INCTR

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Clinical Research Program

• 2003 2004
• Melissa Adde

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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

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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

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Strategy Groups

• African Burkitts Lymphoma
• Breast Cancer
• Cervical Cancer
• Leukemia
• Leukemia Study Group of India
• Lymphoma
• Osteosarcoma
• Retinoblastoma

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

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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 wasnt built in a day!

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Strategy Groups

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

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The Treatment and Characterization of Burkitts
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

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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 lt 10
  cm)
• High risk arm (all other patients)
• Second-Line Treatment
• Failures of First-Line Treatment

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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)

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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)

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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

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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

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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

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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

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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

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

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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

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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

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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)

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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 childs age and
  stage
• To determine if factors arise from parents,
  demographics or other aspects of primary health
  care.

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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)

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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

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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 fathers
  education level
• Time interval between first symptom and diagnosis
  was associated with fathers education level

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Projects in Development - 1

• African Burkitts 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

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Projects in Development - 2

• Cervical Cancer
• Treatment of Early Stage Cervical Cancer
• Treatment of Locally Advanced Cervical Cancer
• Expanding Coverage of Screening Programs

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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

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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

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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

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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

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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)
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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)

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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

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Thank
You!