PHASE ONE is dedicated to ensuring that the Southern California community has access to the most promising novel therapies available for those diagnosed with cancer. To that end, we have raised more than $9 million in support of new and innovative clinical trials and treatment. The findings of these studies will ideally lead to further research or independently-funded projects.
Dr. Karim Chamie, University of California Los Angeles
Grant Amount: $142,350
Dr. Karim Chamie, with UCLA Urology, is working to combat the rapid increase in recent years of urothelial cancer by investigating a potentially new treatment method involving a hydrogel polymer (chemical compound), which is liquid at room temperature, mixed with chemotherapy to treat this difficult-to-detect and highly reoccurring form of cancer. The polymer-chemotherapy combination takes on the shape of the cavity of interest (such as a kidney) at body temperature and has the potential to deliver chemotherapy to the targeted site while minimizing side-effects. The polymer can also be mixed with a dye that binds to tumor cells to facilitate detection of tumor cells within a specific organ. Traditionally, what has been most challenging in treating this type of cancer is the ability to deliver the chemotherapeutic agent at a high concentration level to the exact tumor site. This new discovery has the potential to overcome the previous challenge by using the polymer-chemotherapy directly to the targeted site. Dr. Chamie and his team are optimistic in pursing this study and are grateful to the Phase One Foundation for supporting these efforts.
Dr. Joseph Riss, University of California Los Angeles
Grant Amount: $310,000
Despite advancement in targeted treatments, metastatic kidney cancer poses a therapeutic challenge due to its resistance to conventional models of treatment. As long-term survival for patients with metastatic kidney cancer remains poor, UCLA Urology’s Allan Pantuck, MD and Arie Belldegrun, MD, along with Joseph Riss, PhD, have been working for years to develop innovative methods of therapy. With the assistance of critical funding provided by the Phase One Foundation, this research team developed a kidney cancer vaccine that was recently approved by the FDA and given to the first patient in February 2013. Even with this grand milestone, the researchers must now monitor the effectiveness of the vaccine, especially given the kidney tumor’s resistance to current therapeutics. With the continuous support of the Phase One Foundation, Dr. Riss and his team will use previously identified indicators to develop diagnostic tools for monitoring the new treatment and aim to develop a next-generation vaccine that will combat tumor resistance in metastatic kidney cancer.
Dr. Antoni Ribas, University of California Los Angeles
Grant Amount: $294,400
With the support of the Phase One Foundation we will conduct a phase 1 clinical trial (MART-1 F5 TCR Engineered Adoptive Cell Transfer Therapy with CTLA4 Blockade) with the goal of genetically programming the human immune system to efficiently target cancer cells in patients with advanced stage melanoma, the deadliest of skin cancers. This clinical trial builds upon the experience at UCLA over the past 3 years in the use of T cell receptor (TCR) engineered adoptive cell transfer therapy. This therapy is manufactured in-house and results in the generation of a large army of immune system cells that are genetically redirected to recognize and kill melanoma. With this therapy we have noted high initial response rates, but tumors come back. A major limitation has been a progressive decrease in the antitumor functionality of the TCR engineered immune cells. The antibody tremelimumab blocks a major negative regulator in immune cells and will be tested with the goal of maintaining the cancer killing functionality of the TCR engineered lymphocytes given to patients. This protocol has administrative approval by the UCLA regulatory committees and it has already been filed and approved by the Food and Drug Administration.
P.R. Lowenstein, M.D. PhD and Maria G. Castro, PhD
Department of Neurosurgery and Cell and Developmental Biology,
The University of Michigan School of Medicine, Ann Arbor, Michigan
Grant Amount: $216,000
Highly malignant brain tumors are uniformly lethal. Patients usually survive less than 2 years post-diagnosis, with very few still alive 5 years later. In spite of constant developments in surgery, radiotherapy and chemotherapy a breakthrough for this particularly aggressive cancer has not been yet discovered. Over the last ten years we have developed a novel approach for the treatment of brain tumors. Based on an evolutionary and developmental understanding of the structure and function of the brain immune system, we decided to restitute to the brain those immune cells normally absent from it, as a potential new approach to treat brain tumors. The immune cells normally absent from the brain are those in charge of turning on the anti-tumor immune response. Their absence from the brain helps us explain why normally anti-brain tumor immune responses are ineffective. By attracting those specific immune cells to the brain and the brain tumors, we expect them to identify brain tumor antigens and unleash a therapeutically effective immune attack to eliminate brain tumors. To achieve this we have turned adenoviruses which normally can cause lung infections and other diseases into therapeutic agents. We have engineered the viruses to deliver directly to the brain and the brain tumors a protein that will recruit the missing immune cells to the brain to start a clinically effective immune response. As our work uses viruses as agents of treatment to induce immune responses, our therapeutic approach is described as a “combined gene-and immune therapy”. Following more than ten years of development and experimental testing we are now ready to start clinical trials in patients suffering from glioblastoma multiforme. With very generous support from the Phase One Foundation, we are now on the threshold of starting the first ever clinical trials of this new therapeutic approach for the treatment of deadly highly malignant brain tumors. The proposed trial, which was approved by the Food and Drug Administration on April 7, 2011, is currently undergoing the final evaluations by the Institutional Biosafety Committee, and the Institutional Review Board for Clinical Trials. We expect these evaluations to be finalized within the next few weeks. Once our trial has cleared all necessary Committee reviews, it will be ready to start. Phase One has thus provided the green light to move the dreams of two basic scientists into the challenging arena of clinical trials. As the trial starts enrolling patients we will look forward to keeping Phase One abreast of all therapeutic developments. We hope, and for the sake of the patients, we pray, that treating the first patients may represent in Winston Churchill’s prophetic words, “Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning.”
