Clinical Research Program: Clinical Research Program 2003 – 2004 Melissa Adde


Major Functions: Major Functions Coordination of Strategy Groups Management of Clinical Research Studies Administration of INCTR Ethical Review Committee Provision of Data Management Services Education and Training


Strategy Groups: Strategy Groups Comprised of investigators from developing countries Disease-specific Determine role of the group/INCTR in the control of a specific cancer Promote public and professional education


Strategy Groups: Strategy Groups African Burkitt’s Lymphoma Breast Cancer Cervical Cancer Leukemia Leukemia Study Group of India Lymphoma Osteosarcoma Retinoblastoma


Slide5: Leukemia (India) Breast Cancer Lymphoma (African BL) Retinoblastoma Strategy Groups Keukenhof


Strategy Group Meetings: Strategy Group Meetings African BL, Aug 2004 (Tanzania) Breast Cancer October, 2003 (Egypt) May, 2004 (Brussels) Cervical Cancer, Aug 2004 (Brussels) Leukemia/Leukemia Study Group of India Feb, 2004 (India) July, 2004 (videoconference) Lymphoma, Oct 2003 (Egypt) Retinoblastoma, April, 2004 (Brussels)


Translation in Actions: Translation in Actions 5 On-going Projects (not including palliative care, IARC project, Lilly study) 8 Projects – proposed or in development Remember More than simply “willingness” to collaborate Commitment to work together to develop projects Takes time – Rome wasn’t built in a day!


Strategy Groups: Strategy Groups On-going activities will be presented and followed by discussion in Session 8 Specific presentations will be given for: African Burkitt’s Lymphoma (M. Durosinmi) Breast Cancer (Z. Aziz) Cervical Cancer (C. Santos) Leukemia Study Group of India (S. Advani) Retinoblastoma (S. Epelman)


The Treatment and Characterization of Burkitt’s Lymphoma (BL) in Africa: The Treatment and Characterization of Burkitt’s Lymphoma (BL) in Africa Primary Objectives Characterize presentation features Assess response, EFS, DFS and OS Characterize pattern of CNS disease and relapse Assess toxicities Secondary Objectives Characterize pattern of gene expression Assess serum EBV DNA levels


The Treatment and Characterization of BL in Africa: The Treatment and Characterization of BL in Africa First-Line Treatment Newly diagnosed, previously untreated patients Two treatment arms Low risk arm (single extra abdominal mass < 10 cm) High risk arm (all other patients) Second-Line Treatment Failures of First-Line Treatment


The Treatment and Characterization of BL in Africa: The Treatment and Characterization of BL in Africa 5 participating institutions in 4 countries Kenya, Nigeria (2), Tanzania, Uganda INCTR ERC approval July, 2003 Local ethical approval in 4 of 5 participating institutions Patient accrual began in August, 2004 Enrolled: 3 Not entered: 1 (not eligible – history prior chemo)


Retrospective Survey of Presentation Features of Breast Cancer and Risk Factors for Treatment Outcome: Retrospective Survey of Presentation Features of Breast Cancer and Risk Factors for Treatment Outcome Objectives Quantify total number of breast cancer patients evaluated Define history and presentation features of breast cancer Define frequency of risk factors for treatment outcome (diagnosis, stage, treatment)


Retrospective Survey of Presentation Features of Breast Cancer and Risk Factors for Treatment Outcome: Retrospective Survey of Presentation Features of Breast Cancer and Risk Factors for Treatment Outcome Objectives (continued) Estimate the response, DFS and OS Assess frequency of risk factors known to be relevant in western populations Correlate risk factors for treatment outcome with response, DFS and OS


Retrospective Survey of Presentation Features of Breast Cancer and Risk Factors for Treatment Outcome: Retrospective Survey of Presentation Features of Breast Cancer and Risk Factors for Treatment Outcome Participating institutions in 9 countries Latin America – Argentina, Mexico and Peru Africa – Tanzania Middle East – Egypt, Kuwait South Asia – Pakistan, India and Nepal Initiate in 4 centers, then expand to others


Retrospective Survey of Presentation Features of Breast Cancer and Risk Factors for Treatment Outcome: Retrospective Survey of Presentation Features of Breast Cancer and Risk Factors for Treatment Outcome INCTR ERC approval July, 2003 Local approval in 8 of 9 participating institutions Initiated in June, 2004 Cancer Institute, Chennai, India


Phase II Study of Previously Untreated Metastatic Osteosarcoma with a Combination of Chemotherapy and Surgery: Phase II Study of Previously Untreated Metastatic Osteosarcoma with a Combination of Chemotherapy and Surgery Short duration protocol (25 weeks) Alternating cycles of 2 chemotherapy regimens every 3 weeks Neoadjuvant and Adjuvant Surgical resection of primary, Week 12 Surgical resection of metastatic disease, Week 17


Phase II Study of Previously Untreated Metastatic Osteosarcoma: Phase II Study of Previously Untreated Metastatic Osteosarcoma Problem: Rate of accrual lower than anticipated rate Observed vs “assumed” rate of accrual PI leaving participating institution Surgeons declined to participate Inability to perform limb-sparing procedures Competing group/institutional protocols


Phase II Study of Previously Untreated Metastatic Osteosarcoma: Phase II Study of Previously Untreated Metastatic Osteosarcoma


Phase II Study of Previously Untreated Metastatic Osteosarcoma: Phase II Study of Previously Untreated Metastatic Osteosarcoma


