Quantifying Systemic Immunosuppression to Personalize Cancer Therapy (Serpentine)

April 29, 2025 updated by: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 86 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Metastatic melanoma patients
MDSC quantification in Metastatic melanoma patients undergoing first/second-line treatment with BRAF and MEK inhibitors (BRAFi+MEKi) or immune checkpoint inhibitors (antagonists of PD-1 or CTL4, or both) (n=100);
Other: MDSC quantification
Blood sample will be collected at baseline and during therapy, and, optionally, in case of disease progression (PD).
hormone receptor positive/Human Epidermal growth factor Receptor-2 negative cancer patients
MDSC quantification in Metastatic HR+(hormone receptor positive)/ HER2-(Human Epidermal growth factor Receptor-2 negative) breast cancer patients already treated with a combination of an hormonal agent and a CDK(Cyclin-dependent kinase)4/6 inhibitor and receiving chemotherapy (n=100);
Other: MDSC quantification
Blood sample will be collected at baseline and during therapy, and, optionally, in case of disease progression (PD).
Advanced RCC(renal cell carcinoma) patients
MDSC quantification Advanced RCC patients receiving immune checkpoint inhibitors (antagonists of PD-1, PD-L1 or CTL4, or combinations) or anti-angiogenics alone or combined with immune checkpoint inhibitors; locally advanced/metastatic UC(Urothelial Carcinoma) patients receiving first-line chemotherapy, immune checkpoint inhibitors or combinations (n=100);
Other: MDSC quantification
Blood sample will be collected at baseline and during therapy, and, optionally, in case of disease progression (PD).
SCCHN or SCC(Small Cell Carcinoma) patients
MDSC quantification in SCCHN or SCC(Small Cell Carcinoma) patients treated with first-line chemotherapy, cetuximab,immune checkpoint inhibitors or combinations (n=100).
Other: MDSC quantification
Blood sample will be collected at baseline and during therapy, and, optionally, in case of disease progression (PD).
NSCLC patients
MDSC quantification in NSCLC patients undergoing radical surgery for stage III cancer (n=100);patients with unresectable/metastatic NSCLC receiving first line treatment with chemotherapy, immune checkpoint inhibitors (antagonists of PD-1, PD-L1 or CTL4) or combinations (n=100).
Other: MDSC quantification
Blood sample will be collected at baseline and during therapy, and, optionally, in case of disease progression (PD).
Age and gender-matched healthy donors
Age and gender-matched healthy donors (n=400) will be enrolled in the study, to allow us investigating the same immunological parameters under physiological conditions and define normal values for the myeloid-related biomarkers here assessed.
Other: MDSC quantification
Blood sample will be collected at baseline and during therapy, and, optionally, in case of disease progression (PD).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Immunological endpoint
Time Frame: 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
baseline, that is prior to start the therapy (Visit_1)
Immunological endpoint
Time Frame: around one month/before the time-corresponding treatment cycle (Visit_2)
Frequency, in terms of percentage and absolute count of the defined cell subsets in whole blood and stored PBMC
around one month/before the time-corresponding treatment cycle (Visit_2)
Immunological endpoint
Time Frame: around three months/before the time-corresponding treatment cycle (Visit_3)
Frequency, in terms of percentage and absolute count of the defined cell subsets in whole blood and stored PBMC
around three months/before the time-corresponding treatment cycle (Visit_3)
Immunological endpoint
Time Frame: Through study completion, an average of 2 year
Frequency, in terms of percentage and absolute count of the defined cell subsets in whole blood and stored PBMC
Through study completion, an average of 2 year
Clinical endpoint_PFS
Time Frame: Through study completion, an average of 2 year
Progression-Free Survival (PFS)
Through study completion, an average of 2 year
Clinical endpoint_OS
Time Frame: Through study completion, an average of 2 year
Overall Survival (OS)
Through study completion, an average of 2 year
Clinical endpoint_ORR
Time Frame: Through study completion, an average of 2 year
Overall Response Rate (ORR)
Through study completion, an average of 2 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Myeloid Index Score (MIS)
Time Frame: Through study completion, an average of 2 year
Myeloid Index Score (MIS)=0 vs MIS>0 or higher values
Through study completion, an average of 2 year
Index score values
Time Frame: Through study completion, an average of 2 year
Index score values on plasma cytokine concentration or MDSC-miRs
Through study completion, an average of 2 year
Transcriptional signatures_PBMC
Time Frame: 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
baseline, that is prior to start the therapy (Visit_1) or at the first disease evaluation (around after three months)
Transcriptional signatures_myeloid cells
Time Frame: 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
baseline, that is prior to start the therapy (Visit_1) or at the first disease evaluation (around after three months)
Phospho-kinome signature result
Time Frame: Through study completion, an average of 2 year
Phospho-kinome signature as assessed by Cytof analysis in stored PBMC
Through study completion, an average of 2 year
Metabolomic profiles
Time Frame: Through study completion, an average of 2 year
The concentration of individual metabolites or cluster of metabolites implicated in amino acid and lipid metabolism
Through study completion, an average of 2 year
Socio-Economical-Psychological (SEP) score
Time Frame: Through study completion, an average of 2 year
Socioeconomic and psychological (perceived social isolation) score, calculated through a dedicated questionnaire
Through study completion, an average of 2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Licia Rivoltini, Fondazione IRCCS Istituto Nazionale Tumori - Milan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 10, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 3, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 11, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 18, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 2, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • INT 48/21

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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