Clincosm LogoSign in Get a demo

Serpentine: Quantifying Systemic Immunosuppression to Personalize Cancer Therapy

Sponsor
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano (Other)
Overall Status
Recruiting
CT.gov ID
NCT05621837
Collaborator
(none)
1,000
Enrollment
1
Location
26.3
Anticipated Duration (Months)
38.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Other: MDSC quantification

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 Design

Study Type:
Observational
Anticipated Enrollment :
1000 participants
Observational Model:
Case-Control
Time Perspective:
Prospective
Official Title:
Quantifying Systemic Immunosuppression to Personalize Cancer Therapy
Actual Study Start Date :
Mar 10, 2022
Anticipated Primary Completion Date :
May 17, 2024
Anticipated Study Completion Date :
May 17, 2024

Arms and Interventions

Arm Intervention/Treatment
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).

Outcome Measures

Primary Outcome Measures

  1. 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

  2. Immunological endpoint [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

  3. Immunological endpoint [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

  4. Immunological endpoint [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

  5. Clinical endpoint_PFS [Through study completion, an average of 2 year]

    Progression-Free Survival (PFS)

  6. Clinical endpoint_OS [Through study completion, an average of 2 year]

    Overall Survival (OS)

  7. Clinical endpoint_ORR [Through study completion, an average of 2 year]

    Overall Response Rate (ORR)

Secondary Outcome Measures

  1. Myeloid Index Score (MIS) [Through study completion, an average of 2 year]

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

  2. Index score values [Through study completion, an average of 2 year]

    Index score values on plasma cytokine concentration or MDSC-miRs

  3. 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

  4. 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

  5. Phospho-kinome signature result [Through study completion, an average of 2 year]

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

  6. 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

  7. 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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 90 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy 20033

Sponsors and Collaborators

  • Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Investigators

  • Principal Investigator: Licia Rivoltini, Fondazione IRCCS Istituto Nazionale Tumori - Milan

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
ClinicalTrials.gov Identifier:
NCT05621837
Other Study ID Numbers:
  • INT 48/21
First Posted:
Nov 18, 2022
Last Update Posted:
Nov 18, 2022
Last Verified:
Sep 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Renal Cell
Squamous Cell Carcinoma of Head and Neck
Carcinoma, Small Cell
Small Cell Lung Carcinoma

Study Results

No Results Posted as of Nov 18, 2022