Quantifying Systemic Immunosuppression to Personalize Cancer Therapy

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano1,000 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

1,000

Conditions

Melanoma Breast Cancer Renal Cell Carcinoma Urinary Bladder Cancer Squamous Cell Carcinoma of Head and Neck

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Immunological endpoint

Frequency, in terms of percentage and absolute count of the defined cell subsets in whole blood and stored PBMC

Time frame: baseline, that is prior to start the therapy (Visit_1)

Immunological endpoint

Frequency, in terms of percentage and absolute count of the defined cell subsets in whole blood and stored PBMC

Time frame: around one month/before the time-corresponding treatment cycle (Visit_2)

Immunological endpoint

Frequency, in terms of percentage and absolute count of the defined cell subsets in whole blood and stored PBMC

Time frame: around three months/before the time-corresponding treatment cycle (Visit_3)

Immunological endpoint

Frequency, in terms of percentage and absolute count of the defined cell subsets in whole blood and stored PBMC

Time frame: Through study completion, an average of 2 year

Clinical endpoint_PFS

Progression-Free Survival (PFS)

Time frame: Through study completion, an average of 2 year

Clinical endpoint_OS

Overall Survival (OS)

Time frame: Through study completion, an average of 2 year

Clinical endpoint_ORR

Overall Response Rate (ORR)

Time frame: Through study completion, an average of 2 year

Secondary Outcomes

Myeloid Index Score (MIS)

Myeloid Index Score (MIS)=0 vs MIS\>0 or higher values

Time frame: Through study completion, an average of 2 year

Index score values

Index score values on plasma cytokine concentration or MDSC-miRs

Time frame: Through study completion, an average of 2 year

Transcriptional signatures_PBMC

Transcriptional signatures identified on PBMC and sorted myeloid cells form whole blood

Time frame: baseline, that is prior to start the therapy (Visit_1) or at the first disease evaluation (around after three months)

Transcriptional signatures_myeloid cells

Transcriptional signatures identified on sorted myeloid cells form whole blood

Time frame: baseline, that is prior to start the therapy (Visit_1) or at the first disease evaluation (around after three months)

Phospho-kinome signature result

Phospho-kinome signature as assessed by Cytof analysis in stored PBMC

Time frame: Through study completion, an average of 2 year

Metabolomic profiles

The concentration of individual metabolites or cluster of metabolites implicated in amino acid and lipid metabolism

Time frame: Through study completion, an average of 2 year

Socio-Economical-Psychological (SEP) score

Socioeconomic and psychological (perceived social isolation) score, calculated through a dedicated questionnaire

Time frame: Through study completion, an average of 2 year

Quantifying Systemic Immunosuppression to Personalize Cancer Therapy

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts