PhUSE                         Lisbon, Portugal – 8-10 October 2007                         Web-Triage                     ...
SENDO (Southern Europe New Drug Organisation) Non profit Academic Research Organisation (ARO) Early Drug Development in On...
SENDO (Southern Europe New Drug Organisation) - Partners                                    HQ-Activities                 ...
Drug Development Process – Study Phases                 Classic Clinical Development  Phase I               Phase II      ...
Phase I Dose Escalation studies in Oncology  Conducted in humans  Conducted in cancer patients      Usually with advanced ...
Examples of Dose Limiting Toxicities (DLT)  Drug Related Toxicities, such as    Absolute granulocyte count <0.5 x10^9/L la...
Example of a Dose Escalation Protocol Dose level          Dose                   Dose  (cohort)         increment         ...
Ethical Issues in Phase I in Oncology  Maximising patients exposure to potentially  therapeutic doses  Minimising patients...
Accrual Issues in Phase I in Oncology  Better selection of patients  Appropriate education of referring physicians  Apply ...
Patient TriageThe french word ‘triage’ means ‘picking out’ (sorting)and it was used in World War I, when a ‘system’ wasado...
The Web-Triage Application: User Requirements Defining Study Characteristics    Dose Levels    Data to be Collected, inclu...
The Web-Triage Application: Take a tour (1)  Study Information: The Dose Levels          Tinazzi A Cattaneo A Ferraresi L ...
The Web-Triage Application: Take a tour (2)  Investigator Login: List of enabled open Trials          Tinazzi A Cattaneo A...
The Web-Triage Application: Take a tour (3)  The Investigator Propose a Candidate  The first dose-escalation (7.5+40), is ...
The Web-Triage Application: Take a tour (3)  Data-entry functionality                      Prior Chemotherapy             ...
The Web-Triage Application: Take a tour (4)  Study Project Manager Reviews the Study Status  The candidate is eligible and...
Automatic Communication Via email     Once a candidate is proposed (from Inv      HQ)     Once a candidate is accepted/rej...
The Web-Triage Application: System Design ASP.NET  unified software development model that includes the  services necessar...
The Web-Triage Application: N-Tier Concept  N-Tier System                                               A Client-Server Ar...
Triage Network Architecture         Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Reg...
The Web-Triage Application: Technical References  HTTP://MSDN2.MICROSOFT.COM/EN-  US/LIBRARY/MS973279.ASPX  HTTP://WWW.MIC...
Conclusions Conducting phase I oncology studies has major potential pitfalls Fast accrual is required in phase I oncology ...
Questions        Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase ...
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Web-Triage An Application for patient registration in phase I dose escalation studies

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Web-Triage An Application for patient registration in phase I dose escalation studies

  1. 1. PhUSE Lisbon, Portugal – 8-10 October 2007 Web-Triage An Application for patient registration in phase I doseEarly Drug Development escalation studies In Oncology Microsoft Tools Stream (MT02) Angelo Tinazzi Data Management and Programming Unit SENDO Tech S.r.l. – Milan (ITALY) co-authors Alessandro Cattaneo SENDO Tech S.r.l. Paolo Ferroni, Lucio Ferraresi Eventi Telematici – Milan (ITALY)
  2. 2. SENDO (Southern Europe New Drug Organisation) Non profit Academic Research Organisation (ARO) Early Drug Development in Oncology Coordinating a Network of oncology-hospitals 5 phase I (2 in Italy, 3 in Switzerland) ~ 30 phase II (Italy, Switzerland, Spain) Pre-clinical Laboratory (PK, PD) Head Quarter based in Milan Clinical Development Clinical Operations Data-Management Biostatistics Medical Writing Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 2 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  3. 3. SENDO (Southern Europe New Drug Organisation) - Partners HQ-Activities Core activities Clinical developmentIOSI, Bellinzona, Head quarters Trial design Clinical Operation INT, Milano Luca Gianni Cristiana Sessa Selected Milano & MoA Screening Data Center 12 ViaClinicalModrone, Visconti di trials Regulatory 18 people Pharmacokinetics Monitoring Pharmacodynamics Logistic IEO, Milan HGVdH Barcelona Filippo deBraud Josè Baselga and also .... CHUV Lausanne, KSSG S Gallen, Istituto Mario Negri Milano Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 3 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  4. 4. Drug Development Process – Study Phases Classic Clinical Development Phase I Phase II Phase III Phase IV Tolerability Activity Efficacy Surveillance Approval FDA/EMEA/… Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 4 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  5. 5. Phase I Dose Escalation studies in Oncology Conducted in humans Conducted in cancer patients Usually with advanced disease Failing previous ‘standard’ therapies Good Performance Status Dose escalation Pre-defined dose-levels (Fibonacci series) The starting dose is usually 1/10 the median lethal dose in mouse or other animals (LD10) Maximum Tolerated Dose (MTD), the dose where 2/3 or 2/6 DLTs are experienced Recommended Dose (RD), the dose before MTD where no more than 1/6 DLTs are experienced Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 5 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  6. 6. Examples of Dose Limiting Toxicities (DLT) Drug Related Toxicities, such as Absolute granulocyte count <0.5 x10^9/L lasting >= 5 days Platelets <50 x10^9/L Failure to deliver therapy in day 8 due to drug related toxicity Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 6 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  7. 