Clinical trial NCT04338542: A Retrospective Study Project of Clinico-molecular Characterization in Patients With Metastatic Colorectal Cancer
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Mestastatic ColoRectal Cancer
Lead sponsor: Ente Ospedaliero Cantonale, Bellinzona
Sponsor class: OTHER
Collaborators: name: Istituto Cantonale di Patologia
name: Clinical Trial Unit Ente Ospedaliero Cantonale
First posted: 2020-04-08
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: metastatic ColoRectal Cancer patients exhibiting RAS mutation and who received a treatment

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change of RAS mutant clones in the metastatic lesion
timeFrame: 6 months
Secondary outcomes:
measure: Molecular patterns other than RAS
timeFrame: 6 months
Other outcomes:
Locations:
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana
Study officials:
affiliation: Ente Ospedaliero Cantonale, Bellinzona
name: Sara De Dosso, MD
role: STUDY_CHAIR
affiliation: Istituto Cantonale Patologia
name: Milo Frattini, MD
role: PRINCIPAL_INVESTIGATOR
References: