Projects Funded
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 $10 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.
2015:
Dr. Sanaz Memarzadeh, UCLA Broad Stem Cell Research Center
Grant Amount: $456,000
Sanaz Memarzadeh, MD, PhD, presented an opportunity for PHASE ONE to support a truly novel and promising ovarian cancer research study at the UCLA Broad Stem Cell Research Center. We are pleased to announce our two-year commitment of $300,000 in support of this innovative new approach. In addition, supporters pledged “I DO” and joined us by directly adding their own donations to her work using smartphones at our 15th Annual Gala or donating online, bringing in an additional $156,000.
Ovarian tumors account for about 3% of all malignancies in women, but are responsible for a disproportionately large number of cancer-related deaths. Ovarian cancer research has been chronically underfunded, compounding the challenge and perpetuating the risk to women. PHASE ONE’s grant will have a significant impact in beginning to reverse this situation.
Ovarian cancers are particularly dangerous because they are detected late. Ovarian cancer symptoms are often non-specific and can resemble other common ailments. Incredibly, there is no definitive screening test for ovarian cancer; tumors cannot be detected at an early stage.
We now know that most, if not all, cancers arise from cancer stem cells. Conventional therapies target rapidly dividing tumor cells, but cancer stem cells have the means to escape chemo and radiation. At some point, the cancer stem cells begin to self-renew, creating a new tumor.
The standard of care is surgical removal followed by chemotherapy. However, most patients relapse within one year and many succumb to ovarian cancer within five years. These tumors contain cells that exhibit stem cell-like properties and resist existing therapies. While these cells are a tiny fraction of the tumor mass, they are entirely responsible for initiating its regrowth.
Dr. Memarzadeh and her team have made major progress in isolating these stem cell-like catalysts, and are testing ways of eliminating them through enhanced chemotherapy. They envision a handful of strategies to individualize a patient’s care based on tumor analysis. With support from PHASE ONE, Dr. Memarzadeh is moving the first of these therapeutic strategies into clinical trial.
“My experience caring for patients with ovarian and other gynecological cancers is what motivates me to find more effective treatments to replace or compliment conventional therapies,” said Dr. Memarzadeh
INAUGURAL PHASE ONE TIA PALERMO MEMORIAL ENDOWMENT GRANT
Testicular Cancer Awareness Initiative of the Adolescent and Young Adult Cancer Program at USC
Grant Amount: $25,000
When longtime board member and former chair Tia Palermo passed away in 2012 following an 11-year battle with cancer, her family joined PHASE ONE in raising funds for a multi-million dollar endowment in her memory.
Funds from “PHASE ONE’s Tia Palermo Memorial Endowment” support three different programs:
- Tia’s Hope (www.tiashope.org), which provides gifts and support to children at hospitals throughout the country,
- PHASE ONE grants that it funds within the foundation’s original mission
- Small size grants that typically do not exceed $50,000.00 to support research, treatment and cancer awareness programs in our community that can be outside of the original PHASE ONE mission.
PHASE ONE’s first endowment grant was made in 2015 to the USC Norris Adolescent and Young Adult (AYA) cancer program’s new testicular cancer awareness initiative. The initiative is a collaborative community project with the Los Angeles Unified School District (LAUSD) and the University of California, Los Angeles (UCLA).
With the funds from the Phase One grant, in the fall of 2015, AYA initiated a pilot program with the LAUSD and UCLA aimed at increasing awareness of testicular cancer and among school-age students.
In the past several decades, cancers occurring in childhood have been the focus of cancer research and treatment programs worldwide. Unfortunately less attention has been given to adolescent and young adult (AYA) patients (ages 15-39) and cancer remains the number one disease killer within this age group. Because testicular cancer is one of the most common cancers diagnosed in young men, increasing awareness and early detection is a top educational priority of the initiative.
LAUSD is the nation’s second largest school district with an annual enrollment of approximately 651,000 kids in 1,188 schools. The district provides a semester-long comprehensive health education courses to all Grade 7 and 9 students who attend its schools. The courses are taught by credentialed health teachers. While the currently adopted curriculum used by the LAUSD health course contains content related to testicular cancer, the health textbook is ten years old, which is three years past a standard new adoption.
The initiative developed new project based health lessons focused on testicular cancer awareness to complement the current LAUSD health curriculum. Following the completion of the testicular cancer curriculum, professional development, technical assistance, and follow up support to the LAUSD health educators on project and content as they implement and incorporate these materials into their program, is planned. The newly developed curriculum was then piloted in the fall of 2015 in a minimum of three schools with the goal of expanding it to additional schools the following year and ultimately to every school in the LAUSD system.
PHASE ONE is proud to provide the seed grant of $25,000 to fund this new testicular cancer awareness initiative that ultimately will help educate and provide greater awareness to every child in the LAUSD.
