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

Completed

• Conditions: Mestastatic ColoRectal Cancer
• Interventions: Genetic: Tumor biobsies analysis

• Registration Number: NCT04338542
• Lead Sponsor: Sara De Dosso

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.

Study Timeline

• Study First Submitted: 2020-04-05
• Study First Submitted QC: 2020-04-05
• Study Start: 2020-04-08
• Study First Posted: 2020-04-08
• Primary Completion: 2020-07-02
• Study Completion: 2020-07-02
• Status Verified: 2020-08
• Last Update Submitted: 2020-08-07
• Last Update Posted: 2020-08-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
neoadjuvant chemotherapy plus bevacizumab	Tumor biobsies analysis	Patients treated with surgery of the primary tumor, neoadjuvant chemotherapy plus bevacizumab and, finally, the surgical resection of liver metastasis.
neoadjuvant chemotherapy	Tumor biobsies analysis	Patients treated with surgery of the primary tumor, neoadjuvant chemotherapy and, finally, the surgical resection of liver metastasis.
control group	Tumor biobsies analysis	Patients presenting with synchronous primary tumour and metastasis resected without any preoperative systemic therapy.

Primary Outcome Measures

Name	Time	Method
Change of RAS mutant clones in the metastatic lesion	6 months	To confirm that the administration of an antiangiogenic treatment in mCRC RAS mutant patients before liver metastasis resection leads to a significant reduction of RAS mutant clones in the metastatic lesion

Secondary Outcome Measures

Name	Time	Method
Molecular patterns other than RAS	6 months	Compare molecular patterns other than RAS in the primary tumor and paired liver metastasis

Trial Locations

Locations (1)

Istituto Oncologico della Svizzera Italiana; 🇨🇭 Bellinzona, Switzerland