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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)

s.bielack@klinikum-stuttgart.de

….

• 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)

s.bielack@klinikum-stuttgart.de

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