INCA Initiatives on Innovative Drugs in Cancers

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					  INCa Initiatives on Innovative Drugs in Cancer

1) Introduction : - What is the INCa ?
                  - The French National Cancer Plan

2) French centres accreditation for Early phases clinical trials (CLIP²)

3) Collaboration NCI-INCa on early phases clinical trials.

4) Conclusion/ Next steps                   Christian Cailliot,
                                            Responsible for early phases clinical trials,
                                            Research Department.
                                            Institut National du Cancer (French NCI)
                              INCa :
               « Public National Agency in Cancer »
                        (Similar to US NCI)

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               Inca’s Initiatives on Early phases is part of the
                  Second National Cancer Plan 2009- 2013

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                               5 DOMAINS of ACTIONS

               - RESEARCH
               To insure and stimulate translation of research to cancer care

               - OBSERVATION
               To insure a better knowledge of cancer reality

               To prevent to avoid cancer and/or limit their severity

               - CARE
               To warrant to each patient a « personnalized » and efficient care

               To improve quality of life during and after active disease; fighting
               against any form of exclusion due to cancer

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      3 Transversal Themes (in each domain) aimed to :

  - A better analysis and dedicated actions to fight inequities

  - Stimulate the analysis and the management of risk factors of cancers
    linked to individual and environmental factors

  -Re-inforce the role of GPs and home care to insure a better quality of
   life during and after cancer therapy

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                            Focus on Early Phases and International

               Mesure 1

               Action 1.3 : Structure and stimulate research in the early phases of
               new anti-cancer drug clinical trials.

               Action 1.4 : Establish research and development partnerships in
               cancer research between international laboratories and key research
               organizations in cancer research under the umbrella of the ITMO
               Cancer (LIR-G5-LEEM).

               Mesure 21
               Action 21.5 : Identify teams with expertise in new drugs and expand
               information sharing on chemotherapy toxicity after PLA through an
               INCa call for targeted proposals in 2010.
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Accreditation by INCa of early phases
    clinical trials centres (CLIP²)
              Définition of CLIP2

Centres Labellisés INCa
   de Phase Précoce
      in oncology
                                    Objectives of the Network

  Accreditation and support from INCa of early phases centres
                             aims to :
A better access to innovative agents for French patients
o Increase the quality and quantity of early phases clinical trials

o Increase visibility and attractiveness of the French clinical
   research among industrials

o Cover all the various pathologies in Cancer (included:
   Hematology, Pediatric, Rare diseases …)

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                        Evaluation criteria of the centres

    o Project for improvement
    o Quality of operating procedures (QA/QC)
    o Number and type of collaborations with industrials or
    o Publications
    o Activity
    o Organization of the centre (S.O.P …)
    o Dedicated people and structures
    o Technical platforms

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                                              16 accredited centres

                                                                                16 centres

                                                                                    CLCC Villejuif
                       CLCC Caen
                                                                                    CLCC Paris
                                                                                    Saint Louis

                 CHU Nantes                                                          HEGP
                                             CLCC Dijon
                 CLCC Nantes   2

                                   CLCC Clermont                 CLCC Lyon
                                                            2    CHU Lyon sud
               CLCC Bordeaux
               CHU Bordeaux
                                                   CLCC Montpellier
                         CLCC Toulouse
                                                                  CLCC Marseille

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                                 Support from INCa to the CLIP²

     o Annual funding from INCa to the centres

     o Logistic support and audits

     o Regulatory advices /help

                    The funding will be mainly dedicated to:
                Hiring or training people to increase the clinical trials
               quality and the speed of recruitment in early phases
                                     clinical trials

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    o Carry out early phases (Phases I-II) national as well as
      international clinical trials at the best international standard
      of quality.

    o Answer and be involved in the maximum of letters of intent
      (NCI) and projects launched by INCa as well as industrial
      solicitations for early phases clinical trials.

    o Fulfill the increasing regulatory requirements in clinical trials

    o Develop international collaborations

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           INCa – NCI
        Collaboration on
innovative drugs and early phases
          clinical trials
                                                      The collaboration NCI / INCa :
                                                               How it works


                          1                                                                    INCa
                          6                                                                               3
                                                                    5                  French centres Network

•   1:   Firms ask NCI (through CTEP) for a specific development of one of their agents by NCI investigation centres
•   2:   NCI/CTEP issue a « mass solicitation request » to US centres opened now to INCa
•   3:   INCa solicits the French network (16 centres CLIP²) on this specific “letter of intent” (protocol synopsis)
•   4:   Answers from the French centres are reviewed by INCa
•   5:   The French letters of intent are submitted to NCI/CTEP by INCa for formal review
•   6:    If approved by NCI, the project is submitted to the firm for definite approval: Full protocol , drug
         importation to France as well as patients accrual will follow
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                                               Participants to the project

           • NCI/CTEP

           • INCa (French NCI)

           • IRBs and Health authority AFSSAPS (French FDA) :
               eg: Inspections/Audits/ Authorizations of trials/ serious adverse events…

           • The centres: CLIP² network (Institutions/ Investigators)

           • Industrials owner of the molecules (Importation, labeling …)

           • Company of Audits (+QA/QC)

           • Others institutions (LEEM, FNCLCC, CHU, Cengeps, National
           anti cancer donation associations …)

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                           Where are we today ?

