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

Mestastatic ColoRectal Cancer Clinical Trial

Official title:

A Proof-of-concept Study Investigating the Comparison of the RAS Mutational Status Between Primary Tumor and Metastasis in Patients Affected by Metastatic Colorectal Cancer on the Basis of Different Chemotherapeutic Regimens

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04338542
• Other study ID #: IOSI-ICP-001
• Status: Completed
• Start date: April 8, 2020
• Est. completion date: July 2, 2020

Study information

• Verified date: August 2020
• Source: Ente Ospedaliero Cantonale, Bellinzona
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: July 2, 2020
• Est. primary completion date: July 2, 2020
• Gender: All
• Age group: 18 Years and older

Eligibility

General inclusion criteria (valid for all the three cohorts):

• 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;

General exclusion criteria (valid for all the three cohorts):

• inadequate material for the molecular characterization of the primary tumour and/or of the related metastasis;

• insufficient amount (%) of tumour cells;

Specific inclusion criteria for each group:

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Mestastatic ColoRectal Cancer

Intervention

Genetic:
• Tumor biobsies analysis
Analysis on archived tumor biopsies

Locations

Country	Name	City	State
Switzerland	Istituto Oncologico della Svizzera Italiana	Bellinzona

Sponsors (3)

Lead Sponsor	Collaborator
Sara De Dosso	Clinical Trial Unit Ente Ospedaliero Cantonale, Istituto Cantonale di Patologia

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of RAS mutant clones in the metastatic lesion	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	6 months
Secondary	Molecular patterns other than RAS	Compare molecular patterns other than RAS in the primary tumor and paired liver metastasis	6 months