Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Immunotherapy, Pharmaceutical Companies / 22.02.2021

MedicalResearch.com Interview with: https://www.inovio.com/Jeffrey Skolnik, MD Senior Vice President, Clinical Development INOVIO MedicalResearch.com: What is the background for this technology? Would you tell us a little about the brain tumor, Glioblastoma Multiforme? How common is it, whom does it primarily affect?  Response: Glioblastoma (GBM) is the most common malignant brain tumor, affecting more than 10 thousand people each year in the United States. Most people diagnosed with GBM are above the age of 60 years, although GBM can be diagnosed at any age, including in children and young adults. Despite decades of research, GBM remains almost universally fatal. GBM is a tumor of the glial cells of the brain, and current therapies are directed at removing tumor with surgery and killing residual tumor cells with radiation and chemotherapy. More recently, with the introduction of immunotherapies such as immune checkpoint inhibitors (ICI) for the treatment of cancer, clinical studies have tried to add this promising technology to the treatment of GBM. Unfortunately, despite success in other types of cancer, ICIs have not demonstrated any clinical benefit in treating GBM. Newer clinical studies aim at introducing a combination of newer therapies together to try to tackle this terrible disease, and INOVIO’s GBM-001 study is one such example of an innovative approach to treating GBM.    (more…)
Author Interviews, Brain Cancer - Brain Tumors, Imperial College / 20.08.2019

MedicalResearch.com Interview with: Georgios Giamas, (Dr. Biol. Hum.) Professor of Cancer Cell Signalling Director of Research and Knowledge Exchange University of Sussex -School of Life Sciences Visiting Professor, Imperial College, London MedicalResearch.com: What is the background for this study? Response: This study focuses on Glioblastoma (GBM), which is one of the most aggressive solid tumours for which treatment options and biomarkers are limited. MedicalResearch.com: What are the main findings? - Glioblastoma cells produce nanosized vesicles (aka: extracellular vesicles) that contain specific protein signatures, which can indicate the behaviour and phenotype of the respective cells of origin. -We have identified and described certain vesicle-associated biomarkers that correspond to the most aggressive brain cancers. -Our results can provide insights for the development of new diagnostic and therapeutic methods as well as personalized treatment strategies (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Duke, Immunotherapy, NEJM, Vaccine Studies / 26.06.2018

MedicalResearch.com Interview with: Annick Desjardins, M.D., F.R.C.P.C. Associate Professor of Neurology Associate Professor of Neurosurgery Director of Clinical Research The Preston Robert Tisch Brain Tumor Center at Duke Duke University School of Medicine Durham, NC 27710 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The poliovirus receptor (CD155) is an onco-fetal cell adhesion molecule with widespread expression in all solid tumors and particularly in primary CNS tumors (adult and pediatric). Recombinant nonpathogenic polio–rhinovirus chimera (PVSRIPO) was generated by replacing a critical piece of the genetic information from the Sabin type 1 polio vaccine, making PVSRIPO incapable of harming or killing normal brain cells, but toxic/lethal in cancer cells. In preclinical models, it has been demonstrated that the infection of tumor cells, leads to the release of danger signals, which triggers a recruitment of dendritic/CD4/CD8 T cells and a destruction of tumor cells by anti-tumor T cells. The manuscript reports the results of the phase 1 trial of PVSRSIPO in recurrent WHO grade IV malignant glioma patients. Adult patients with recurrence of a single glioblastoma lesion, 1-5.5cm in dimension, in a non-eloquent area of the brain, were enrolled on study. PVSRIPO is injected slowly over 6.5 hours directly into the tumor via a small catheter inserted via a small bur hole. Once intratumoral injection is completed, the catheter is removed and patients are observed for localized tumor inflammation, followed by tumor contraction. A total of 61 patients were treated on study, 9 patients in a dose escalation phase and 52 in a dose expansion phase. Side effects observed were in relation to the localized inflammation of the tumor and depending on the cerebral functions in close proximity to the tumor: headaches, visual field changes, hemiparesis, etc. One patient experienced a brain hemorrhage at the time of catheter removal, which triggered right sided weakness and aphasia. The patient remained alive 57.5 months after PVSRIPO infusion at data cutoff of March 20th, 2018. Two on-study death were observed, a patient died from cerebral edema and seizures, which was later found to be due to tumor progression, and one patient died from the complications of an intracranial hemorrhage while receiving anticoagulation and bevacizumab. The median overall survival among all 61 patients who received PVSRIPO was 12.5 months (95% CI, 9.9 to 15.2), comparatively to 11.3 months (95% CI, 9.8 to 12.5) in a historical control group of patients treated at Duke and who would have met eligibility on trial, would have the trial been available to them. At 24 months, the survival plateaued in patients treated with PVSRIPO with an overall survival rate of 21% (95% CI, 11 to 33) at 24 months and 36 months in PVSRIPO treated patients, while overall survival in the historical control group continued to decline, with an overall survival rates of 14% (95% CI, 8 to 21) at 24 months and 4% (95% CI, 1 to 9) at 36 months in the historical control group.  (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Chemotherapy / 22.01.2018

