Tag Archives: Daniel D. Von Hoff

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TGen, SHC begin clinical trial for anti-tumor drug

The Virginia G. Piper Cancer Center at Scottsdale Healthcare and the Translational Genomics Research Institute (TGen) are studying the safety and effectiveness of a new drug, AG-120, for treatment of patients with solid tumors, especially those with brain tumors and gallbladder bile duct cancer.

“AG-120 is designed specifically for those patients who carry the IDH1 gene mutation,” said Dr. Daniel D. Von Hoff, Distinguished Professor and Physician-In-Chief at TGen, and Chief Scientific Officer for the Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, a partnership between Scottsdale Healthcare and TGen that delivers new treatments to cancer patients based on precision medicine.

The IDH1 gene mutation is most commonly found in gliomas, which make up the largest group of “primary” brain tumors, those that start in the brain. Gliomas include all tumors arising from the gluey or supportive tissue of the brain. They represent about 30 percent of all brain tumors, and about 80 percent of all malignant brain tumors.

As with all brain cancers, gliomas are difficult to treat and many grow back after surgery, radiation and standard of care chemotherapy. Many drugs cannot get to the brain because of a filtering mechanism in the body called the blood-brain barrier.

“There is a great need for more effective treatments for patients with gliomas and other solid tumors, such as gallbladder bile duct cancer,” said Dr. Von Hoff, who is the Principal Investigator for AG-120 clinical trial. This study will enroll as many as 50 patients. Researchers will use precision medicine to match treatments to patient’s specific genomic, or molecular, makeups.

Mutations in isocitrate dehydrogenase (IDH) 1 and 2, originally discovered in 2008, occur in the vast majority of low-grade gliomas and secondary high-grade gliomas. IDH mutations are oncogenic, meaning they have the potential to cause cancer. These mutations occur early in the formation of gliomas and in gallbladder bile duct cancer.

AG-120 is produced by Agios Pharmaceuticals Inc., based in Cambridge, Mass.

IDH1 is a metabolic enzyme identified by Agios as a protein that is mutated in a wide range of malignant tumors. Agios and its collaborators recently demonstrated that IDH1 mutations initiate and drive cancer growth by blocking differentiation, or maturation, of primitive cells. According to Agios, the inhibition of these mutated proteins may lead to clinical benefit for those cancer patients whose tumors carry them.

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Pancreatic cancer drug successfully tested by TGen

A clinical trial conducted by researchers at the Virginia G. Piper Cancer Center Clinical Trials, a partnership between Scottsdale Healthcare and the Translational Genomics Research Institute (TGen), showed that a new drug called MM-398, given in combination with 5-flourouracil (5FU) and leucovorin, produced a significant overall survival rate in patients with advanced, previously-treated pancreatic cancer.

The NAPOLI-1 (NAnoliPOsomaL Irinotecan) Phase 3 study — a final confirmation of a drug’s safety and effectiveness — was conducted among patients with metastatic pancreatic cancer who previously received gemcitibine, which has been the standard-of-care therapy for such patients.

The study, sponsored by Merrimack Pharmaceuticals, evaluated 417 patients enrolled at more than 100 sites in North America, South America, Europe, Asia and Australia, including patients at the Virginia G. Piper Cancer Center at Scottsdale Healthcare. Merrimack expects to submit a New Drug Application this year to the U.S. Food and Drug Administration (FDA) for the MM-398 combination regimen.

“This demonstration of a survival benefit from the MM-398 plus 5-FU and leucovorin combination is particularly important given that we have very few treatment options for patients in this tough clinical setting,” said Dr. Daniel D. Von Hoff, MD, FACP, global principal investigator of the NAPOLI-1 study, Chief Scientific Officer for Scottsdale Healthcare’s Virginia G. Piper Cancer Center Clinical Trials and Physician-In-Chief and Distinguished Professor at TGen. “The results of the NAPOLI-1 study are important because of the critical need to help patients with this devastating illness and move forward towards FDA approval.”

The combination of MM-398 with 5-fluorouracil (5-FU) and leucovorin achieved an overall survival of 6.1 months, a 1.9 month improvement over the 4.2 month survival demonstrated by the control arm of 5-FU and leucovorin alone.

Each year in the U.S., nearly 46,000 people are diagnosed with pancreatic cancer, and more than 39,000 patients die, making it the fourth leading cause of cancer death. Only about 1 in 4 patients survive more than one year after diagnosis, and only 6 percent survivor more than five years.

Symptoms of pancreatic cancer usually do not appear until the cancer is in its late stages, making it difficult to treat. Once the disease spreads to other parts of the body, most patients are not candidates for surgery and receive chemotherapy as their primary treatment.

This study will be presented at the European Society for Medical Oncology World Conference on Gastrointestinal Cancer being held June 25-28 in Barcelona, Spain.

Patients seeking information about research studies may contact the Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare at 480-323-1339 or toll free at 1-877-273-3713 or e-mail: clinicaltrials@shc.org.

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SHC’s Von Hoff honored for cancer advances

In association with its 50th anniversary, the American Society of Clinical Oncology (ASCO) has named Daniel D. Von Hoff, M.D., FACP, one of ASCO’s 50 Oncology Luminaries, celebrating 50 doctors who over the past half-century have significantly advanced cancer care.

Dr. Von Hoff is Chief Scientific Officer for Scottsdale Healthcare’s Virginia G. Piper Cancer Center Clinical Trials and Physician-In-Chief and Distinguished Professor at Phoenix-based Translational Genomics Research Institute (TGen). He is an internationally recognized physician and scientist whose research during the past 30 years has contributed to the development of many anticancer agents that are routinely used in clinical practice. Among these drugs are fludarabine, mitoxantrone, paclitaxel, docetaxel, irinotecan, topotecan, nelarabine, gemcitabine, vismodegib, and nanoparticle paclitaxel.

ASCO was founded in 1964 by oncologists to improve the care of cancer patients. Profiles of the 50 Oncology Luminaries are being featured on the ASCO website, and their accomplishments will be celebrated at ASCO’s 50th annual meeting, May 30-June 3 in Chicago.

Although it is difficult to pick one highlight of his career, Dr. Von Hoff and his team played an instrumental role in the development of gemcitabine, the first drug to improve the survival of patients with stage IV pancreatic cancer. In 1997, they published the results of a clinical trial that showed that gemcitabine not only increased the rate of clinical benefit in patients with pancreatic cancer compared with fluorouracil (5-FU), but it also improved overall survival.

This work was followed by recognition of the activity of nab-paclitaxel plus gemcitabine against pancreatic cancer with the recent finding that that regimen also improved survival for patients with stage IV pancreatic cancer. On Sept. 6, 2013, the U.S. Food and Drug Administration (FDA) approved nab-paclitaxel as a frontline therapy for patients with advanced pancreatic cancer.

International clinical trials that led to the FDA’s approval were led by Dr. Von Hoff at Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, a partnership of Scottsdale Healthcare and TGen, at Scottsdale Healthcare Shea Medical Center in Scottsdale, Ariz.

Dr. Von Hoff has also been instrumental in the concept of development of personalized therapy for patients with refractory cancer based on using molecular techniques to profile their cancers. This work included the initial clinical trials to determine what percentage of patients could benefit from that approach.

Dr. Von Hoff has spent the past 30 years of his career leading teams in phase I trials and the development of new therapies, first as the founding director of the Institute for Drug Development at the Cancer Therapy and Research Center in San Antonio, then as the director of the Cancer Center and Professor of Medicine at the University of Arizona. He also is Professor of Medicine at the Mayo Clinic and serves as Chief Scientific Officer for US Oncology.

When Dr. Von Hoff was awarded ASCO’s David A. Karnofsky Memorial Award in 2010, he took several minutes at the beginning of his lecture to memorialize all of the patients that he and his team had lost during phase I trials the previous year, mentioning several of them by name. The gesture reflected what Dr. Von Hoff named as the greatest accomplishment of his career: working hard to help as many people as he could.

“I have been extremely fortunate to have many great (and incredibly patient) teachers, mentors, and co-workers,” Dr. Von Hoff said. “Truly though I think the greatest teachers and mentors for me have been those I have been privileged to care for.”