Breast Cancer, Melanoma, NSCLC, Renal Cell Carcinoma, Small Cell Carcinoma, Squamous Cell Carcinoma of Head and Neck, Urinary Bladder Cancer
Conditions
Brief summary
The Serpentine (Stratify cancER PatiENTs by ImmuNosupprEssion) project, represents the most consistent effort so far attempted to translate MDSC into clinical practise by producing an off-the-shelf compliant assay for quantifying these cells in peripheral blood.
Detailed description
The study will demonstrate that this assay helps personalizing cancer therapies by tailoring them to immune patient features. The project will also take advantage of innovative and high-throughput techniques to define additional MDSC related biomarkers and, most importantly, to identify novel drugs for Myeloid-derived Suppressor Cells (MDSC) blocking in predisposed patients. Finally,it will perform the first survey assessing the link between MDSC and perceived social isolation, an emerging western social problem recently shown to cause myeloid cell dysfunction and immunosuppression though neuroendocrine circuits. Globally, the Serpentine proposal has the ambitious goal to translate into the clinical oncological practise the use of MDSC quantification as a tool for the systematic assessment of systemic immunosuppression, providing at the same time operational insights into the strategies to overcome this pillar mechanism of cancer progression.
Interventions
OTHERMDSC quantification
Blood sample will be collected at baseline and during therapy, and, optionally, in case of disease progression (PD).
Sponsors
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
* Histologically documented diagnosis of metastatic/locally advanced melanoma, hormone-refractory breast cancer, RCC and UC, SCCHN, SCC or NSCLC, stage III resectable NSCLC will also be included * Will and ability to comply with the protocol * Willingness and ability to provide an adequate archival Formalin-Fixed Paraffin-Embedded (FFPE) tumor sample available for exploratory biomarker analysis * Age from 18 to 90 years at the time of recruitment * ECOG Performance Status \<= 2 * Understanding and signature of the informed consent * Consenting to participate to the socio-economical-psychological survey
Exclusion criteria
* Known history of HIV infection * Serious neurological or psychiatric disorders * Pregnancy or lactation * Inability or unwillingness of participant to give written informed consent * Inability or unwillingness to be regularly followed up at the same center
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunological endpoint | baseline, that is prior to start the therapy (Visit_1) | Frequency, in terms of percentage and absolute count of the defined cell subsets in whole blood and stored PBMC |
| Clinical endpoint_PFS | Through study completion, an average of 2 year | Progression-Free Survival (PFS) |
| Clinical endpoint_OS | Through study completion, an average of 2 year | Overall Survival (OS) |
| Clinical endpoint_ORR | Through study completion, an average of 2 year | Overall Response Rate (ORR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transcriptional signatures_myeloid cells | baseline, that is prior to start the therapy (Visit_1) or at the first disease evaluation (around after three months) | Transcriptional signatures identified on sorted myeloid cells form whole blood |
| Metabolomic profiles | Through study completion, an average of 2 year | The concentration of individual metabolites or cluster of metabolites implicated in amino acid and lipid metabolism |
| Socio-Economical-Psychological (SEP) score | Through study completion, an average of 2 year | Socioeconomic and psychological (perceived social isolation) score, calculated through a dedicated questionnaire |
| Phospho-kinome signature result | Through study completion, an average of 2 year | Phospho-kinome signature as assessed by Cytof analysis in stored PBMC |
| Myeloid Index Score (MIS) | Through study completion, an average of 2 year | Myeloid Index Score (MIS)=0 vs MIS\>0 or higher values |
| Index score values | Through study completion, an average of 2 year | Index score values on plasma cytokine concentration or MDSC-miRs |
| Transcriptional signatures_PBMC | baseline, that is prior to start the therapy (Visit_1) or at the first disease evaluation (around after three months) | Transcriptional signatures identified on PBMC and sorted myeloid cells form whole blood |
Countries
Italy
Contacts
Primary ContactLicia Rivoltini
Backup ContactPaola Frati
Outcome results
None listed