Embed Size (px)
Citation preview
Access to Clinical Trials
International InitiativesStefan Bielack
Cooperative Osteosarcoma Study Group COSS
Stuttgart Cancer Center
Klinikum Stuttgart – Olgahospital
Zentrum für Kinder-, Jugend- und Frauenmedizin
Pädiatrie 5 (Onkologie, Hämatologie, Immunologie)
….
• diagnostic delays => tumor load
AYA: (Some) reasons
for prognostic disadvantages
• diagnostic delays => tumor load
• distinct tumor biology
• distinct pharmacology
AYA: (Some) reasons
for prognostic disadvantages
AYA need not experience more toxicity than
children!
• RMS (COG, n=657)
AYA => less marrow & mucosal tox., more neuropathy(Gupta et al., Cancer. 2012)
• Ewing (EURO-E.W.I.N.G. 99, n=851)
AYA => less marrw & mucosal tox, vomiting(Juergens et al., Pediatr Blood Cancer 2006)
• Osteo (Livestrong metaanalysis, n=4,838)
AYA => less thrombopenia, neutropenia, DOC(Collins et al., J Clin Oncol 2013)
• diagnostic delays => tumor load
• distinct tumor biology
• distinct pharmacology
• compliance
• treatment infrastructures
AYA: (Some) reasons
for prognostic disadvantages
Pediatric n DFS Adult n DFS
FRALLE 83 84 48% (6 years) LALA 85 31 32% (4 years)
FRALLE 93 77 72% (5 years) LALA 94 100 49% (5 years)
CCG 1800 196 64% (6 years) CALGB 103 38% (6 years)
AIEOP 150 80% (OS, 2 years) GIMEMA 95 71% (OS, 2 years)
DCOG 6–9 47 71% (5 years) HOVON 44 37% (5 years)
• diagnostic delays => tumor load
• distinct tumor biology
• distinct pharmacology
• compliance
• treatment infrastructures
• lack of trial participation
AYA: (Some) reasons
for prognostic disadvantages
Bleyer WA. The adolescent gap in cancertreatment.J Registry Manage 1996; 23: 114-5
AYA: Trial participation
Age and survival improvementsBleyer, Med Pediatr Oncol 2002
….
….
….
Distinct AYA outcomes
Lack of trial participation – why?
• (Non-) Availability
• Lack of recruitment if available
AYA
Lack of available trials / „industry sponsored“
• Orphan diseases with limited industry interest
• Traditional „adult“ trials only start at age 18
• „Pediatric“ phase I/II trials often
- start late (after adult license)
- based upon disease instead mode of action
- stop at age 18 („PIP“)
- don‘t recruit very well
AYA trials
Recent initiatives to bridge the „18“ age gap“
AYA trials
Recent initiatives to bridge the „18“ age gap“
AYA trials
Recent initiatives to bridge the „18“ age gap“
Distinct AYA outcomes
Lack of trial participation – why?
• (Non-) Availability
• Lack of recruitment if available
AYA – Lack of trial recruitment
Example: Osteosarcoma – an AYA cancer
European and American Osteosarcoma StudyCOG Childrens’ Oncology Group
COSSCooperative Osteosarcoma Study Group
EOIEuropean Osteosarcoma Intergroup
SSGScandinavian Sarcoma Group
COG Childrens’ Oncology Group
COSSCooperative Osteosarcoma Study Group
EOIEuropean Osteosarcoma Intergroup
SSGScandinavian Sarcoma Group
European and American Osteosarcoma Study
eligible:
≤40 yearsat osteosarcoma diagnosis
EURAMOS Recruitment 04/05 – 06/11
Thanks to EURAMOS-CDC,
MRC London
2.260 patients
from 326 institutions
in 17 countries Group | Freq. Percent Cum.
------------+-----------------------------------
COG | 1,164 51.50 51.50
COSS | 520 23.01 74.51
EOI | 457 20.22 94.73
SSG | 119 5.27 100.00
------------+-----------------------------------
Total | 2,260 100.00
AYA – Lack of trial recruitment
Example: Osteosarcoma – an AYA cancer
European and American Osteosarcoma Study EURAMOS
Age-specific recruitment
0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39
0
0,2
0,4
0,6
0,8
1
1,2
1,4
SEER
EURAMOS
Medical Oncologymissing (ca. 600 pts)
EURAMOS: Age-specific recruitment different
80% Ped
20% Med
France:
Different trial, same lack of „adult“ participation
Would it be feasibleto perform such
trials only in selectedlarge centers?
EURAMOS Patients per center
Pts/year centers pts
<1 185 (56.4%) 487 (22.5%)
1-1.99 90 (27.4%) 688 (31.7%)
2-2.99 34 (10.4%) 485 (22.3%)
3-3.99 14 (4.3%) 280 (12.9%)
4-4.99 2 (0.6%) 53 (2.4%)
>5 3 175
Is it easy to run a trial-in many centers?-in your own center?