MedicalResearch.com Interview with: Bakhos Tannous, PhD Neuro-Oncology Division Department of Neurology MGH MedicalResearch.com: What is the background for this study? What are the main findings? Response: Glioblastoma (GBM) is the most common and most aggressive type of brain tumors in adults. Over the last two decades, the major improvement in the treatment for GBM has been the addition of the chemotherapeutic temozolomide (TMZ) to the standard of care (surgery and radiation), however, despite this aggressive therapy, over 90% of patients die within five years after diagnosis. Further, only about half of GBM patients really benefit from TMZ treatment, while the other half are somewhat resistant to TMZ since their tumor endogenously carry a DNA repair mechanism that removes DNA adducts caused by TMZ. We therefore wanted to find a combination therapy that overcomes TMZ resistance and works in all GBM patient populations, with a fast transition to the clinic. Through a repurposing drug screening aiming at recycling of old known drugs for new therapies, we found that the FDA-approved drug hydroxyurea to synergizes with temozolomide in patient-derived GBM cells from newly diagnosed and recurrent tumors, irrespective of their DNA repair mechanism. The combination of hydroxyurea and TMZ worked very well in all different patient cell population tested, and was not specific to one subtype, and lead to a significant increase in survival rate in different mouse models. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Radiation Therapy / 20.02.2017

MedicalResearch.com Interview with: N. Scott Litofsky, M.D. Chief of the Division of Neurological Surgery University of Missouri School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Radiosurgery is being used more often for treatment of brain metastases to avoid potential side effects of whole-brain radiation, such as cognition and mobility impairment. After surgical resection of a brain metastases, some radiation treatment is generally needed to control brain disease. Few studies have directly compared efficacy of tumor control between surgery followed by whole-brain radiation and surgery followed by radiosurgery. Our objective was to compare outcomes in two groups of patients – one whose brain metastasis was treated with surgery followed by whole-brain radiation and one whose surgery was followed by radiosurgery to the post-operative tumor bed. We found that tumor control was similar for both groups, with survival actually better in the radiosurgery group. The complications of treatment were similar. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Radiation Therapy, Yale / 30.09.2016

MedicalResearch.com Interview with: Nataniel Lester-Coll, MD Chief Resident in Radiation Oncology at Yale New Haven, Connecticut  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Recurrent Glioblastoma Multiforme (GBM) has limited treatment options and the prognosis is poor. Mibefradil diydrochloride was identified using a high-throughput compound screen for DNA double stranded break repair inhibitors. Mibefradil was found to radiosensitize GBM tumor cells in vitro and in vivo. Based on these findings, we sought to determine the maximum tolerated dose of mibefradil and radiation therapy in a Phase I recurrent GBM study. Eligible patients with recurrent  Glioblastoma Multiforme received Mibefradil over a 17 day period, with hypofractionated radiation (600 cGy x 5 fractions). There are 18 patients currently enrolled who have completed treatment. Thus far, there is no clear evidence of radionecrosis. A final dose level of 200 mg/day was reached as the maximum tolerated dose. The drug was very well tolerated at this dose. We saw intriguing evidence of enhanced local control in selected cases. Patients enrolled in a translational substudy who received Mibefradil prior to surgery were found to have adequate levels of Mibefradil in resected brain tumor tissue. (more…)
Abuse and Neglect, Author Interviews, Brain Cancer - Brain Tumors / 06.08.2016

