'First-in-human' drug for malignant glioma available in experimental trial

February 15, 2012

The UC Cancer Institute is one of three centers internationally approved to test an experimental drug's safety and pharmacokinetics and also assess the clinical benefit against recurrent malignant glioma, an aggressive form of brain cancer.

The "first-in-human" phase-1 trial is expected to enroll up to 60 patients at clinical sites in the United States and Australia.

Led by Olivier Rixe, MD, PhD, this trial uses antibody-drug conjugate (ADC) technology, a new drug delivery concept currently being investigated in the treatment of various cancers. ADC molecules consist of an antibody linked to a specific cytotoxic drug that is intended to target, bind and disperse only in .

The experimental drug (called AMG 595) is intended to target a specific mutated cell receptor (EGFRvIII) which exists on the surface of tumor cells in up to 30 percent of patients with malignant gliomas. Preliminary studies in animals have shown that ADC molecules can effectively find these specific cancer cells, then enter them and release an active cytotoxic agent with the aim of killing the while minimizing damage to the surrounding normal tissue.

"This allows us to use a highly cytotoxic drug targeted to the cancer cells in the brain based on a specific cellular marker," explains Rixe, John and Gladys Strauss Chair in Cancer Research at the UC College of Medicine and director of the /Phase 1 Clinical Trials Program. "Until recently, patients have traditionally been excluded from phase-1 oncology studies, so finding drugs to effectively target and make real advances against this particular type of very has been virtually impossible."

Patients who have failed first- and second-line therapies for may qualify to participate in this trial. Potential candidates will be screened for the EGFRvIII mutation using tumor samples obtained during their original surgery prior to enrollment.

Each patient's response to the treatment and overall health will be clinically monitored through blood, urine and imaging tests at regular intervals through the trial. Patients may be involved in the study for about eight months, including a pre-study assessment period and safety follow-up visit.

This is a paradigm shift in the way we look at gliomas, because the ADC model has the potential to revolutionize the way we deliver chemotherapy to while sparing the surrounding healthy tissue." adds Rixe.

"Our goal is to improve the benefits-risk ratio of treatment by increasing anti-tumor activity while reducing the side effects of toxicity on healthy tissue."

The clinical trial of AMG 595, the experimental drug being used in the study, is sponsored by Amgen, a biotechnology company based in Thousand Oaks, California.

More than 22,000 people in the United States are diagnosed with a primary malignant brain tumor every year, according to the National Cancer Institute, and the majority of these are malignant gliomas which have a poor prognosis.

In 2011, the UC Cancer Institute partnered with the UC Neuroscience Institute's Brain Tumor Center to launch a translational research program aimed at understanding the biological mechanisms of cancer's spread to the brain and developing more effective ways to treat the condition.

Both programs are part of the Cincinnati Cancer Center, a joint cancer program involving the UC College of Medicine, Cincinnati Children's Hospital Medical Center and UC Health. The collaborative initiative brings together interdisciplinary research teams of caring scientists and health professionals to research and develop new cures, while providing a continuum of care for children, adults and families with cancer.

Explore further: Novel brain tumor vaccine acts like bloodhound to locate cancer cells

Related Stories

Novel brain tumor vaccine acts like bloodhound to locate cancer cells

January 5, 2012
A national clinical trial testing the efficacy of a novel brain tumor vaccine has begun at Wake Forest Baptist Medical Center, the only facility in the Southeast to participate.

Recommended for you

What does hair loss have to teach us about cancer metastasis?

December 15, 2017
Understanding how cancer cells are able to metastasize—migrate from the primary tumor to distant sites in the body—and developing therapies to inhibit this process are the focus of many laboratories around the country. ...

Cancer immunotherapy may work better in patients with specific genes

December 15, 2017
Cancer cells arise when DNA is mutated, and these cells should be recognized as "foreign" by the immune system. However, cancer cells have found ways to evade detection by the immune system.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

December 15, 2017
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

Scientists unlock structure of mTOR, a key cancer cell signaling protein

December 14, 2017
Researchers in the Sloan Kettering Institute have solved the structure of an important signaling molecule in cancer cells. They used a new technology called cryo-EM to visualize the structure in three dimensions. The detailed ...

'Bet hedging' explains the efficacy of many combination cancer therapies

December 14, 2017
The efficacy of many FDA-approved cancer drug combinations is not due to synergistic interactions between drugs, but rather to a form of "bet hedging," according to a new study published by Harvard Medical School researchers ...

Liquid biopsy results differed substantially between two providers

December 14, 2017
Two Johns Hopkins prostate cancer researchers found significant disparities when they submitted identical patient samples to two different commercial liquid biopsy providers. Liquid biopsy is a new and noninvasive alternative ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.