Children's Hospital Los Angeles
Grant Amount: $410,000
In February, Phase One announced our latest grant, $410,000 over two years to fund a Phase I study at Children's Hospital Los Angeles. The study, led by Dr. Stuart E. Siegel, is of AC220 for children with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). This grant will provide an opportunity in getting a second generation FLT3 inhibitor drug tested in a pediatric population that truly focuses on the concept of FLT3 inhibition in high-risk ALL and AML patents. The goal of the study is to obtain sufficient laboratory and clinical data to enable the design of a larger Phase II study. Results from this study would also leverage funding to support the Phase II part of this project from both the National Cancer Institute, as well as the pharmaceutical company Ambit that makes the drug.
The Premiere Oncology Foundation Lung Cancer Initiative
Grant Amount: $266,500
Premiere Oncology Foundation, a non-profit dedicated to cancer research, integrative medicine, patient/family support services and community education, will utilize the grant to support a comprehensive lung cancer program to include multi-disciplinary research.
Lung cancer is the world's top cancer killer, claiming more than 1.3 million lives per year, yet few financial resources have been dedicated to this disease. The Premiere Oncology Foundation Lung Cancer Initiative focuses on the use of FDA-sanctioned novel treatment regimens in collaboration with experts in the field of lung cancer detection and treatment. The program will foster dialog among practitioners caring for lung cancer patients, and provide a means for seamless interaction with medical and radiation oncologists, thoracic surgeons, radiologists, pulmonologists and primary care physicians caring for these patients.
Dedicated to whole-patient care and recognized for expediting clinical trials, Premiere's flagship cancer center in Santa Monica offers patients the newest cutting-edge treatments, rapid access to novel, internationally available therapies and integrative medicine all under one roof. Additionally, Premiere provides services in its Scottsdale, Arizona center and research affiliation with Pacific Hematology & Oncology Associates in San Diego.
The Samuel Oschin Comprehensive Cancer Institute
Cedars-Sinai Medical Center
Grant Amount: $2,000,000
Internationally renowned cancer researcher Steven Piantadosi, MD, PhD, was named the inaugural Phase ONE Foundation Endowed Chair of the Samuel Oschin Comprehensive Cancer Institute (SOCCI) at Cedars-Sinai Medical Center at a ceremony February 6, 2008. SOCCI provides cutting edge cancer clinical trials and sub-cellular research, in addition to state-of-the-art patient care. Its research efforts are focused on developing breakthroughs that translate as efficiently as possible into new methods for the treatment of cancers of the lung, brain, colon, prostate, pancreas, breast, spine, ovaries, pituitary, thyroid and blood system, plus melanoma and other cancers.
With this endowment, Dr. Piantadosi will define and direct the activities of the Institute and serve as a key figure in framing the national debate about cancer, while having a decided impact on the direction and success of new research.
City of Hope Comprehensive Cancer Center,
Grant Amount: $345,000
The City of Hope Division of Medical Oncology, Chaired by Robert Figlin MD., and its Department of Clinical and Molecular Pharmacology, directed by Yun Yen MD, PhD., is the City of Hope Comprehensive Cancer Center equivalent to a Phase 1 Solid Tumor Program. In this program is the exciting translation of molecules from the laboratory to the clinic.
City of Hope will use the Phase One funds to support novel Phase 1 clinical trials developed in collaboration with the Department of Clinical and Molecular Pharmacology. These resources would be utilized to fund novel protocols or existing protocols where additional funds could translate findings from the laboratory to the clinic. Support for novel "NEW" programs (25-50K/year for two years) in Clinical and Molecular Pharmacology that can reach the clinic during the two years of the award, and bring innovation from our laboratories will be the highest priority.
The City of Hope Comprehensive Cancer Center's Phase1 Program has a commitment to the Developmental Therapeutics and Hematologic Malignancies Programs directed by Yun Yen MD, PhD, Richard Jove PhD, and Steven Forman MD. City of Hope will establish competitive awards (25-50K/year for two years) that combine a laboratory and clinical Principal Investigator that translate laboratory observations into the clinic during this period. Programs in Solid Tumors and Hematologic Malignancies including lymphomas, in both adults and children would be included.
