Experience of a Pediatric Oncology Clinical Research Center in Brazil. Antonio Sergio Petrilli, MD, PhD

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1 Experience of a Pediatric Oncology Clinical Research Center in Brazil Antonio Sergio Petrilli, MD, PhD

2 Children and adolescents Heterogeneous in many aspects 38% of Brazilian population (IBGE, 2000) 11,530 new cases of cancer/year (<20 years) (INCA, 2012)

3 Clinical Research in Pediatric Oncology - Challenges Too few kids Unlicensed and off label drug use over 50 % of the medicines used for children had not been tested for use in this age group since 2008: more than 600 pediatric investigation plans have been approved Develop cooperative groups Training human resources Funding Improve regulatory environment PROGRESS REPORT ON THE PAEDIATRIC MEDICINE REGULATION 2007 (2013) Average time to approval (IOP-GRAACC/UNIFESP, Brazil): 8-16m Boklan, Mol Cancer Ther, 2006 Conroy, Annals of Oncology, 2003

4 Clinical Research in Pediatric Oncology - Challenges Promote collaboration between industry, academia and government Academy: fostering research, publications Industry: reduce drug lag,strengthen pipelines,generates spill over effect Government: economic benefit,setting of global level standard Only 10% of 15-to-19 year old adolescent cancer patients are entered into trials, compared to 60% of those under the age of 15 (NCI, 2008)

5 Mortality rate reduction Epidemiology Mortality Rate Reduction U.S.A % 2.8% 2.6% Média Anual em % 2% 1% Why? 1.8% 1.5% 0.9% 1.1% 1.5% 0.4% 0% Age (year) Idade (Anos) Bleyer, W.A. The impact of childhood cancer on the United States and the world Ca,40: ,1990; Bleyer, W.A th ASCO 2000 Conference

6 Participation in Clinical trials Epidemiology Enrollment in NCI-Sponsored Trials ( ) Idade (Anos) Age (year) Bleyer, W.A. The impact of childhood cancer on the United States and the world Ca,40: ,1990; Bleyer, W.A th ASCO 2000 Conference

7 Mortality rate reduction Mortality rate reduction Participation in Clinical trials Epidemiology Rate of participation in U.S. clinical trials and mortality ( ) 25% 3% 20% 15% % 2% 5% 0% r =.91, p =.001 1,000 10,000 Participation in CT (log) % % Age (year) Bleyer, W.A. The impact of childhood cancer on the United States and the world Ca,40: ,1990; Bleyer, W.A th ASCO 2000 Conference

8 Clinical Research in Pediatric Oncology - Successes 5 year survival ~ 80% (SEER 2010) Parents supported by medical staff are highly motivated to enroll their kids on CT Response assessment easier in kids Development of Clinical Trials in a Cooperative Group Setting Boklan, Mol Cancer Ther,

9 IOP-GRAACC/UNIFESP - Clinical Research Department Well-trained infrastructure: Dedicated medical personnel Study coordinators, nurse and pharmacist Data manager, statistical support Electronic data capture for institutional protocols Full regulatory support Archiving facilities

10 IOP-GRAACC/UNIFESP - Studies Year # Institutional # Sponsored # Participants Total Average Accrual studies ongoing Study A Study B Study C Study D Study E Study F Commited Included Feasibilities 7/13 (53%) 5/11 (45%) 1/9 (11%) 10

11 IOP-GRAACC/UNIFESP-Multicenter Clinical Trials COG clinical trials: adrenocortical carcinoma, hepatoblastoma, retinoblastoma Drug development industry sponsored clinical trials (II-IV) Global Databases: Center for International Blood and Marrow Transplant Research (CIBMTR) Paediatric Fungal Network (PFN) Investigator Initiated Trials (IITs): CNS and bone tumors, infectology

12 IOP-GRAACC/UNIFESP - Translational Research Genetic and Molecular Biology Laboratory Investigation of tumor markers and therapeutic targets Tissue Bank Consortium Tests in OS cell lines Tumor Patients Samples BST CNS Leukemia Neuroblastic Wilms Lymphoma GCT Liver Retinoblastoma 5 12 Langerhans 7 18 Melanoma 2 9 Miscelanea Total

13 Cutting edge research Clinical Research Genetics and Genomics Clinical data Adams, J.U, Building the bridge from bench to bedside, Nature Reviews Drug Discovery, June 2008

14 Brazilian Osteosarcoma Treatment Group (BOTG) Created in 1980 s 5 consecutive studies completed Beginning: small number of patients enrolled few specialized institutions in a single city (SP) Study V: 25 institutions from 9 states and 15 different cities 368 patients enrolled

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16 At present Latin American Group of Osteosarcoma Treatment Multicentric, randomized study with data collection over 32 sites in Latin America Self-maintained Generate information on lower cost treatments

17 Latin American Group of Osteosarcoma Treatment Objectives: Evaluate if HD-MTX, CDDP and Doxorubin will improve EFS of patients with resectable osteosarcoma Investigate the impact of metronomic treatment on EFS of non-metastatic and metastatic osteosarcoma patients

18 Osteosarcoma 2006 Protocol Non Metastatic

19 Osteosarcoma 2006 Protocol Non Metastatic

20 Osteosarcoma 2006 Protocol Metastatic

21 Overall survival N=655 A) - Non Metastatic Arm 1 (no metronomic) B) - Non Metastatic Arm 2 (with metronomic) C) Metastatic (with metronomic) D) Non Metastatic (no randomization) E) Metastatic (no metronomic) 2y 5y n A B C D E

22 Value of a shared protocol OS outcomes in 2 centers Relapse Refusal Progression Toxic death Refusal Relapse Toxic death Progression Center 1 Center 2

23 Childhood Cancer Survival 90 High-income vs. low middle-income countries Survival gap High-income countries Low middle-income countries

24 At IOP-GRAACC/UNIFESP Survival gap closing in GRAACC, Brazil Survival gap High-income countries IOP/GRAACC-UNIFESP Low middle-income countries

25 Our contacts Coordinating Site Prof. Dr. Antonio Sérgio Petrilli Dra. Andreza A. Senerchia Arnaldo Pires Mariane Diniz Raquel Passos Thais Rodrigues Tel: Fax : sergiopetrilli@graacc.org.br