ICH Topic E6Guideline for Good Clinical Practice
Documentation to be held by investigator/institution
for clinical trials• Investigators brochure (+ updates) or SmPC
• Protocol and amendments (signed)
• Information sheet and consent form (+ updates)
• Financial aspects
• Insurance statements
• Signed agreements between parties
• EC opinion and composition
• MRHA authorisation
• Investigators CVs
• Medical and laboratory tests, including normal ranges
• Medicine labels
• Instructions for medicine use
• Shipping records
• Certificates of analysis
• Decoding procedures
• Master randomisation list
• Monitoring reports (pre-trial, initiation, close-out etc)
• List of persons responsibilities delegated to (+ updates)
• CRFs and corrections
• SAE notifications from investigators and to EC and MRHA
• EC/MRHA annual reports and final reports
• Subject screening log
• Subject identification code list
• Subject enrolment log
• IMP accountability at site
• Record of retained tissues
• Documentation of IMP destruction
• Completed subject identification code list
• Audit certificate
• Clinical study report
• Perform trials across the age ranges
• Take the effort and open (investigator-initiated)
trials at your center!
• Enrol your (AYA) patients!
How to proceed for better AYA care?
Access to Clinical Trials
International Initiatives
Stefan Bielack
Cooperative Osteosarcoma Study Group COSS
Stuttgart Cancer Center
Klinikum Stuttgart – Olgahospital
Zentrum für Kinder-, Jugend- und Frauenmedizin
Pädiatrie 5 (Onkologie, Hämatologie, Immunologie)
European Societies
Controversy session:
Adolescent oncology: pediatric or adult territory?Istanbul, 1 October 2006 , 13:45-14:45
Presentation 1: Pediatric view speaker Stefan Bielack, DE
Presentation 2: Adult view speakerIan Judson, UK
Presentation 3: Advocate for multidisciplinary team of both pediatric and adult oncologistsGunnar Saeter, NO
EXECUTIVE SUMMARY OF SIOPE
EUROPEAN CANCER PLAN
FOR CHILDREN AND ADOLESCENTS
------
Cancer in young people is rare, but it is still a major health issue in Europe. Each year, more
than 6,000 young people in Europe die of cancer. There are more than 300,000 European childhood
cancer survivors (in 2020, they will be nearly half a million): two-thirds of them have some late side
effects of treatment, that are severe and impact on the daily life of half of those affected.
Within the European Network for Cancer research in Children and Adolescents (ENCCA), SIOPE and
the European paediatric haematology-oncology community have established a long-term sustainable
Strategic Plan to increase the cure rate and the quality of survivorship for children and young
people with cancer over the next ten years. The ultimate goal is to increase the disease- and late-
effect- free survival after 10 years from the diagnosis, and beyond.
Seven medical and scientific objectives have been set up to achieve these goals:
• Innovative treatments: ....
• Precision cancer medicine: ....
• Tumour biology: ....
• Equal access: ....
•TYA: to address the specific needs of
teenagers and young adults (TYA),
in cooperation with adult oncology• Quality of survivorship: ....
• Causes of cancer....
SIOPE will steer and coordinate the effective implementation of this Strategic Plan, together with
the European Clinical Trial Groups (ECTGs) and the National Paediatric Haematology Oncology
Societies (NAPHOS), in close cooperation with the parents, patients, and survivors’ advocates from
the European Regional Committee of Childhood Cancer International (CCI). ....
Cancer in Adolescents and Young Adults (AYA)
Working Group
Mission of the Joint ESMO-SIOPE Working Group on
Cancer in Adolescents and Young Adults (AYA)
The goal of the joint Working Group s to promote education in
cancer topics specific to this population. It is a joint venture
between the European Society for Medical Oncology (ESMO) and
the European Society for Pediatric Oncology (SIOPE) created in
2016, following collaborative efforts in the educational arena
between the two societies since 2014.
ESMO-SIOPE AYA Activities and Responsibilities (1)
• Increase awareness amongst the medical and pediatric oncology
communities & enhance knowledge on specific AYA cancer issues
• Serve as a primary resource for new CME opportunities through
production of specific educational and scientific programs.
• Liaison with other ESMO committees when specific actions are
needed, e.g. providing advice at policy level to optimize
approaches to prevention, diagnosis, treatment and long term
follow-up of these specific patient populations.
Selected AYA Working Group Accomplishments
• Regular teleconferences & face-to-face meetings (Yes!!! Medical
and pediatric oncologists talk to each other!)
• Dedicated space on the ESMO website
http://www.esmo.org/About-Us/Who-We-Are/Educational-
Committee/Adolescents-and-Young-Adults-Working-Group
• e-learning modules on
• Cancer in adolescents and young adults
• Breast cancer in young women
• Colorectal cancer in young adults: The focus on hereditary
cancer syndromes
• Development of further modules in progress
• Joint ESMO-SIOPE AYA symposia at ESMO conferences
• Agreement on producing a joint handbook on AYA cancer
• ESMO-SIOPE Survey on AYA Care
Cancer in Adolescents and Young Adults (AYA)
Working Group
European Network
European Network
National activitiesby medical and pediatric oncologists
…. and many more
…
Thank you!
Stefan Bielack
12.05.2018
