Investigating New Treatments for Patients with Glioblastoma Multiforme
With funding from the National Cancer Institute, principal investigator Jay-Jiguang Zhu, M.D., Ph.D., is leading a phase II/ III clinical trial studying the efficacy of veliparib with temozolomide compared to temolozomide alone in treating patients with glioblastoma multiforme (GBM) or gliosarcoma. The trial is currently enrolling patients at the Memorial Hermann Mischer Neuroscience Institute at the Texas Medical Center and McGovern Medical School at UTHealth.
“Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by interfering with DNA replication of the cells, by stopping them from dividing or by stopping them from spreading,” says Dr. Zhu, director of neuro-oncology at the Mischer Neuroscience Institute and an associate professor in the Vivian L. Smith Department of Neurosurgery at the McGovern Medical School. “Veliparib, a poly(ADP-ribose) polymerase (PARP) -1 and -2 inhibitor, may stop the growth of tumor cells by blocking some of the DNA repair enzymes needed for cell growth and survival. We want to know if temozolomide is more effective with veliparib in treating glioblastoma multiforme.”
More than 400 patients will be enrolled in the eight-year study at sites located around the country. The trial, “A Phase II/III Randomized Trial of Veliparib or Placebo in Combination with Adjuvant Temozolomide in Newly Diagnosed Glioblastoma with O-6-methylguanineDNA methyltransferase (MGMT) Promoter Hypermethylation,” will run through June 2022.
Researching Cures for Other Cancers
Dr. Zhu is principal investigator in several other trials that give eligible study participants access to new and advanced treatments. Memorial Hermann-TMC is the only Houston site for a study of 4-Demethyl-4cholesteryloxycarbonylpenclome (DM-CHOC-PEN) in patients with brain tumors. DM-CHOC-PEN is a polychlorinated pyridine cholesteryl carbonate, which exerts antineoplastic activity through cross-linking DNA strands in patients with brain tumors.
“During a phase I study, DM-CHOCPEN demonstrated the capability of high CNS penetration to inhibit or halt the development of tumors in patients with advanced cancers, including melanoma, lung cancer and breast cancer involving the central nervous system, and glioblastoma multiforme,” says Dr. Zhu, who is fellowship trained at Massachusetts General Hospital and focuses his practice on primary brain tumors and primary central nervous system (CNS) lymphomas, as well as brain metastases and leptomeningeal spread of systemic malignancies. “These findings support the preclinical responses seen in mice, and no hematological, renal or cardiovascular toxicities or cognitive impairment was noted in the phase I human trial or in previous preclinical studies.” The trial is open to patients with advanced lung, breast and melanoma cancers that have spread to the central nervous system as well as those with primary CNS malignancies. The expected study completion date is August 2016.
Two other trials led by Dr. Zhu are ongoing but not currently enrolling participants. A phase III multicenter, randomized, controlled trial is testing the efficacy and safety of a medical device called Novo TTF-100A for newly diagnosed GBM patients in combination with temozolomide, compared to temozolomide alone. The device, which patients wear on their scalp, provides a constant, safe, low-voltage electric field that has been shown to reduce tumor cell survival and division capacity.
The device was approved by the FDA for progressive GBM in April 2011. The interim analysis of the trial data showed significant improvement of progression survival time and overall survival duration in participants randomized to the treatment arm of the study. Based on this trial result, the FDA approved the device for newly diagnosed GBM in October 2015. The expected study completion date is July 2016.
In addition, he is leading an openlabel phase I/II (safety lead-in) study of trans sodium crocetinate (TSC) with concomitant treatment of fractionated radiation therapy and temozolomide in newly diagnosed GBM patients. The trial examines the safety and efficacy of TSC as a radiation sensitizer for the treatment of malignant tumors. The study is ongoing but not currently recruiting participants.
Dr. Zhu was also principal investigator in a randomized, double-blind, controlled phase IIB clinical trial testing the safety and efficacy of the vaccine ICT-107 for newly diagnosed GBM patients following resection and chemoradiation. The trial, which began enrollment in August 2011 and was completed in December 2015, showed improved, progressive-free survival of patients who are human leukocyte antigen (HLA) A2 positive. HLA genes are key to the activity of the immune system in identifying the body’s own proteins versus proteins of foreign origin. A phase III trial for HLA A2 positive GBM patients has just opened at Memorial Hermann-TMC, and patients are now being enrolled.
Other Neuro Oncology Clinical Trials
Sigmund Hsu, M.D., who is fellowship trained at The University of Texas MD Anderson Cancer Center, is principal investigator in several studies, including in the trial of a novel taxol chemotherapy compound, TPI 287, which crosses the blood-brain barrier and will be administered in combination with bevacizumab, versus bevacizumab alone in adults with recurrent glioblastoma. In addition, he is leading a phase II dose-escalation study of TPI 287 in combination with bevacizumab in adults with recurrent or progressive glioblastoma following a bevacizumab containing regimen.
Dr. Hsu is also the lead physician in the FoundationOne™ Registry study, a prospective observational study to examine practice patterns and impact on clinical decision-making associated with the FoundationOne next-generation sequencing test. The study enables physicians affiliated with the Mischer Neuroscience Institute to recommend optimal personalized treatment for patients with cancer. Patients benefit from other innovative and advanced technologies, including motor and language mapping, functional neuroimaging, frameless stereotactic navigation in surgery and awake craniotomies performed under local anesthesia, as well as minimally invasive procedures, including neuroendoscopy and stereotactic radiosurgery.
Both studies are aligned with Dr. Hsu’s clinical and research interests in the discovery of new and more effective therapies for patients with primary brain tumors, treatment of metastatic cancer to the brain and spinal cord, and the evaluation and treatment of neurological problems in cancer patients.