Phase II clinical trial of Avastin and Tarceva in patients with glioblastoma multiforme

Patients suffering from recently diagnosed malignant brain tumors called glioblastoma multiforme or a rare variant called gliosarcoma may be eligible to participate in a Phase II clinical trial at Cedars-Sinai Medical Center that combines two innovative drugs.

Cedars-Sinai's Cochran Brain Tumor Center is the only site in California and one of only 13 in the nation offering this experimental therapy through the Brain Tumor Trials Collaborative (BTTC) based at M.D. Anderson Cancer Center in Houston.

Glioblastoma multiforme is a highly aggressive, treatment-resistant brain tumor. Even with standard therapies - surgery, chemotherapy and radiation - patient survival averages less than 15 months.

The two anticancer drugs, Avastin® (bevacizumab) and Tarceva® (erlotinib), work through different molecular mechanisms to attack brain tumors. Avastin inhibits vascular endothelial growth factor (VEGF), a protein that contributes to the formation of blood vessels that tumors need for growth. Tarceva is designed to prevent tumor growth by blocking a signal pathway that controls cell division by binding to a cancer cell membrane receptor called epidermal growth factor (EGFR).

Although single-agent targeted therapies have not produced significant improvements in treating glioblastomas, laboratory experiments and studies in animals suggest that a combination approach may have greater impact. This two-drug combination is also in clinical trials for the treatment of other cancers, including non-small cell lung cancer and renal cell carcinoma.

While all glioblastoma multiforme tumors share certain characteristics, they are not all genetically alike. This patient trial is specifically designed for those whose tumor cells have "unmethylated MGMT promoter." This provides an especially strong study of the effects of the new two-drug approach because these tumors are resistant to the type of chemotherapy typically prescribed for patients with glioblastoma.

"Unmethylated MGMT promoter" means that a gene involved in repairing damaged tumor DNA is highly active in the tumor cells. When this gene, MGMT (O6-methylguanine-DNA methyltransferase), is functioning in cancer cells, it makes the tumor resistant to certain types of chemotherapy - including temozolamide, which is often used to treat glioblastoma - because it helps repair the damage the drug inflicts. On the other hand, if the gene is "silenced" (blocked) - through a process called methylation - the tumor will be more vulnerable to temozolomide.

The two-drug therapy will be administered after standard treatment with temozolomide and radiation therapy. Because radiation has been found to increase activation of certain molecular factors that the two drugs target, it is theorized that radiation therapy may stimulate a greater antitumor effect from the drugs.

Source:

Cedars-Sinai Medical Center

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