Clinical Perspectives


Innovative Therapeutic Treatment of Brain Cancer - Phase 0 Clinical Trial “Window of Opportunity”

February 03, 2020

Brain Cancer Drug Delivery Tool

The development of more effective treatments for brain tumors has been hampered by the presence of the blood-brain-barrier (BBB), which keeps most therapeutic drugs from entering into the brain and into brain tumors. While brain tumors often have many of the same biological targets that have led to therapeutic successes in other cancers, most of the drugs that were created to attack those targets are actively excluded from the brain.  Also, brain tumors can be more biologically and genetically diverse than other forms of cancer and hence targeted treatments may show only limited success as cancer cells that do not produce the right target continue to grow unchecked.  In the end, whenever we have a trial of a new drug that fails to show benefit, we are left with very little information that can explain to us why such a promising new therapy did not work.

One way to address these problems is to examine brain tumor tissue that has been treated with a new therapeutic drug to see what impact it is having on the cancer cells. Traditional clinical trials are designed to give a patient an investigational drug and then see whether there is a change on MRI or CT scan, or whether the patient lives longer.  A Phase 0 (“Window of Opportunity”) trial adds another step – give the drug and then sample the tumor tissue (via a clinically indicated craniotomy to remove the tumor) to determine whether the drug reached the tumor and impacted the cancer cells in a way that is likely to lead to tumor shrinkage and/or longer survival.  If the drug is found to have reached the tumor tissue at a concentration that is likely to be effective, and if it is causing changes in the cancer cells that are likely to lead to tumor shrinkage, then there is a strong rationale to move forward into larger clinical trials; otherwise, it is unlikely that the drug will show clinical success and other approaches should be considered.

Michael Vogelbaum, MD, PhD

We are now conducting a clinical trial of a new type of targeted agent being developed by Celgene. This drug, which targets a biological pathway regulating DNA expression in cancer cells, is being given to patients with recurrent glioblastoma (GBM) for four days prior to a planned craniotomy.  The tumor tissue will be analyzed for drug concentration as well as for evidence that the drug has impacted on the cancer cells in a way that would suggest that it is likely to have a benefit in terms of tumor control and prolongation of survival.  Once the patients recover from surgery, they resume the drug and continue it on a regular schedule. 

These types of trials, in which tumor tissue is evaluated during treatment, have been performed routinely in almost all types of cancers except for those in the brain, and they have served as a valuable mechanism to ensure that most patients are treated with investigational drugs that have the highest likelihood for success. “Moffitt Cancer Center has one of the few brain tumor programs that is offering these types of trials to patients and our goal is to make them a more routine part of the development of novel and more effective treatments for our patients,” Dr. Vogelbaum said.

Interested participants should contact a specialist in our Neuro-Oncology Program by completing the online form or contacting a physician liaison for assistance or support. As part of our efforts to shorten referral times as much as possible, online referrals are typically responded to within 24 – 48 hours.