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Molecularly guided trials with specific treatment strategies in patients with advanced newly molecular defined subtypes of colorectal cancer (MoTriColor)

Objective

Colorectal cancer (CRC) is increasingly being recognized as a heterogeneous disease with distinct molecular subtypes. These subtypes have different biological processes at the basis of their disease and consequently their prognosis and responses to therapy are also different.
We have previously developed molecular diagnostic assays using a single platform on routine FFPE tumour biopsies. These assays identify gene expression profiles with distinct prognosis and drug response phenotypes (CMS4/c-type, BRAF mutant-like, and MSI-like). Our overall objective is to develop targeted therapies more effective than the current therapies that do not take advantage of molecular classification of the disease to select patients for therapy. We therefore propose to perform 3 two-stage single arm multi-centre open-label phase II studies based on solid preclinical evidence and a sound scientific rationale for these subgroups of CRC patients: 1) combination of chemotherapy and a TGF-βR inhibitor (LY2157299) in patients presenting a C-type signature; 2) vinorelbine in patients with a BRAFm-like signature; and 3) an immunotherapeutic anti-PD-L1 drug (MPDL3280A) in combination with bevacizumab in patients with a MSI-like signature. The primary objectives of these studies are to determine the clinical efficacy (progression-free survival as primary endpoint), safety and tolerability of the experimental treatments in these molecularly selected populations. Mutation analysis at the beginning of treatment and monitoring by liquid biopsies might reveal further biomarkers that predict response in retrospective analysis.
The project outcomes may have a significant impact in CRC patients with poor-risk prognosis worldwide as 40-50% of them present gene expression profiles matching one of the 3 approaches. Around 40,000 European CRC patients may potentially benefit from the results. Also, these may be translated to other cancer types with equivalent gene expression patterns/deregulated signalling pathways.

Call for proposal

H2020-PHC-2014-2015

See other projects for this call

Sub call

H2020-PHC-2014-two-stage

Coordinator

FUNDACIO PRIVADA INSTITUT D'INVESTIGACIO ONCOLOGICA DE VALL-HEBRON (VHIO)
Net EU contribution
€ 1 049 062,50
Address
Calle Nazaret 115-117
08035 Barcelona
Spain
Activity type
Research Organisations
Non-EU contribution
€ 0,00

Participants (9)

INSTITUT CATALA D'ONCOLOGIA
Spain
Net EU contribution
€ 683 427,50
Address
Av Gran Via De L'hospitalet 199-203
08908 L'hospitalet Del Llobregat
Activity type
Research Organisations
Non-EU contribution
€ 0,00
Agendia BV
Netherlands
Net EU contribution
€ 905 250,00
SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Address
Science Park 406
1098XH Amsterdam
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Netherlands
Net EU contribution
€ 643 218,75
Address
Plesmanlaan 121
1066 CX Amsterdam
Activity type
Research Organisations
Non-EU contribution
€ 0,00
EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER AISBL
Belgium
Net EU contribution
€ 331 000,00
Address
Avenue E. Mounier 83
1200 Brussels
Activity type
Research Organisations
Non-EU contribution
€ 0,00
Region
Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest
L'AZIENDA SOCIO SANITARIA TERRITORIALE (ASST) GRANDE OSPEDALE METROPOLITANO NIGUARDA
Italy
Net EU contribution
€ 207 501,25
Address
Piazza Ospedale Maggiore 3
20162 Milano
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Non-EU contribution
€ 0,00
Region
Nord-Ovest Lombardia Milano
 
FUNDACION PARA LA INVESTIGACION DEL HOSPITAL CLINICO DE LA COMUNITAT VALENCIANA, FUNDACION INCLIVA
Spain
Net EU contribution
€ 143 031,50
Address
Av Menendez Pelayo 4
46010 Valencia
Activity type
Research Organisations
Non-EU contribution
€ 0,00
Region
Valencia/València Comunitat Valenciana
 
UNIVERSITA DEGLI STUDI DELLA CAMPANIA LUIGI VANVITELLI
Italy
Net EU contribution
€ 146 500,50
Address
Viale Abramo Lincoln 5
81100 Caserta
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
UNIVERSITA DEGLI STUDI DI TORINO
Italy
Net EU contribution
€ 682 125,00
Address
Via Giuseppe Verdi 8
10124 Torino
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
KATHOLIEKE UNIVERSITEIT LEUVEN
Belgium
Net EU contribution
€ 157 625,50
Address
Oude Markt 13
3000 Leuven
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
Region
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven