First Patient Enrolled in the World’s Largest Brain Cancer Clinical Trial

Glioblastoma with extreme nuclear enlargement.
Glioblastoma with extreme nuclear enlargement.

Glioblastoma, also called GBM, is one of the deadliest cancers with only a few effective available therapies. When treated with surgery, radiation and chemotherapy, patients have a median life expectancy of 11 to 15 months. The disease most commonly affects men ages 60 or older, although it can develop at any age in both men and women. While gilioblastoma is generally found in the cerebral hemispheres of the brain, the disease can also be found in other parts of the brain. But the disease rarely spread outside the brain.

The National Cancer Institute (NCI) estimates that 22,850 adults were diagnosed with brain and other nervous system cancers in 2015. It also estimates that in the same year, more than 15,000 of those diagnoses resulted in death. The disease represent about 15% of all primary brain tumors. Glioblastomas are slightly more common in men than in women.

Treatment
Glioblastoma can be difficult to treat. While some cells may respond well to certain therapies, others may not be affected at all. To advance treatment benefits, a treatment plan for glioblastoma may therefore combine several approaches.

Beyond the available treatment, scientists have learned much about the molecular characteristics of glioblastoma. However, this knowledge has not yet been translated into clinical improvements for patients. At the same time, novel therapies being developed require answers related to safety and efficacy.

Novel trial concept
Earlier this week the Henry Ford Cancer Institute enrolled a first patient in the GBM Adaptive Global Innovative Learning Environment (GBM AGILE) – a novel, multi-arm, platform trial design and architecture made possible by an international collaboration of experts in the care of patients with glioblastoma and the design of clinical trials.[1]

Led by the trial sponsor Global Coalition for Adaptive Research (GCAR), GBM AGILE is a seamless Phase II (Efficacy and Safety) / Phase III (Confirmatory) trial aimed at identifying the most effective therapies for patients with glioblastoma, the most aggressive form of brain cancer.

Designed as a next-generation clinical trial program and the first-ever adaptive platform trial for the treatment of patients with brain cancer, the GBM AGILE trial is a move away from the traditional, one-size-fits-all approach to clinical trials. It is a major step forward for Precision Medicine.[1]

“We are launching an era of unprecedented collaboration and advancement in glioblastoma treatment,” said Steven Kalkanis, MD, chairman of the Department of Neurosurgery at Henry Ford Health System and medical director of the Henry Ford Cancer Institute.

“Current treatments have been refined – including surgery, radiation and chemotherapy – but in the era of molecular medicine, dramatic leaps in outcomes through immunotherapy or targeted therapies are yet to be fully realized. With GBM AGILE, those dramatic leaps in outcomes will be more attainable, and at a faster pace, than ever before,” Kalkanis added.

Traditional trials
Traditional clinical trials take three-to-seven years to produce results,  The studies cannot be modified once started, and often only investigate one specific treatment against the available standard of care, or, in some cases, best supportive care.

The GBM AGILE study is uniquely designed as a long-standing platform with the ability to test multiple therapies concurrently against a common control or the current standard of care. This approach enables more participating patients – and more patients to have access to experimental, investigational therapies.

Another innovation of GBM AGILE trial is adaptive randomization, which means that the trial is continuously updated with the latest information. As information accrues, the trial defines subsets of patients more likely to benefit from therapy. Patients are more likely to receive promising therapies at a faster and less costly rate.

“Progress in the treatment of patients with malignant brain tumors has been slow,” said Tom Mikkelsen, M.D. of the Henry Ford Cancer Institute and medical director of the Precision Medicine Program and Clinical Trials Office at Henry Ford Health System.

“The efficiency, speed and learning of GBM AGILE is intended to allow rapid discovery of better and better treatments for patients with glioblastoma. The era of data-driven innovation has arrived, and it’s being applied to the most difficult problems in cancer therapy,” Mikkelsen concluded.

Delaware Attorney General Beau Biden at a Justice Department press conferences (May 21, 2013). On May 30, 2015, Biden, died at age 46 after having battled brain cancer for several years. In a statement, his father, Vice President’s Joe Biden’s office commented: “The entire Biden family is saddened beyond words.” The nature and seriousness of the illness had not been previously disclosed to the public, and the Vice President had quietly reduced his public schedule in order to spend more time with his son. At the time of his death, Beau Biden had been widely seen as the front-runner to be the Democratic nominee for Governor of Delaware in 2016.

GBM Knowledge Network
GBM AGILE was first conceived in 2015 by an international group of more than 130 clinicians, researchers, biostatisticians, imagers, pathologists, patient advocates, and leaders from government and industry known as the “GBM Knowledge Network.” It came together in response to a worldwide effort known as The Cancer Genome Atlas (TCGA), which was launched in 2006 by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI).

The participating organizations led a nationally-coordinated effort to perform a 10-year, deep-dive into the molecular basis of certain kinds of cancers. One of the first types of tumors studied in the landmark precision medicine effort was glioblastoma. Henry Ford was a major TCGA contributor, nearly 25% of all the gliomas studied over the course of the initiative having been donated by Henry Ford’s Hermelin Brain Tumor Center.

Beau Biden
Former Vice President Joe Biden has been an outspoken supporter of GBM AGILE study and attended the GBM AGILE launch event in November 2015. Biden’s son, Beau Biden, passed away from glioblastoma in May 2015 at the age of 46. Beau had been diagnosed in 2013 and was treated with surgery, chemotherapy, and radiation. He suffered a recurrence in the spring of 2015, at which time his condition deteriorated rapidly. Biden acknowledged the potential of GBM AGILE study to offer unparalleled hope for many patients who had previously waited several years to benefit from advances in brain cancer research.

Open exchange of ideas
Henry Ford enrolled GBM AGILE’s first patient in collaboration with GCAR, an international partnership that comprises some of the world’s foremost clinical, translational, and basic science investigators. Through this collaboration and open exchange of ideas, the ultimate beneficiary—the patient—is supported in the fight against rare and deadly diseases.

“This is an important milestone for GBM AGILE and all those involved in this effort, most importantly, the patients, who desperately need new treatment options. We value the dedication of Tom Mikkelsen and the team at Henry Ford Cancer Institute to make this trial available to their patients and are eager to continue to work with our other committed study sites and investigators to make this trial available to patients across the United States this year, and internationally in 2020,” noted Meredith Buxton, Ph.D, Chief Operating Officer of GCAR, who was also involved in the I-SPY 2 trial, a standing trial platform designed to rapidly screen and evaluate several investigational agents across multiple tumor types prior to moving them to phase III studies.

Reference
[1] Alexander BM, Ba S, Berger MS, Berry DA, Cavenee WK, Chang SM, Cloughesy TF, Jiang T et al. Adaptive Global Innovative Learning Environment for Glioblastoma: GBM AGILE. Clin Cancer Res. 2018 Feb 15;24(4):737-743. doi: 10.1158/1078-0432.CCR-17-0764. Epub 2017 Aug 16.