2014:
Dr. Richard Tuli, Cedars-Sinai Medical Center
Grant Amount: $323,423
Pancreatic adenocarcinoma is a devastating disease with the lowest survival rate of any solid cancer. Gemcitabine chemotherapy and radiotherapy given concurrently remain the mainstay treatments for patients with locally advanced pancreatic cancer, which cannot be removed by surgery, but also has not spread to other areas of the body. Both gemcitabine and radiotherapy kill tumor cells by interfering with their DNA, the genetic blueprint. Veliparib is a poly (ADP-ribose) polymerase (PARP)1/2 inhibitor; PARP1/2 proteins are also involved in DNA repair. Studies have shown that inhibiting PARP1/2 activity can significantly enhance the effects of radiotherapy and chemotherapy in killing tumor cells. Our own laboratory work has shown excellent synergy between veliparib (a PARP inhibitor), radiotherapy and gemcitabine in killing pancreatic cancer cells grown in culture, and in prolonging survival in mice with pancreatic tumors.
Based upon these promising results and with the generous support of the Phase One Foundation and Diane V. Allen, we are currently enrolling patients in a first-in-human, investigational clinical study (phase I) to test the safety and efficacy of veliparib in combination with gemcitabine and radiotherapy in patients with locally advanced pancreatic cancer. Prior to and during therapy, patient tumor and blood samples will also be tested for levels of different DNA repair proteins and mutations, such as BRCA1/2. This molecular “signature” will hopefully serve as a “biomarker” to predict how the patient and tumor are responding to treatment. We are hopeful that we will be able to select out the subset of favorable patients who respond to this regimen, and design future studies (phase 2/3) by “personalizing” treatments using PARP1/2 inhibitors.
Dr. Jana Portnow, City of Hope
Grant Amount: $66,000
Dr. Jana Portnow has been the fortunate recipient of prior funding from the PHASE ONE Foundation in support of two important brain tumor research projects. One of these projects involved developing a technique to measure chemotherapy levels in brain tumor patients using microdialysis catheters. Dr. Portnow’s other ongoing research interest is taking into clinical trials a promising new treatment for gliomas that involves the use of genetically-modified human neural stem cells as vehicles for drug delivery to the brain. The brain tumor research team at City of Hope modified an established human neural stem cell line to carry an enzyme called cytosine deaminase (CD) which can convert an inactive prodrug, 5-fluorocytosine (5-FC), to the chemotherapy agent 5-fluorouracil (5-FU). With support from the PHASE ONE Foundation, Dr. Portnow performed a first-in-human study of these CD-expressing neural stem cells in combination with oral 5-FC in patients with recurrent high-grade gliomas.
Based on the results of this pilot-feasibility study, Dr. Portnow is performing a formal phase I study of these CD-expressing neural stem cells in combination with oral 5-FC in patients with recurrent high grade gliomas. In addition to escalating the dose of neural stem cells, this study will assess the feasibility of giving repeat doses of neural stem cells through an indwelling catheter which will be placed at the time of surgery.
Guests at the 2014 Gala donated $66,000 toward that study, and the first patient was enrolled that fall.
2013:
Dr. Anna Pawlowska, City of Hope
Grant Amount: $37,000
In a novel approach, guests at the 2013 Phase One Gala DIRECTLY donated $37,000 to help fund part of a trial for patients with Ewing's sarcoma. Ewing's sarcoma is the second most common primary bone tumor in children and adolescents. While advances in treatment have increased survival rates for children with localized disease to nearly 70 percent, fewer than 30 percent of patients who experience relapse or the spread of their cancer survive. In addition to these grim statistics, there is no nationally accepted “gold standard” of treatment for patients with advanced Ewing's sarcoma. More effective therapies are urgently needed to save the lives of young patients.
City of Hope will be launching a five-year pilot clinical trial to study the effectiveness of a promising treatment for high-risk patients with advanced Ewing's sarcoma: whole-body MRI-guided radiation therapy followed by autologous hematopoietic cell transplant, with a novel combination of high-dose chemotherapy. Led by Anna Pawlowska, M.D., Clinical Professor of Pediatrics, the proposed study will assess whether this therapy is feasible, safe and likely to increase patient survival rates. A similar approach tested in Germany and Austria increased children's survival rate to 70 percent after two years and 56 percent after three years with minimal toxicity, but this approach has never been tested in the United States.
The funds raised will support MRI tests for patients not covered by their insurance and/or support a portion of the salary of a Clinical Research Assistant. This critical seed funding would help young patients with Ewing's sarcoma access a promising new therapy now and start collecting the patient data needed to secure additional public and private funding for future years of the trial.
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.
2012:
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.
2011:
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.”
2010:
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.
2007-2009:
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.
2006:
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.
2005:
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.
2004:
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.
2003:
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.
2002:
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.
2001:
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.