Kuk-Wha Lee, M.D. PhD
Grant Amount: $250,000
Dr. Lee is a graduate of the Medical Scientist Training program at Loma Linda University School of Medicine, obtaining her PhD and MD. Her clinical training is in pediatrics and she was fellowship trained in Pediatric Endocrinology at the Mattel Children's Hospital at UCLA. In training she was the recipient of the prestigious Giannini Foundation Fellowship, Stein-Oppenheimer Award, and the LWPES Clinical Scholar Award for her research. In addition, she is the recipient of the UCLA Prostate Cancer SPORE Career Development Award for her research in cellular and animal models of human prostate cancer.
Her laboratory studies the biological functions of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) and its binding partners in cancer biology, specifically prostate cancer. Specifically, she studies the molecular mechanisms by which this molecule enters cells; targets specific areas within cancer cells (e.g. the nucleus and mitochondria); and initiates the programmed cell death cascade.
Unique assays in their laboratory have been developed to study serum levels of these molecules and also have developed unique transgenic and knockout mouse models of human disease. Based on preliminary work published from their laboratory the plan is to initiate a phase 1 trial of IGFBP-3 in men with prostate cancer in the near future.
Karen Reckamp, M.D.
Grant Amount: $500,000
A Phase 1 Trial of Vaccine Therapy with Lung Cancer
With her mentor, Steven Dubinett, M.D., Director of the UCLA Lung Cancer Program, Dr. Redcamp's efforts are in the immunologic treatment of lung cancer through novel genetic-based immunologic stimulation. Her proposal is for a Phase 1 Clinical Trial of the intratumoral administration of an immune stimulant called a chemokine to induce an immune response that could yield immunity to this cancer.
Dr. Arie Belldegrun & Dr. Alan Pantuck
Grant Amount: $250,000
UCLA Department of Urology Specializing in New Treatments for Kidney and other genitourinary cancers, particularly vaccine therapies directed against newly identified targets.
Dr. Heinz-Josef Lenz & Dr. Daniel Vallboehmer
Grant Amount: $250,000
USC/Norris Comprehensive Cancer Center Specialists In Gastro-Intestinal Malignancy Searching for molecular markers to predict prognosis and response to therapy.
Dr. Charles Sawyers & Dr. Ingo Mellinghoff
Grant Amount: $250,000
UCLA Jonsson Comprehensive Cancer Center Hematology/Oncology Translational Scientists working on molecular mechanisms that underlie the development and spread of cancer.
Dr. David Agus & Dr. Mitchell Gross
Grant Amount: $250,000
Cedars Sinai Prostate Cancer Program Looking at innovative treatments for prostate cancer and using information technology systems to identify molecular markers for response to therapy.
Dr. Lee Rosen
Cancer Institute Medical Group
Grant Amount: $276,250
In 2003, Dr. Lee Rosen conducted a Phase I study of a medication that could theoretically shut down the development of new blood vessels from which tumors grow and possibly spread. Using a series of radiographic assessments including CT/MRI/Bone scans, etc. as well as conventional scans such as CT/MRI, Dr. Rosen and his colleagues at the Cancer Institute Medical Group, examined the response of their patients to this new medication and to what degree. He also found the use of PET scans, which look at changes in tumor metabolic activity rather than size, is very effective, PHASE ONE has been sponsoring a trial which will look at whether a combination of PET/CT scans can aid in the assessment of the drug's efficacy more quickly than conventional CT scanning alone.
Dr. Sven de Vos, Dr. Christos Emmanouilides, Dr. William H. McBride and Dr. Jonathan W. Said
Jonsson Comprehensive Cancer Center
Grant Amount: $150,000
PHASE ONE sponsored an Indisciplinary Grant to study the use of the Proteasome Inhibitor PS-341 in the treatment of refractory diffuse large B-cell lymphomas in terms of clinical efficacy, mechanisms of resistance and new models of combination therapy. The study was conducted by principal investigator, Sven de Vos, M.D., and co-investigators, Christos Emmanouilides, M.D., William H. McBride, M.D. and Jonathan W. Said, M.D. at the Jonsson Comprehensive Cancer Center.
Dr. Carolyn Britten
Jonsson Comprehensive Cancer Center
Grant Amount: $175,000
PHASE ONE sponsored the recruitment of a full-time clinical research physician for a full year. Highly respected oncologist, Dr. Carolyn Britten, joined the faculty of the Jonsson Comprehensive Cancer Center in early 2001 and PHASE ONE funded her research for one year. Dr. Britten is involved in four promising Phase I trials testing new and unique therapeutic strategies in signal transduction and angiogenesis.