The Treatment and Characterization of ALL in Children, Adolescents and Young Adults: The Treatment and Characterization of ALL in Children, Adolescents and Young Adults Primary Objectives Characterize pattern of ALL in India (immunophenotype, DNA index, molecular profiling) Correlate lab characteristics with clinical characteristics Attempt to identify prognostic factors predictive of relapse, EFS, DFS and OS


The Treatment and Characterization of ALL: The Treatment and Characterization of ALL Secondary Objectives To assess acute toxicity of planned therapy To collect baseline and post-treatment assessments of neuropsychological function for future studies of late CNS toxicity


The Treatment and Characterization of ALL: The Treatment and Characterization of ALL Protocol approved by INCTR ERC, January, 2003 Protocol approved by ICMR, May, 2004 Protocol approved locally in 3 of 4 participating institutions Implementation Meeting, July, 2004 Patient accrual began Aug 1, 2004


The Treatment and Characterization of ALL: The Treatment and Characterization of ALL Total Number of Patients Entered: 13 Males/Females: 10/3 Age Range: 1 – 22 years Total Number Not Enrolled: 1 (ineligible, prior treatment)


Understanding Problems Faced by Parents of Children with Retinoblastoma (RB) Prior to Treatment: Understanding Problems Faced by Parents of Children with Retinoblastoma (RB) Prior to Treatment Objectives To determine association between stage and time interval between first symptom, date of diagnosis and date of first treatment To identify factors influencing time interval To determine association between child’s age and stage To determine if factors arise from parents, demographics or other aspects of primary health care.


Understanding Problems Faced by Parents of Children with RB Prior to Treatment: Understanding Problems Faced by Parents of Children with RB Prior to Treatment Participating Institutions: 15 Contributing Institutions: 10 India (3) Turkey (2) Brazil (1) Mexico (1) Nigeria (1) Pakistan (1) Zimbabwe (1)


Understanding Problems Faced by Parents of Children with RB Prior to Treatment: Understanding Problems Faced by Parents of Children with RB Prior to Treatment Initiated in 2001 Experience with survey gained Positively received by parents/guardians of children Questionnaire and Clinical Data Form recently modified 289 surveys recently analyzed


Understanding Problems Faced by Parents of Children with RB Prior to Treatment: Understanding Problems Faced by Parents of Children with RB Prior to Treatment Important Findings to Date Older children have higher stages of disease Strong association of higher stages in children from rural communities Strong association of stage with father’s education level Time interval between first symptom and diagnosis was associated with father’s education level


Projects in Development - 1: Projects in Development - 1 African Burkitt’s Lymphoma Treatment of Lymphomatous Meningitis with Liposomal ARAC Phase I/II Study of Prozac in Relapse Patients Breast Cancer Randomized Trial Comparing Three Treatment Approaches for Stage III Breast Cancer


Projects in Development - 2: Projects in Development - 2 Cervical Cancer Treatment of Early Stage Cervical Cancer Treatment of Locally Advanced Cervical Cancer Expanding Coverage of Screening Programs


Projects in Development - 3: Projects in Development - 3 Lymphoma Randomized trial to evaluate the use of CHOP vs CHOP + anti-CD20 in newly diagnosed patients with Diffuse Large B Cell Lymphoma Retinoblastoma Treatment of Extraocular Retinoblastoma


Data Management of Research Studies: Data Management of Research Studies Design and Development of Study-Specific Databases Retinoblastoma Survey Study African BL Protocol Leukemia Protocol Approaches Used INCTR or participating institutions perform data entry Stand alone applications vs internet based


Data Quality Assurance Plans: Data Quality Assurance Plans Study-specific SOPs data entry, queries, updates, manuals Functions Incorporated into Databases CRF tracking (submitted, overdue, “cleaned”) Basic “business” rules to minimize entry errors Minimum checks (missing or out of range values) Extensive checks (internal consistency of data) Listings Query generation and tracking Audit trails


Data Management: Data Management Study Specific Monitoring Plans Data monitors appointed for certain studies Independent pathology reviews Periodic visits to sites for auditing purposes (using INCTR personnel or expert volunteers) Creation of study committees (local investigators) Assignment of responsibilities of study committees


Provision of Data Management Services: Provision of Data Management Services Within scope of INCTR mission Relates to an important cancer in developing countries Patient accrual completed (516 patients) Phase III randomized comparison of Gemcitabine, Cisplatin and Radiation followed by Adjuvant Gemcitabine and Cisplatin vs Concurrent Cisplatin and Radiation in Cancer of the Cervix (Stages IIB to IVA)


Education and Training: Education and Training Protocol Implementation Meetings Leukemia Study – July, 2004 African BL Study – August, 2004 Clinical Trials Workshop, Brazil, Sept, 2004 “Basic Data Management” Workshop Data Managers/Monitor Training for Leukemia Study (November, 2004) In-depth review of protocol, CRFs, study procedures with practical experience (e.g., toxicity grading)


Special Thank You: Special Thank You Dr David Venzon, Biostatistician,NCI Mr Paul Jarosinski, Pharmacist, NIH Martha Flores-Rojo, Instituto Nacional de Pediatria, Mexico INCTR Ethical Review Committee Panel of External Scientific Reviewers Capitol Technology Information Services (CTIS) Staff of Clinical Trials Office


Slide37: Thank You!