An extension study, ACT II, which combines CDX-110 with chemotherapy in a similar patient population, has not yet reached median time-to-progression or survival. However, preliminary progression free survival (PFS) and overall survival (OS) data in ACT II look very similar to the ACTIVATE experience, and the data suggest that chemotherapy and CDX-110 can be administered concurrently while still maintaining strong immune responses.

In September, Celldex randomized its first patient into ACT III, a definitive Phase II/III randomized study of CDX-110 with radiation and temozolomide in patients with newly-diagnosed GBM. The clinical trial is investigating the anticancer activity, impact on survival, and safety of the addition of CDX-110 vaccine to standard of care, versus standard of care alone. Celldex has currently enlisted 18 clinical centers throughout the United States, and also recently received approval from Health Canada to open enrollment in Canada. Furthermore, The National Cancer Institute (NCI) has agreed to collaborate with Celldex in expanded clinical development of CDX-110 under a Clinical Trials Agreement.

"Obtaining orphan designation for CDX-110 is an important milestone for Celldex," said Thomas Davis, M.D., Chief Medical Officer of Celldex Therapeutics. "Approval to expand clinical research into Canada and the scientific and clinical collaboration from the National Cancer Institute all promote our ability to fully explore the promise of CDX-110."

What is Brain Cancer?

In order to define brain cancer we must first understand a little bit about the composition of the brain itself.

The brain is a soft, spongy mass of tissue. It is protected by the bones of the skull and three thin membranes called meninges. Watery fluid called cerebro-spinal fluid cushions the brain. This fluid flows through spaces between the meninges and through spaces within the brain called ventricles.

A network of nerves carries messages back and forth between the brain and the rest of the body. Some nerves go directly from the brain to the eyes, ears, and other parts of the head. Other nerves run through the spinal cord to connect the brain with the other parts of the body. Within the brain and spinal cord, glial cells surround nerve cells and hold them in place.

The brain directs the things we choose to do (like walking and talking) and the things our body does without thinking (like breathing). The brain is also in charge of our senses (sight, hearing, touch, taste, and smell), memory, emotions, and personality.

The three major parts of the brain control different activities:

Cerebrum—The cerebrum is the largest part of the brain. It is at the top of the brain. It uses information from our senses to tell us what is going on around us and tells our body how to respond. It controls reading, thinking, learning, speech, and emotions.

The cerebrum is divided into the left and right cerebral hemispheres, which control separate activities. The right hemisphere controls the muscles on the left side of the body. The left hemisphere controls the muscles on the right side of the body.
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Cerebellum—The cerebellum is under the cerebrum at the back of the brain. The cerebellum controls balance and complex actions like walking and talking.
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Brain Stem—The brain stem connects the brain with the spinal cord. It controls hunger and thirst. It also controls breathing, body temperature, blood pressure, and other basic body functions.

Cancer begins in cells, the building blocks that make up tissues. Tissues make up the organs of the body.

Normally, cells grow and divide to form new cells as the body needs them. When cells grow old, they die, and new cells take their place. Sometimes this orderly process goes wrong. New cells form when the body does not need them, and old cells do not die when they should. These extra cells can form a mass of tissue called a growth or tumor.

Benign and Malignant Brain Tumors

Brain tumors can be benign or malignant:

• Benign brain tumors do not contain cancer cells:

  • Usually, benign tumors can be removed, and they seldom grow back.

  • The border or edge of a benign brain tumor can be clearly seen. Cells from benign tumors do not invade tissues around them or spread to other parts of the body. However, benign tumors can press on sensitive areas of the brain and cause serious health problems.

  • Unlike benign tumors in most other parts of the body, benign brain tumors are sometimes life threatening.

  • Very rarely, a benign brain tumor may become malignant.

• Malignant brain tumors contain cancer cells:

• Malignant brain tumors are generally more serious and often are life threatening.

• They are likely to grow rapidly and crowd or invade the surrounding healthy brain tissue.

• Very rarely, cancer cells may break away from a malignant brain tumor and spread to other parts of the brain, to the spinal cord, or even to other parts of the body. The spread of cancer is called metastasis.

• Sometimes, a malignant tumor does not extend into healthy tissue. The tumor may be contained within a layer of tissue. Or the bones of the skull or another structure in the head may confine it. This kind of tumor is called encapsulated.

Tumor Grade

Doctors sometimes group brain tumors by grade—from low grade (grade I) to high grade (grade IV). The grade of a tumor refers to the way the cells look under a microscope. Cells from high-grade tumors look more abnormal and generally grow faster than cells from low-grade tumors.

Primary Brain Tumors

Tumors that begin in brain tissue are known as primary tumors of the brain. (Information about secondary brain tumors appears in the following section.) Primary brain tumors are named according to the type of cells or the part of the brain in which they begin.

The most common primary brain tumors are gliomas. They begin in glial cells. There are many types of gliomas:

• Astrocytoma—The tumor arises from star-shaped glial cells called astrocytes. In adults, astrocytomas most often arise in the cerebrum. In children, they occur in the brain stem, the cerebrum, and the cerebellum. A grade III astrocytoma is sometimes called an anaplastic astrocytoma. A grade IV astrocytoma is usually called a glioblastoma multiforme.

• Brain stem glioma—The tumor occurs in the lowest part of the brain. Brain stem gliomas most often are diagnosed in young children and middle-aged adults.

• Ependymoma—The tumor arises from cells that line the ventricles or the central canal of the spinal cord. They are most commonly found in children and young adults.

• Oligodendroglioma—This rare tumor arises from cells that make the fatty substance that covers and protects nerves. These tumors usually occur in the cerebrum. They grow slowly and usually do not spread into surrounding brain tissue. They are most common in middle-aged adults.

Some types of brain tumors do not begin in glial cells. The most common of these are:

• Medulloblastoma—This tumor usually arises in the cerebellum. It is the most common brain tumor in children. It is sometimes called a primitive neuroectodermal tumor.

• Meningioma—This tumor arises in the meninges. It usually grows slowly.

• Schwannoma—A tumor that arises from a Schwann cell. These cells line the nerve that controls balance and hearing. This nerve is in the inner ear. The tumor is also called an acoustic neuroma. It occurs most often in adults.

• Craniopharyngioma—The tumor grows at the base of the brain, near the pituitary gland. This type of tumor most often occurs in children.

• Germ cell tumor of the brain—The tumor arises from a germ cell. Most germ cell tumors that arise in the brain occur in people younger than 30. The most common type of germ cell tumor of the brain is a germinoma.

• Pineal region tumor—This rare brain tumor arises in or near the pineal gland. The pineal gland is located between the cerebrum and the cerebellum.

Secondary Brain Tumors

When cancer spreads from its original place to another part of the body, the new tumor has the same kind of abnormal cells and the same name as the primary tumor. Cancer that spreads to the brain from another part of the body is different from a primary brain tumor. When cancer cells spread to the brain from another organ (such as the lung or breast), doctors may call the tumor in the brain a secondary tumor or metastatic tumor. Secondary tumors in the brain are far more common than primary brain tumors.