National Pediatric Cancer Foundation Inc

THE NPCF IS DEDICATED TO FUNDING RESEARCH TO ELIMINATE CHILDHOOD CANCER.

THE NATIONAL PEDIATRIC CANCER FOUNDATION FUNDS PEDIATRIC CANCER RESEARCH WITH THE GOAL OF LEADING TO THE TREATMENT AND ELIMINATION OF PEDIATRIC CANCER WORLDWIDE.WE ACCOMPLISH OUR MISSION THROUGH OUR RESEARCH INITIATIVE, THE SUNSHINE PROJECT, AN INNOVATIVE COLLABORATION OF 30 HOSPITALS NATIONWIDE. THIS COLLABORATIVE RESEARCH MODEL IS UNIQUE AND EFFECTIVE IN ACCELERATING THE DEVELOPMENT OF NEW TREATMENTS AGAINST CHILDHOOD CANCER.SEE SCHEDULE O FOR FURTHER PROGRAM SERVICE ACCOMPLISHMENTS.IN DEVELOPING THIS COLLABORATION, THE FOUNDATION HAS BROUGHT TOGETHER SOME OF THE COUNTRY'S LEADING INVESTIGATORS AND INSTITUTIONS TO DRIVE THE PROCESS OF FINDING A CURE. INVESTIGATORS ARE PERFORMING THREE VITAL PHASES OF RESEARCH SIMULTANEOUSLY: BASIC SCIENCE, TRANSLATIONAL RESEARCH AND CLINICAL TRIALS. THESE MAJOR RESEARCH COMPONENTS NOT ONLY ALLOW DOCTORS TO IDENTIFY NEW AGENTS IN FIGHTING CANCER, BUT ALSO HELP RESEARCHERS TO UNDERSTAND THE CANCER CELLS RESPONSE TO THE DRUG. THE NATIONAL PEDIATRIC CANCER FOUNDATION IS MAKING GREAT STRIDES IN ITS MISSION TO FIND A CURE FOR CHILDHOOD CANCER.CURRENT INITIATIVES OF THE SUNSHINE PROJECT ARE AS FOLLOWS:SARCOMA TRIALS (OSTEOSARCOMA, RHABDOMYOSARCOMA, EWING SARCOMA, NON-RHABDOMYOSARCOMA)1. PHASE II STUDY OF NAB-PACLITAXEL IN COMBINATION WITH GEMCITABINE FOR TREATMENT OF RECURRENT/REFRACTORY SARCOMA IN TEENAGERS AND YOUNG ADULTSTHIS TRIAL WILL LOOK AT THIS COMBINATION OF NAB-PACLITAXEL AND GEMCITABINE IN ITS ABILITY TO PREVENT THE FORMATION OR GROWTH OF TUMORS IN TEENAGERS AND YOUNG ADULTS WITH RELAPSED OR REFRACTORY OSTEOSARCOMA, EWING SARCOMA, RHABDOMYOSARCOMA AND OTHER SOFT TISSUE SARCOMA. THE TRIAL WILL ALSO LOOK AT THE LENGTH OF TIME DURING AND AFTER TREATMENT THAT THE DISEASE DOES NOT GET WORSE,AND DETERMINE IF NAB-PACLITAXEL COMBINED WITH GEMCITABINE IS SAFE AND TOLERABLE.2. A PHASE IB/II STUDY TO EVALUATE THE SAFETY, FEASIBILITY AND EFFICACY OF NIVOLUMAB OR NIVOLUMAB IN COMBINATION WITH AZACITIDINE IN PATIENTS WITH RECURRENT, RESECTABLE OSTEOSARCOMA - THIS WILL BE THE FIRST TIME BOTH DRUGS, NIVOLUMAB AND AZACITIDINE ARE BEING USED IN COMBINATION TO TREAT OSTEOSARCOMA3. EVOLUTIONARY INSPIRED THERAPY FOR NEWLY DIAGNOSED, METASTATIC, FUSION POSITIVE RHABDOMYOSARCOMAMETASTATIC, FUSION POSITIVE RHABDOMYOSARCOMA (RMS) HAVE A POOR OUTCOME WHICH IS WORSENED WITH ADDITIONAL RISK FACTORS COMMONLY CALLED THE OBERLIN CRITERIA. PATIENTS THAT MEET ALL 4 OBERLIN CRITERIA HAVE AN EVENT FREE SURVIVAL (EFS) OF LESS THAN 20% AT 2 YEARS. ALL THERAPEUTIC ARMS ON THIS STUDY ARE DESIGNED TO MEET THE SAME PRIMARY AIM OF IMPROVING THE 3 YEAR EVENT FREE SURVIVAL FROM 6% TO 35% FOR THESE PATIENTS. 