Implementation

motricolor_implementation_gra

Period: 1-48
WPL: AG
Objectives:

  • To develop companion diagnostic tests to molecularly classify CRC tumours using gene expression analysis of FFPE tumour material.
  • To perform full genome gene expression analysis on patients to be enrolled in clinical trials of WP 2, 3 and 4 and classify patients.
  • To transfer gene expression data of all patients to centralized database.

Period: 1-48
WPL: NKI
Objectives:

  • Phase I: To determine the recommended phase 2 dose of CT1 specific medication plus chemotherapy in patients with CT1 subtype CRC.
  • Phase II: To determine the anti-tumour activity, as measured by overall response rate (ORR) of CT1 specific medication in combination with chemotherapy in patients with chemotherapy resistant CT1 subtype CRC.
  • To characterize the safety and tolerability of CT1 specific medication in combination with chemotherapy regimens, as assessed by the incidence and severity of adverse events.
  • To asses anti-tumour activity of CT1 specific medication in combination with chemotherapy, as measured by duration of response, time to response and progression free survival (phase II only).
  • To determine the pharmacokinetic profile of CT1 specific medication in combination with chemotherapy, as measured by plasma concentrations.
  • To explore genetic determinants of response to CT1 specific medication in combination with chemotherapy, as measured by baseline molecular status of potential predictive markers of tumour response.
  • To explore the potential mechanism of resistance to CT1 specific medication in combination with chemotherapy, as measured by gene alterations/expression profiles (e.g. baseline, relapse) in tumour tissue upon progression.

Period: 1-48
WPL: NKI
Objectives:

  • To determine the anti-tumour activity, as measured by overall response rate (ORR) of CT2 specific medication in patients with CT2 subtype CRC.
  • To characterize the safety and tolerability of CT2 specific medication, as assessed by the incidence and severity of adverse events.
  • To assess anti-tumour activity of CT2 specific medication, as measured by progression-free survival (PFS), duration of response, time to response and overall survival (OS).
  • To explore determinants (gene alteration/expression) of response to CT2 specific medication, as measured by baseline molecular status (mutation/amplification/expression) in tumour tissue of potential predictive markers of tumour response.
  • To explore the potential mechanism of resistance to CT2 specific medication, as measured by gene alterations/expression profiles (e.g. baseline, relapse) in tumour tissue upon progression.

Period: 1-48
WPL: VHIO
Objectives:

  • To determine the anti-tumour activity, as measured by overall response rate (ORR) of CT3 specific medication in patients with chemotherapy resistant CT2 subtype CRC.
  • To assess anti-tumour activity of CT3 specific medication as measured by duration of response, time to response and progression free survival (PFS) and overall survival (OS).
  • To characterize the safety and tolerability of CT3 specific medication as assessed by the incidence and severity of adverse events.
  • To explore the potential mechanisms of response to CT3 specific medication, as measured by baseline molecular status of potential predictive markers of tumour response.
  • To explore the potential mechanism of resistance to CT3 specific medication, as measured by gene alterations/expression profiles (e.g. baseline, relapse) in tumour tissue upon progression.
  • To identify a potential profile of somatic mutations (tumour mutanome) by analysing a tumour sample and normal cells (PBMCs) by next generation sequencing techniques (exome RNA-seq).
  • To monitor circulating tumour DNA and correlate with response and resistance.

Period: 24-48
WPL: ICO
Objectives:

  • To obtain the bioinformatics molecular characterization of tumours from patients included in the three trials through the bioinformatics analysis of somatic mutations (DNA-seq).
  • To identify potential mechanisms involved in the response and or resistance of tumours.
  • To identify mutated proteins candidate to act as epitopes to the immune system and trigger an immune response for patients included in clinical trial 3.
  • To assist with statistical design, interim analysis and full analysis of the clinical trials.

Period: 6-40
WPL: ICO
Objectives:

  • To determine if a T cell response in peripheral blood against tumour neoepitopes can be detected in MSC-like CRC patients.
  • Determine if the clinical response to CT3 antobody can be predicted before treatment by a T cell response in peripheral blood against tumour neoepitopes.
  • Determine if the clinical response to CT3 antobody can be predicted early after treatment by a T cell response in peripheral blood against tumour neoepitopes.

Period: 1-48
WPL: UNITO
Objectives:

  • To identify patient-specific genetic biomarker to be detected in the blood.
  • To molecular monitor response to therapy in the blood.
  • To identify mechanisms of secondary resistance and the emergence of resistant clones.

Period: 1-48
WPL: VHIO
Objectives:

  • To provide the overall scientific direction and to drive the progress of the project, steering efforts of the partners for the achievement of the project’s objectives and milestones and ensuring that the work is undertaken with appropriate quality levels.
  • To set-up a project management structure that ensures an efficient operational management including administrative, financial and legal issues, and appropriate liaison with the European Commission.
  • To ensure that the project is appropriately managed according to the work plan, supporting the Coordinator in organising and supervising the work.
  • To provide resources, procedures and tools for ensuring that all results are delivered on time, with an adequate quality level and within cost, including quality control procedures on deliverables and interim and final review of the project achievements from a management perspective.
  • To enable the appropriate communication and work dynamics to help drive the whole Consortium as a team towards successful completion.

Period: 1-48
WPL: VHIO
Objectives:

  • To design a plan that allows for optimal communication within the project and the dissemination of information and knowledge generated by the project to relevant stakeholders and the general community.
  • To create awareness and understanding of the progress that takes place in the context of MoTriColor among stakeholders.
  • To undertake extensive dissemination activities according to the communication plan.
  • To design and produce the communication tools that will be needed to implement the plan.
  • To devise sustainability models for MoTriColor, which ensure the implementation of the results developed during the project.