           4 solicitations from NCI : inhibitors of different innovative pathways
                                Genentech (Hedgehog inhibitor)
                                      Roche (Notch inhibitor )
                                        Merck (AKT inhibitor)
                                   Osi Pharma ( IGF-1R inhibitor)

                          41 LOI submitted         (by French centres)

                          4 LOI approved by NCI and Firms

               2 full protocols approved by NCI/Firms (2 pending)

           First patient to be enrolled : December 2010 /January 2011
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                                       Planned actions in 2011

o Launch of the four firsts clinical trials

o Set up of the Scientific / Steering committee (January 2011)

o Answer to all mass solicitation requests from NCI/CTEP

o Foster initiatives on unsolicited LOI

o Centres’ audits

o Funding : Private and Academic : LEEM, Cengeps, ARC, big pharma, others…

o National communication on the project

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                             Middle term objectives

o Set up a national network for phases 1 /2 clinical trials

o “Seamless flow” of early phases clinical Trials between NCI and
      the CLIP² through INCa (S.O.P )

o Foster Private companies to participate and use the French
      early phases network

o Increase of unsolicited LOI initiatives

o Extension of collaboration to Phase 3 studies

o Extension to EU

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After Cheese (Camembert), Wine
and Fashion shows, France will be
soon well known for running good
and fast Early phases clinical trials

                                   Merci !

                   52, avenue André Morizet ● 92513 Boulogne-Billancourt Cedex ●
                        Tél. +33 (0) 1 41 10 50 00 ● Fax +33 (0) 1 41 10 50 20
                                   The Network CLIP² is a French
                                    platform dedicated to Early
                                        phases clinical trials
• 16 Centres accredited by a committee of 12 international experts
• All pathologies covered (including Hematology, Pediatric, Rare diseases…)
• Fully Supported and funded by INCa (and other French institutions) :
              • Support and funding of the CLIP² centres
              • Support and funding of the clinical studies (if approved)
• Fast track process for trials authorizations and regulatory requirements :
         • AFSSAPS (French FDA)
         • CPP (French IRBs)
         • and others (DIRC, internal committees , no financial contracts with each centre …)
• Guarantee of quality (highest international standard of QA/QC)
• Scientific/Steering committee including 16 clinical experts
• Quality control and Audits performed by INCa (and inspections by AFSSAPS on
a regular basis).
• Academically driven/International collaborations
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                                              Background Milestones

o Jan 2008 : First Meeting between INCa and NCI/NIH.

o Dec 2008 : 1st solicitation for LOI from CTEP opened to French investigators:
                 a product targeting Hedgehog pathway (Genentech/Roche)

o March / April 2009: 2nd solicitation for LOI : a product targeting Notch pathway
                     (Roche agent) Antagonist of gamma secretase
                         Letter of agreement between NCI and INCa / Meeting NCI-
                         INCa in Paris

o August 2009 : First approval of two LOI by CTEP

o March 2010: Collaboration agreement NCI/INCa signed

o September 2010 : Accreditation of 16 centres (CLIP²)
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                              Main Issues to be solved in the
                                 collaboration NCI/INCa
                                “Room for improvement”
     An amazing work has been done during the last two years,
     however there is still “room for improvement” in :

     • Importation of drugs from US to France

     • Regulatory process : Differences between US and EU

     • One point person NCI    (Ravie Kem?) and   INCa (Beatrice Bussiere)

     • Implication of the industrial is still mandatory

     • OEWG timelines : Start date?/Specific timing for France?

     • Clarify the operating procedures at each step

       At this stage, everybody involved is learning how to walk…
       before running soon….
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                                                    Eligible institutions

          o Healthcare institutions « hospitalo-universitaire »
            (CHU, CLCC)

          o Authorized to treat patients (Surgery and Chemotherapy )

          o Authorized to participate in clinical trials

               (article L1121-13 du Code de la santé publique)

          o One site within one institution

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                                              Cancer plan 2009-2013

       Measure 1: Strengthen resources for multidisciplinary research

     Develop in conjunction with the cancer research clusters a national policiy for
       university hospital-based research integrated sites specialising in cancer
     Continue to organise sites in which only one or two sgnificant conditions are present

     Reaffirm the importance of fundamental research by focusing on the originality of
      research and the importance of interactions between different disciplines

     Accelerate the development and quality of the translational research tools

     Develop an accreditation and networking process for the centres identified for
      implementing the early stages of clinical trials

     Unify the accreditation process by involving academic and industrial partners

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                                       Overview of the different phases of
                                       the project and potential issues (I)
o    Products
       • Choice
        • Pharmaceutical dossier / characterization/ GMP guidelines/product analysis
        • Combination / Other products involved
o    Pharmaceutical companies
       • involvement (headquarters + subsidiaries)
        • Protocol agreement
        • Intellectual property (data, results, findings….)
        • Access to drugs in combination: more than one company involved = many more problems
o    NCI/FDA
      • Assurance/ compensation (US vs EU)
        • Regulatory and Administrative issues / IND requirements ( Annual report, Adverse events, Protocols and
        amendments, pharmaceutical data)
o    Importation/ dispensation of drug
       • Importation authorization / Pharmaceutical dossier/ GMP certification /certificates of analysis/
        • « Shipment »
        • Qualified person
        • Labeling
          • Dispensation
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                                      Overview of the different phases of
                                      the project and potential issues (II)

    o     Protocol/ CRF
           • Dossier for AFSSAPS (Pharmaceutical and clinical) Authorization to start
               • Sponsor (DIRC, Center, Other ?)
               • Procedure, Design, Endpoints (EU and Fr versus US and NCI)
               • Reporting to NCI/CTEP during clinical trial / Audit
               • Scientific and regulatory evaluation
               • Clinical study Audit plan and monitoring of clinical trial (GCP)
    o     Local authorization / Regulatory
           • AFSSAPS / CPP (ethical committee)/ CNIL
               • Insurance
               • Information to the hospital director
               • EU directives

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                              Overview of the different phases of the
                                project and potential issues (III)
o     Investigational centers

         • Identification/Choice (n° of early phases, size, staff, platforms, reputation,
         collaborations, publications ..)

         • Audit/ upgrading centers to NCI standard if needed (GCP and GLP)

         • Registered NCI/FDA (FDA form 1572, investigator supplemental data form (IDF),
         Financial disclosure Form (FDF), CV and other regulatory requirements)
         • Estimation of Patient accrual capacity (evaluation and timing)

         • Collaboration between centers within the network (in case of multicenter study)

         • Biological and Technical platforms
               - Molecular biology /Biostatistics /Genomics /imaging / PK and PD ….
         • Cancéropoles and cooperative groups involvement (FNCLCC , LEEM ….)

         • Steering committee
o     Funding
         • INCa + ?: DRC and APHP ? FNCLCC ? , LEEM ? Firms ?, foundations ? Others …
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                                                Cancer plan 2009-2013

       Measure 1: Strengthen resources for multidisciplinary research
    1.1 Strengthen translational research through dedicated funding based on calls for
        proposals and a policy of multidisciplinary accredited and integrated research sites

    1.2 Support training in translational research for healthcare professionals and researchers
        through the allocation of grants

    1.3 Structure and stimulate research in the early phases of new anti-cancer drug trials

    1.4 Establish research & development partnerships between international laboratories and
        key research in cancer under the umbrella of the ITMO Cancer (LIR-G5-LEEM)

    1.5 Strengthen the interaction between technology transfer offices and economic
        stakeholders to monitor and support projects with the potential for economic

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                                           France is now involved in a
                                              comprehensive action

    o To better prevent cancers         o To develop a better integrated
    o To achieve earlier cancers
      diagnosis                         o To improve equality through
    o To insure high level of quality
      of cancer care                    o To pay constant attention to
    o To promote access to
      innovations and progress          o To foster transversal
                                          information towards population
    o To seek more efficient means        at large, patients, health care
      for cancer prevention,              professionals
      diagnosis and treatment
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 The candidate centres should have :
 o Dedicated people (clinicians, healthcare people ,
       technicians, pharmacists, clinical research specialists…)

 o Dedicated facilities, technical platforms and laboratories

 o Administrative and legal capabilities

 o Highest experience in clinical research (publications …)

 o Capability of working in close collaboration with other

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                                             French Cancer plans

       o 2003: Setting up of the 1st national cancer plan

       o 2004-05: Initiation, organisation through inter-ministerial mission
                  and pre-figuration of INCa

       o 2005-06: Installation of INCa

       o 2007-08: Adaptation of INCa's strategy, follow-up and evaluation
                  of the 1st cancer plan

       o 2009: Setting up of the 2nd National Cancer Plan 2009-2013 by
               the French President, N. Sarkozy.

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