CORDIS
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CORDIS

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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.
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Coordinator

FUNDACIO PRIVADA INSTITUT D'INVESTIGACIO ONCOLOGICA DE VALL-HEBRON

Address

Calle Nazaret 115-117
08035 Barcelona

Spain

Activity type

Research Organisations

EU Contribution

€ 1 147 455

Participants (10)

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INSTITUT CATALA D'ONCOLOGIA

Spain

EU Contribution

€ 829 320

Agendia NV

Netherlands

EU Contribution

€ 905 250

STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS

Netherlands

EU Contribution

€ 771 611

EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER AISBL

Belgium

EU Contribution

€ 580 500

L'AZIENDA SOCIO SANITARIA TERRITORIALE (ASST) GRANDE OSPEDALE METROPOLITANO NIGUARDA

Italy

EU Contribution

€ 265 896

AZIENDA OSPEDALIERA OSPEDALE NIGUARDA CA' GRANDA

Italy

FUNDACION PARA LA INVESTIGACION DEL HOSPITAL CLINICO DE LA COMUNITAT VALENCIANA, FUNDACION INCLIVA

Spain

EU Contribution

€ 271 424

UNIVERSITA DEGLI STUDI DELLA CAMPANIA LUIGI VANVITELLI

Italy

EU Contribution

€ 266 143

UNIVERSITA DEGLI STUDI DI TORINO

Italy

EU Contribution

€ 682 125

KATHOLIEKE UNIVERSITEIT LEUVEN

Belgium

EU Contribution

€ 277 268

Project information

Grant agreement ID: 635342

Status

Closed project

  • Start date

    1 October 2015

  • End date

    30 September 2019

Funded under:

H2020-EU.3.1.3.

  • Overall budget:

    € 5 996 992

  • EU contribution

    € 5 996 992

Coordinated by:

FUNDACIO PRIVADA INSTITUT D'INVESTIGACIO ONCOLOGICA DE VALL-HEBRON

Spain