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Therapy for Recurrent Glioblastoma Multiforme (GBM) Shows Promise in Clinical Trial


Inclusionary Criteria

Patients must be at least 18 years of age
Histopathologic documentation of GBM at initial diagnosis
Clinical and/or radiographic evidence of first recurrent or progressive supratentorial tumor
Initial treatment includes surgery/biopsy and radiation therapy completed > 4 weeks prior to study entry
Recovery from toxicity of prior therapy.
Minimum intervals required prior to study entry:
> 6 weeks after receiving nitrosourea cytotoxic drug
> 4 weeks after receiving any non-nitrosourea cytotoxic drug or any systemic investigational agent
> 2 weeks after receiving any non-cytotoxic anti-tumor drug
For more information, call Carol Macpherson at (773) 250-0423.

A number of the world’s leading brain tumor treatment centers are investigating a new tumor-targeting platform and rapid drug delivery system designed to treat recurrent glioblastoma multiforme (GBM), a deadly form of brain cancer with few current treatment options.

Each year 10,000 Americans are diagnosed with glioblastoma multiforme. The median survival time after initial detection is 12 months and 6 months after recurrence. The usual treatment is surgery, followed by radiation and anti-cancer chemicals. But unlike solid-mass tumors, glioblastomas have tiny tentacles that spread into the brain, making it impossible for a surgeon to remove every bit of the tumor. The tumor grows back, usually within six months, and is, for the most part, unresponsive to current drugs.(i)

The GLIADEL® Wafer, which delivers BCNU (or carmustine, a commonly used chemotherapeutic anti-cancer agent) directly to the brain tumor resection cavity, is one of the available therapies for GBM. Up to eight dime-sized wafers are placed in the space once occupied by the tumor at the time of resection. The wafers slowly dissolve over the next two to three weeks, bathing the cells with BCNU. The GLIADEL® Wafer has been approved by the Food and Drug Administration (FDA) for the treatment of recurrent and newly diagnosed GBM. Studies have shown that GLIADEL® Wafer extends the median survival by eight weeks.(ii)

The PRECISE trial is a Phase III clinical trial of NeoPharm’s investigational drug IL13-PE38QQR (cintredekin besudotox). The purpose of the randomized trial is to compare the survival of patients with first recurrent GBM treated with IL13-PE38QQR, with the survival of patients treated with GLIADEL® Wafer following surgical tumor resection. Safety and quality of life are also assessed in the study.(iii)

IL13-PE38QQR is made from a human protein, Interleukin 13 (IL-13), linked to a bacterial toxin, Pseudomonas exotoxin (PE). Interleukin instructs immune cells to divide or differentiate. IL-13 receptors are found on malignant gliomas cells, but not to any measurable degree, if at all, on healthy brain cells. IL13-PE38QQR is designed to bind to IL-13 receptors on the tumor like a key fitting into a lock. The cancer cell latches onto and absorbs the IL-13 and the attached toxic agent, PE38QQR. As a result, the cancer cell dies. The toxin is harmless to healthy cells, which lack IL-13 receptors.(iv)

Because IL13-PE38QQR molecules are too large to pass through the blood brain barrier, the study drug is infused directly into the brain tissue surrounding the tumor resection cavity using convection-enhanced delivery (CED). This method of treatment involves surgical implantation of 2-4 catheters in the brain. Pumps are used to infuse the drug solution slowly into the area surrounding the tumor resection cavity for a period of 96 hours (four days).

“The early studies look promising for IL13-PE38QQR, but the study drug may not work for everyone,” says Dr. Leonard Cerullo, neurosurgeon and founding member of Chicago Institute of Neurosurgery and Neuroresearch (CINN), one of the participating trial sites. “When it works, it can be very effective.”

Phase I results for IL13-PE38QQR look promising. The median survival rate for 45 patients with GBM receiving IL13-PE38QQR almost doubled from 26 weeks to 44 weeks. Several patients survived for more than three years including a few without any additional anti-tumor treatment after IL13-PE38QQR, and the FDA has granted IL13-PE38QQR rare fast-track designation to accelerate approval.(v)

More than 40 prestigious medical centers worldwide are participating in the PRECISE trial, including Memorial Sloan Kettering Cancer Center, Cleveland Clinic, M.D. Anderson Cancer Center, and CINN at Rush University Medical Center. Given the advancing PRECISE Phase III study and the encouraging results of the Phase I studies, a Phase II study for patients with new diagnosis of GBM including IL13-PE38QQR, radiation therapy and temozolomide (Temodar®) is planned for 2006.

i Mary Ellen Egan, “Brain Tumors, Taking On a Monster,” Forbes (November 15, 2004)

ii Gliadel Wafer Product Insert, Guilford Pharmaceuticals, Inc., March 2003

http://www.mgipharma.com/pdfs/gliadel_pi.pdf

iii Precise Trial, “About Precise Trial,” Available: March 8, 2004. http://www.precisetrial.com/index.php?section=4.

iv Ibid.

v Ibid.