Novocure is the developer of Optune, which uses Tumor Treating Fields to treat cancer. Tumor Treating Fields, or TTFields, are low intensity, alternating electric fields within the intermediate frequency range. TTFields disrupt cell division through physical interactions with key molecules during mitosis. This non-invasive treatment targets solid tumors. MedicalResearch.com: What is the background for this study? What are the main findings? Response: The National Comprehensive Cancer Network (NCCN) has recommended Optune as a standard treatment option for newly diagnosed glioblastoma (GBM) in its Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers. NCCN panel members designated Optune together with temozolomide as a category 2A treatment for newly diagnosed GBM for patients with good performance status, indicating uniform consensus among panel members to add Optune to the guidelines for newly diagnosed GBM. Optune has been included in the NCCN Guidelines as a category 2B treatment option for recurrent GBM since 2015. The recommendation follows the publication of Novocure’s EF-14 phase 3 pivotal trial data in The Journal of the American Medical Association (JAMA) in December, 2015. The EF-14 phase 3 pivotal trial demonstrated that adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival in newly diagnosed GBM. Glioblastoma, also called glioblastoma multiforme, or GBM, is a type of primary brain cancer. Approximately 12,500 GBM tumors, or tumors that may transform into GBM, are diagnosed in the U.S. each year. GBM is the most common type of primary brain cancer in adults. It is more likely to appear in older adults and to affect men than women. GBM is one of the deadliest forms of cancer, with patients typically not surviving beyond 15 months after diagnosis. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, JAMA / 16.12.2015

MedicalResearch.com Interview with: Roger Stupp, MD Professor & Chairman Department of Oncology & Cancer Center University of Zurich & University Hospital Zurich (USZ) Zürich / Switzerland Medical Research: What is the background for this study? Dr. Stupp: Tumor Treating Fields are an entirely novel modality in cancer treatment. Over 10 years ago researchers demonstrated that alternating electrical fields will block cell growth, interfere with organelle assembly, in particular perturb the spindle apparatus and cell division, all leading to mitotic arrest and ultimately apoptosis. This was shown in vitro, but importantly also in vivo animal models including not only mice and rats, but also hamsters and rabbits with deep seated solid tumours. So the question was whether we can demonstrate such an effect also in the clinic. Glioblastoma are locally invasive and aggressive tumours in the brain. They usually do not metastasise however they grow diffusely within the CNS and despite the best possible surgery, radiation and chemotherapy virtually always recur. We thus applied alternating electrical fields therapy, so called Tumor Treating Fields to the scalp of patients with newly diagnosed glioblastoma. After the end of standard chemoradiotherapy (TMZ/RT), patients were randomized to receive either standard maintenance TMZ-chemotherapy alone or in combination with TTFields. Almost 700 patients were randomized, here we report on a preplanned interim analysis looking at the first 315 patients included once they were followed for at least 18 months. The data on the first 315 patients are mature and allowed the IDMC to conclude that the trial should be stopped and the results made available. Medical Research: What are the main findings? Dr. Stupp: The study demonstrated a consistent prolongation of both progression-free and also of overall survival for patients who have been treated with TTFields in addition to standard therapy. The median progression-free survival and overall survival were prolonged by 3 months, translating to an absolute increase in overall survival at 2 years of 14%, from 29% to 43%. Or a hazard ratio of 0.74 for overall survival and of 0.62 for progression-free survival. (more…)
Author Interviews, Cancer Research, MD Anderson, PNAS / 04.03.2015

MedicalResearch.com Interview with: Kristen Turner PhD. (first author) and Wei Zhang, Ph.D. Professor Department of Pathology Director, Cancer Genomics Core Lab University of Texas MD Anderson Cancer Center Houston, Texas 77030 Medical Research: What is the background for this study? What are the main findings? Response: Glioblastoma (GBM) is the most commonly diagnosed type of brain tumor and is among the most aggressive and challenging cancer types to treat. The traditional approaches to combat this pervasive cancer include surgery combined with radiation and chemotherapy (temozolomide); yet, most will succumb to the disease in just over one year. In this study, we investigated the Akt family of proteins that are known to be highly active in the majority of Glioblastoma cases. We compared each Akt family member and its ability to initiate glioma progression. We discovered that activation of the third Akt member (Akt3) led to glioma progression and very aggressive tumors. We then studied these tumors to compare their molecular attributes and found evidence of increased DNA repair. Finally, we discovered that the Akt3-induced DNA repair function led to increased survival of Glioblastoma cells after treatment with the DNA damaging agents, radiation and temozolomide. (more…)