NATIONAL PEDIATRIC CANCER FOUNDATION INC

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 ADULTS - THIS 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 OSTEOSARCOMA. HIS TRIAL WILL DETERMINE IF THE COMBINATION OF AZACITIDINE AND NIVOLUMAB CAN IMPROVE EVENT FREE SURVIVAL OVER THE 20% HISTORICAL CONTROL USED FOR RECURRENT OSTEOSARCOMA STUDIES IN THE CHILDREN'S ONCOLOGY GROUP.3. EVOLUTIONARY INSPIRED THERAPY FOR NEWLY DIAGNOSED, METASTATIC, FUSION POSITIVE RHABDOMYOSARCOMA - METASTATIC, 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. ACTION TRIAL: ADOPTIVE CELLULAR THERAPY FOLLOWING DOSE-INTENSIFIED TEMOZOLOMIDE IN NEWLY-DIAGNOSED PEDIATRIC HIGH-GRADE GLIOMAS (PHASE I) - THIS IMMUNOTHERAPY TRIAL WILL EXPLORE THE SAFETY OF ADOPTIVE CELLULAR THERAPY IN PEDIATRIC PATIENTS WITH HIGH GRADE GLIOMAS (HGG) WHO HAS RECEIVED DOSE INTENSIFIED TEMOZOLOMIDE AND DENDTRIC CELL (DC) + AUTOLOGOUS LYMPHOCYTE TRANSFER (XALT) WITH AND WITHOUT AUTOLOGOUS HEMATOPOETIC STEM CELLS (HSCS). WE WILL ALSO BE EXAMINING FEASIBILITY OF ALL ENROLLED PATIENTS COMPLETING TREATMENT AND ANALYZING PROGRESSION FREE SURVIVAL AND OVERALL SURVIVAL AFTER THIS TREATMENT. 5. 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 CELLS.6. 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: THE TINKS TRIAL - THE PURPOSE OF THIS TRIAL IS TO DETERMINE THE SAFETY OF THE ADDITION OF ADOPTIVE TRANSFER OF UNIVERSAL DONOR, TGFB IMPRINTED (TGFBI), EXPANDED NK CELLS TO GEMCITABINE/DOCETAXEL (GEM/DOX) FOR TREATMENT OF RELAPSED AND REFRACTORY SARCOMAS AND TO DETERMINE THE 6 MONTH PROGRESSION FREE SURVIVAL ACHIEVED WTIH THIS TREATMENT.7. FEASIBILITY OF GENERATING NOVEL TRANSLATIONAL AND THERAPEUTIC STRATEGIES BASED ON A MULTICENTER, PEDIATRIC AND AYA EVOLUTIONARY TUMOR BOARD (PEDSETB) - PEDIATRIC EVOLUTIONARY TUMOR BOARD (PEDSETB) IS A MULTIDISCIPLINARY FORUM TO APPROACH AN INDIVIDUAL PATIENT'S CANCER AND PROPOSE ADDITIONAL IDEAS FOR CARE. THE PEDSETB WILL GATHER TOGETHER DISCIPLINES NOT OFTEN ENGAGED IN CANCER WORK AND USE INSIGHTS FROM EVOLUTION TO OPTIMALLY MODEL, RESEARCH, AND IMPACT PEDIATRIC CANCER OUTCOMES. STRATEGIES FROM PEDSETB'S PREDECESSOR HAVE BEEN INSTRUMENTAL IN THE DESIGN OF SEVERAL OF NPCF'S MOST RECENT CLINICAL TRIALS8. EVALUATION OF DIGOXIN FOR RELAPSED NON-WNT, NON-SHH MEDULLOBLASTOMA (PHASE 2 STUDY) - THIS TRIAL WILL EVALUATE THE EFFICACY OF DIGOXIN IN TREATING PATIENTS WITH RELAPSED NON-SHH, NON-WNT MEDULLOBLASTOMA AND TO DETERIMINE IF DIGOXIN IMPROVES PROGRESSION FREE SURVIVIAL AT 4 MONTHS AFTER INITATION OF STUDY TREATMENT IN THIS PATIENT POPULATION. 9. METASTATIC EWING'S TRIAL TESTING SCHEDULE ENHANCEMENT TO IMPROVE OUTCOMES - THIS TRIAL WILL TEST OUR ABILITY TO ADMINISTER FREQUENTLY CHANGING CHEMOTHERAPY REGIMENS, CALLED SEQUENTIAL SECOND STRIKES, TO PATIENTS WITH WIDELY METASTATIC EWING SARCOMA TO STOP ITS DEVELOPMENT OF RESISTANCE TO CHEMOTHERAPY AND IMPROVE CURE RATES.SUNSHINE PROJECT LABORATORY THE SUNSHINE LAB CONTINUES WITH THE IMPORTANT TASK OF FINDING PROMISINGNEW 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.