7. Example of a Dose Escalation Protocol Dose level Dose Dose (cohort) increment (mg/m2) 1 1 2 3 Starting dose 0.10 2 4 5 6 7 8 9 100% 0.20 3 10 11 12 17 18 19 RD 67% 0.33 4 13 14 15 16 17 … 50% 0.50 MTD 5 33% 0.67 6 33% 0.89 7 33% 1.18 8 33% 1.57 9 33% 2.08x1 x2 x3 Patient Cohort (patient nr. x1, x2, x3, …) Dose Limiting Toxicities Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 7 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  8. 8. Ethical Issues in Phase I in Oncology Maximising patients exposure to potentially therapeutic doses Minimising patients treated at ineffective doses Minimising patients treated at toxic doses Historically low probability of response in phase I trials Unknown toxicity and benefit of new agent Informed Consent Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 8 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  9. 9. Accrual Issues in Phase I in Oncology Better selection of patients Appropriate education of referring physicians Apply fewer restrictions in eligibility criteria The window of opportunity of starting a phase I trial may be limited because the clinical course of these end-stage patients is unpredictable No more than 2-3 investigator sites per trial Concurrent trials Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 9 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  10. 10. Patient TriageThe french word ‘triage’ means ‘picking out’ (sorting)and it was used in World War I, when a ‘system’ wasadopted for the sorting of wounded soldiers intospecific groups requiring differential medicalinterventions according to the severity of their injuries …a similar approach is used in emergency unit unit to ration limited medical resources and in Phase I studies in oncology…..In phase I trials, patients have to be selected as soonas possible so that investigators can be prepared totreat a new patient Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 10 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  11. 11. The Web-Triage Application: User Requirements Defining Study Characteristics Dose Levels Data to be Collected, including pre-registration data Library for Study items (i.e. chemotherapy regimens) Opening or Close dose-levels according to dose- escalation rules Manage concurrent dose-escalation trials The Investigators can review study status (dose-level cohorts) and propose candidates The Study Project Managers need to be alerted as soon as a candidate is proposed Review and approve|reject patient candidate Manage dose-levels (close, open and re-open) Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 11 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  12. 12. The Web-Triage Application: Take a tour (1) Study Information: The Dose Levels Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 12 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  13. 13. The Web-Triage Application: Take a tour (2) Investigator Login: List of enabled open Trials Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 13 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  14. 14. The Web-Triage Application: Take a tour (3) The Investigator Propose a Candidate The first dose-escalation (7.5+40), is going to be closed, no DLT criteria reached The 15+40 Opened dose-level, has slots available EPTD, it is the planned administration starting date for next patients Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 14 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  15. 15. The Web-Triage Application: Take a tour (3) Data-entry functionality Prior Chemotherapy Dictionary Online Data Validation Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 15 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  16. 16. The Web-Triage Application: Take a tour (4) Study Project Manager Reviews the Study Status The candidate is eligible and accepted for registration The candidate is not fully eligible and accepted for registration The candidate is not eligible and not suitable for study registration Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 16 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  17. 17. Automatic Communication Via email Once a candidate is proposed (from Inv HQ) Once a candidate is accepted/rejected (from HQ Inv) Once a candidate is confirmed for registration (from HQ Inv) Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 17 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  18. 18. The Web-Triage Application: System Design ASP.NET unified software development model that includes the services necessary to build enterprise-class Web applications MS SQL Server 2005 IIS (version 6.0) Web Server HTTPS SSL 128/256 bit for data-encryption Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 18 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  19. 19. The Web-Triage Application: N-Tier Concept N-Tier System A Client-Server Architecture, where each module is developed separately Presentation Layer Workflow Layer Business Rule Layer Data Layer Data Store Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 19 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  20. 20. Triage Network Architecture Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 20 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  21. 21. The Web-Triage Application: Technical References HTTP://MSDN2.MICROSOFT.COM/EN- US/LIBRARY/MS973279.ASPX HTTP://WWW.MICROSOFT.COM/BELUX/MSDN/NL/ COMMUNITY/COLUMNS/HYATT/NTIER1.MSPX HTTP://MSDN2.MICROSOFT.COM/IT- IT/NETFRAMEWORK/DEFAULT.ASPX Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 21 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  22. 22. Conclusions Conducting phase I oncology studies has major potential pitfalls Fast accrual is required in phase I oncology studies for both ethical and economical issues The Accrual is a crucial step in succeeding and a tool such as Web-Triage may improve timeline and quality Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 22 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
  23. 23. Questions Tinazzi A Cattaneo A Ferraresi L Ferroni P WEB-Triage: an applicaition for patient Registration in Phase I 23 dose-escalation studies PhUSE 2007, MT02 (Lisbon, Portugal – 8-10 October 2007)
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