4. PHASE 1 TRIAL OF THE LSD1 INHIBITOR SP-2577 IN PATIENTS WITH RELAPSED OR REFRACTORY EWING SARCOMA)THIS TRIAL IS A TARGETED TREATMENT FOR INDIVIDUALS DIAGNOSED WITH REFRACTORY OR RECURRENT EWING SARCOMA, AN AGGRESSIVE, SMALL ROUND BLUE CELL TUMOR TYPICALLY PRESENTING AS A PRIMARY BONE TUMOR IN CHILDREN AND YOUNG ADULTS.5. TINKS: A MULTI-INSTITUTION STUDY OF TGF IMPRINTED, EX VIVO EXPANDED UNIVERSAL DONOR NK CELL INFUSIONS AS ADOPTIVE IMMUNOTHERAPY IN COMBINATION WITH GEMCITABINE AND DOCETAXEL IN PATIENTS WITH RELAPSED OR REFRACTORY PEDIATRIC BONE AND SOFT TISSUE SARCOMAS (IN DEVELOPMENT) - TO DETERMINE THE SAFETY OF THE ADDITION OF ADOPTIVE TRANSFER OF UNIVERSAL DONOR, TGF IMPRINTED (TGFI), EXPANDED NK CELLS TO GEMCITABINE/DOCETAXEL (GEM/DOX) FOR TREATMENT OF RELAPSED AND REFRACTORY SARCOMAS.BRAIN TUMOR TRIAL1. ACTION : ADOPTIVE CELLULAR THERAPY FOLLOWING DOSE-INTENSIFIED TEMOZOLOMIDE IN NEWLY-DIAGNOSED PEDIATRIC HIGH-GRADE GLIOMAS - AN IMMUNOTHERAPY TRIAL FOR THE TREATMENT OF HIGH GRADE GLIOMAS (HGG) IN CHILDREN2. EVALUATION OF DIGOXIN FOR RELAPSED NON-WNT, NON-SHH MEDULLOBLASTOMA (IN DEVELOPMENT) THIS TRIAL WILL EVALUATE THE EFFICACY OF DIGOXIN IN TREATING PATIENTS WITH RELAPSED NON-SHH, NON-WNT MEDULLOBLASTOMA.NON TREATMENT TRIALS1. ROLE OF MYELOID-DERIVED SUPPRESSOR CELLS (MDSC) IN THE DEVELOPMENT OF IMMUNE TOLERANCE AFTER ALLOGENIC HEMATOPOIETIC CELL TRANSPLANTATION (ALLOHCT) -THIS IS AN OBSERVATIONAL TRIAL WITH GOAL OF BETTER UNDERSTANDING THE PROCESS OF DEVELOPING IMMUNE TOLERANCE AFTER BLOOD AND MARROW TRANSPLANTATION (BMT). 2. BLOOD BASED BIOMARKERS FOR MINIMAL RESIDUAL DISEASE DETECTION IN PEDIATRIC SARCOMAS - THE PURPOSE OF THIS STUDY IS TO SEE IF DETECTING CELL-FREE PLASMA TUMOR DNA (PTDNA) AND CIRCULATING TUMOR CELLS (CTC) CAN PREDICT RECURRENCE OF DISEASE IN PATIENTS WHO ARE IN RADIOGRAPHIC REMISSION 2-3 WEEKS AFTER TREATMENT. PLASMA TUMOR DNA (PTDNA) IS FREE FLOATING DNA FROM THE TUMOR FOUND IN THE BLOOD STREAM AND CIRCULATING TUMOR CELLS3. PEDIATRIC TOTAL CANCER CARE- THIS TRIAL FOCUSES ON TISSUE AND BLOOD COLLECTION TO FURTHER PERSONALIZED MEDICINE FOR CHILDREN WITH CANCERTISSUE SAMPLE STUDIES1. COMPREHENSIVE MOLECULAR PROFILING OF RARE PEDIATRIC AND AYA CANCERS - DEVELOPMENT OF AN INFRASTRUCTURE, METHODS, AND STANDARD OPERATING PROCEDURE TO COLLECT AND PROCURE HISTOLOGY SPECIFIC (ESTHESIONEUROBLASTOM AND EMBRYONAL SARCOMA) TISSUE RESOURCES AVAILABLE THROUGHOUT THE SUNSHINE PROJECT AND ASSOCIATED REPOSITORIES. CHART REVIEW STUDY1. COMPREHENSIVE GENETIC PROFILING FOR PEDIATRIC MALIGNANCIESONGOING PRE-CLINICAL TRIALS1. ASSESSMENT OF EXPANDED TUMOR INFILTRATING NK-CELLS COLLABORATIVE2. DEVELOPMENT OF PERSONALIZED RNA LOADED NANOPARTICLES3. FUSION PROTEINS BY IMMUNOTHERAPYSUNSHINE PROJECT LABORATORYTHE SUNSHINE LAB CONTINUES WITH THE IMPORTANT TASK OF FINDING PROMISING NEW TREATMENT REGIMENS FOR SARCOMAS, AMONG THE MOST DEADLY PEDIATRIC CANCER. DURING THIS PAST YEAR, THE SUNSHINE LAB HAS BUILT ON COMBINATION DRUG SCREENING PLATFORM AND FOCUSED ON OSTEOSARCOMA AND EWING SARCOMA.PEDIATRIC SARCOMAS OFTEN SHRINK OR GO AWAY WITH INITIAL THERAPY BUT THEN LATER RELAPSE AND ARE THEN MUCH MORE DIFFICULT TO CURE. THIS SUGGESTS THAT A SMALL AMOUNT OF DISEASE ELUDES CURRENT THERAPY. WE CONSIDER THIS SMALL, RESISTANT POPULATION SHOULD BE THE FOCUS OF PRECLINICAL RESEARCH AND HAVE 3 MAJOR PROJECTS RESULTING FROM THAT UNDERSTANDING OF PEDIATRIC SARCOMA. 1. WE HAVE DEVELOPED A MODEL OF THESE TWO COMPETING POPULATIONS, TERMED HETEROGENEITY, TO FIGURE OUT THE BEST STRATEGY TO ELIMINATE BOTH CANCER CELL POPULATIONS WITH TIMING AND COMBINATIONS OF THERAPIES. 2. IN COLLABORATION, WE ARE INVESTIGATING "SECOND STRIKES" IN BOTH OSTEOSARCOMA AND EWING SARCOMA. SECOND STRIKES ARE THERAPIES AFTER THE DISEASE HAS SHRUNK WITH INITIAL THERAPY. RATHER THAN SHRINK THE TUMOR, WE ARE INVESTIGATING THERAPIES TO ELIMINATE THE RESIDUAL CELLS BETTER THAN CONTINUING THE INITIAL THERAPY (FIRST STRIKE). THIS RESULTED FROM THE SUNSHINE LAB PARTICIPATING IN THE 9TH ANNUAL INTEGRATED MATHEMATICAL ONCOLOGY WORKSHOP AT MOFFITT CANCER CENTER. 3. IN COLLABORATION, WE HAVE FOCUSED ON A NEW, NON-MUTATED TARGET IN OSTEOSARCOMA, THE CMG HELICASE. WE HAVE BOTH IDENTIFIED THIS AS A WEAKNESS IN CANCER CELLS MORE THAN NORMAL CELLS AND IDENTIFIED A DRUG CLASS THAT HOLDS PROMISE AS AN EVENTUAL THERAPY. WE ARE EXPLORING THIS AGENT ALONE AND IN COMBINATION TO MAXIMIZE THE CHANCE FOR A SUCCESSFUL CLINICAL TRIAL. 4. IN COLLABORATION, WE ARE BUILDING ON PRIOR PUBLICATIONS SHOW ACTIVITY OF EPIGENETIC DRUGS LIKE PANOBINOSTAT AND EXPLORING MECHANISMS TO ENHANCE THIS THERAPY IN OSTEOSARCOMA. 5. IN COLLABORATION, WE ARE INVESTIGATING AN UNDERAPPRECIATED DNA REPAIR ENZYME AS AN ACHILLES HEEL IN EWING SARCOMA CALLED PARP16.