A Retrospective Study Project of Clinico-molecular Characterization in Patients With Metastatic Colorectal Cancer

NCT ID: NCT04338542

Last Updated: 2020-08-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 45 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-04-08
• Study Completion Date: 2020-07-02

Brief Summary

This is a retrospective, translational, proof-of-concept study on tumor biopsies done on patients affected by mCRC and exhibiting RAS mutation.

For each patient it will be selected the tissue biopsies of primary tumour and of paired resected metastasis.

Detailed Description

the study implies the subdivision into three groups with a 1:1:1 ratio.

• The first group includes patients treated with surgery of the primary tumor, neoadjuvant chemotherapy plus bevacizumab and, finally, the surgical resection of liver metastasis.
• The second group is similar to group one, with the exception that patients were not treated with a bevacizumab-based regimen.
• The third group, the control group, includes patients presenting with synchronous primary tumour and metastasis resected without any preoperative systemic therapy

Genomic DNA from formalin-fixed paraffin-embedded (FFPE) tissues from the primary tumor and metastatic lesions will be extracted. The genomic DNA will be assessed for the RAS mutational status in a quantitative and qualitative manner using two different approaches: a real-time PCR approach using the SensiScreen® kit (PentaBase Aps) and a next-generation sequencing approach using the Ion Torrent platform by applying the Ion AmpliSeq™ Cancer Hotspot Panel v2 (ThermoFisher Scientific). The real-time PCR is able to provide the relative quantification of the RAS mutant allele by comparing the Ct value of the mutation with respect to the Ct of the reference gene. This ratio will be calculated for both the primary tumor and for the metastasis and then compared. Ion Torrent gives directly the percentage of the mutant allele in each sample. Furthermore, the Cancer Hotspot Panel v2 provides data (both quantitative and qualitative) about the mutational status of additional 49 genes, including the most relevant and frequently mutated genes in CRC (i.e.: APC, TP53, PIK3CA, BRAF and PTEN) and the relative mutational pattern of the primary tumor and the one of the distant metastasis will be compared.

Conditions

Mestastatic ColoRectal Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

neoadjuvant chemotherapy plus bevacizumab

Patients treated with surgery of the primary tumor, neoadjuvant chemotherapy plus bevacizumab and, finally, the surgical resection of liver metastasis.

Tumor biobsies analysis

Intervention Type: GENETIC

Analysis on archived tumor biopsies

neoadjuvant chemotherapy

Patients treated with surgery of the primary tumor, neoadjuvant chemotherapy and, finally, the surgical resection of liver metastasis.

Tumor biobsies analysis

Intervention Type: GENETIC

Analysis on archived tumor biopsies

control group

Patients presenting with synchronous primary tumour and metastasis resected without any preoperative systemic therapy.

Tumor biobsies analysis

Intervention Type: GENETIC

Analysis on archived tumor biopsies

Interventions

Tumor biobsies analysis

Analysis on archived tumor biopsies

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• patients with biopsy-proven, stage IV CRC;
• RAS mutation at diagnosis;
• availability of tissue biopsy/resection of both primary tumour and paired liver metastasis for the molecular characterization;

1. st group:

• first-line bevacizumab plus chemotherapy before resection of liver metastases;
• metastases must be resected metachronously with respect to the primary tumor.

2. nd group:

• first-line chemotherapy without bevacizumab before resection of liver metastases;
• metastases must be resected metachronously with respect to the primary tumor.

3. rd group:

• no systemic therapy (immediate surgical resection of primary tumor and paired liver metastases);
• primary tumour and metastasis can be synchronous or metachronous.

Exclusion Criteria

• inadequate material for the molecular characterization of the primary tumour and/or of the related metastasis;
• insufficient amount (%) of tumour cells;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istituto Cantonale di Patologia

OTHER

Sponsor Role: collaborator

Clinical Trial Unit Ente Ospedaliero Cantonale

OTHER

Sponsor Role: collaborator

Sara De Dosso

OTHER

Sponsor Role: lead

Responsible Party

Sara De Dosso

Department Senior

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sara De Dosso, MD

Role: STUDY_CHAIR

Ente Ospedaliero Cantonale, Bellinzona

Milo Frattini, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Cantonale Patologia

Locations

Istituto Oncologico della Svizzera Italiana

Bellinzona, , Switzerland

Countries

Switzerland

Other Identifiers

IOSI-ICP-001

Identifier Type: -

Identifier Source: org_study_id