Clinical trial NCT05621837: Quantifying Systemic Immunosuppression to Personalize Cancer Therapy
Official title: Quantifying Systemic Immunosuppression to Personalize Cancer Therapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Melanoma
Breast Cancer
Renal Cell Carcinoma
Urinary Bladder Cancer
Squamous Cell Carcinoma of Head and Neck
Small Cell Carcinoma
NSCLC
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Sponsor class: OTHER
First posted: 2022-11-18
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with five diverse tumor histotypes (n=600) will be collected in parallel clinical case-sets, with power calculation estimated on the basis of MIS validation in melanoma (n=100 patients per histotypes, with the exception of the 200 patients to be enrolled for NSCLC). In addition, a group of age and gender-matched healthy donors (n=400) will be also included to provide normal values of the myeloid-related parameters under physiological 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.

Eligibility criteria: 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

Primary outcomes:
measure: Immunological endpoint
timeFrame: baseline, that is prior to start the therapy (Visit_1)
measure: Immunological endpoint
timeFrame: around one month/before the time-corresponding treatment cycle (Visit_2)
measure: Immunological endpoint
timeFrame: around three months/before the time-corresponding treatment cycle (Visit_3)
measure: Immunological endpoint
timeFrame: Through study completion, an average of 2 year
measure: Clinical endpoint_PFS
timeFrame: Through study completion, an average of 2 year
measure: Clinical endpoint_OS
timeFrame: Through study completion, an average of 2 year
measure: Clinical endpoint_ORR
timeFrame: Through study completion, an average of 2 year
Secondary outcomes:
measure: Myeloid Index Score (MIS)
timeFrame: Through study completion, an average of 2 year
measure: Index score values
timeFrame: Through study completion, an average of 2 year
measure: Transcriptional signatures_PBMC
timeFrame: baseline, that is prior to start the therapy (Visit_1) or at the first disease evaluation (around after three months)
measure: Transcriptional signatures_myeloid cells
timeFrame: baseline, that is prior to start the therapy (Visit_1) or at the first disease evaluation (around after three months)
measure: Phospho-kinome signature result
timeFrame: Through study completion, an average of 2 year
measure: Metabolomic profiles
timeFrame: Through study completion, an average of 2 year
measure: Socio-Economical-Psychological (SEP) score
timeFrame: Through study completion, an average of 2 year
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
Study officials:
affiliation: Fondazione IRCCS Istituto Nazionale Tumori - Milan
name: Licia Rivoltini
role: PRINCIPAL_INVESTIGATOR
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