Quantifying Systemic Immunosuppression to Personalize Cancer Therapy (SERPENTINE)

December 20, 2022 updated by: Institut du Cancer de Montpellier - Val d'Aurelle
It is nowadays well established that the immune system can profoundly influence disease outcome in cancer patients. Increasing evidence is indeed showing that patients displaying spontaneous T cell-mediated immune response against their tumor (defined as immune surveillance) have higher chance to respond to therapies and display globally better prognosis. Conversely, patients whose tumor is characterized by immunosuppression, usually involving myeloid cells and chronic inflammation pathways, often undergo rapid progression and rarely benefit from therapy. Hence, capturing the immune features of individual tumors can help to predict disease course and tailor the therapeutic workup in clinical setting.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

It is nowadays well established that the immune system can profoundly influence disease outcome in cancer patients. Increasing evidence is indeed showing that patients displaying spontaneous T cell-mediated immune response against their tumor (defined as immune surveillance) have higher chance to respond to therapies and display globally better prognosis. Conversely, patients whose tumor is characterized by immunosuppression, usually involving myeloid cells and chronic inflammation pathways, often undergo rapid progression and rarely benefit from therapy. Hence, capturing the immune features of individual tumors can help to predict disease course and tailor the therapeutic workup in clinical setting. In addition, overcoming cancer-related immunosuppression could provide a valid tool to rescue immune surveillance and implement cancer treatment through the engagement of the immunological control.

Delivering the right cure to the right patient is the base of precision medicine, and intensive efforts are ongoing worldwide to include the assessment of immune features unto individual patient profiling. However, despite the enormous amount of preclinical and clinical data proving the pivotal role of immunity in molding disease outcome, the immune-related assays that have been introduced into clinical practice, are still scantly. One major limitation is related to the fact that most immune biomarkers have been so far evaluated at tumor site, which implies the need for tumor biopsies and limitations related to intra-lesion heterogeneity. Instead, tests relying on blood samples are easier to perform, more reliable in terms of reproducibility, and repeatable for longitudinal studies. Of note, it is nowadays well established that cancer immunity is a systemic process involving different peripheral immune organs (lymph nodes, bone marrow and spleen) and, as such, it can be measured in blood. Hence, circulating immune cells might represent an informative source of biomarkers to reveal the type and activation status of immunity at single patient level. This holds particularly true for tumor-related immunosuppression, which is mostly mediated myeloid cells and it is responsible for blunting antitumor T cell immune-surveillance. Early during carcinogenesis, cancer cells establish a tight cross-talk with the bone marrow, mediated by tumor-released soluble factors that influence myelopoiesis. This process results in the introduction into the peripheral circulation, of aberrant immunosuppressive myeloid cells, globally known as Myeloid-Derived Suppressor Cells (MDSC). MDSC are among the most potent allies of the tumor cells, whose growth and progression in vivo in favored by MDSC ability to inhibit antitumor T cells, promote angiogenesis and sustain metastatic spread. High numbers of MDSC in blood and tumor site of cancer patients is reproducibly associated with poor prognosis and resistance to therapy, including immunotherapy. Studies in preclinical models have also shown that in vivo removal of MDSC reduces tumor expansion in vivo and confers sensitivity to treatment including immunotherapy, indicating a promising role of these cells as appealing novel therapeutic target in cancer. Unfortunately, the phenotypic and functional features of human MDSC are still poorly understood and need to be extensively investigated in clinical setting.

The members of the SERPENTINE Consortium have substantially contributed to the discovery and the study of MDSC in cancer, acquiring deep knowledge on the phenotypic and functional features of these cells both in human and murine setting. In the present trial? coordinators are committed to translate the predictive/prognostic role of MDSC immune profiling into real-life clinical practice. Through the concerted effort of all Consortium members and the prospective enrolment of blood samples from a comprehensive cancer patients case set, coordinators are going to develop off-the-shelf predictive/prognostic test based on the standardized quantification of MDSC in peripheral blood of cancer patients. In addition, thanks to our multiple expertise, coordinators are going to get deep insights into the biology of human cancer-related MDSC, for the development of novel therapeutic approaches based on rescuing tumor immune surveillance by antagonizing immunosuppression.

Study Type

Interventional

Phase

  • Not Applicable

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

Ages Eligible for Study

14 years to 86 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

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 enrolling 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

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: single arm
Blood samples will be collected at baseline(Visit 1), and during therapy at visit 2 (around one month after the treatment starting) and at Visit 3 (around three months after the treatment starting. And, optionally, in case of a disease progression (PD).
Diagnostic test: single arm
Blood samples will be collected at baseline(Visit 1), and during therapy at visit 2 (around one month after the treatment starting) and at Visit 3 (around three months after the treatment starting. And, optionally, in case of a disease progression (PD).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Investigation of whether a flow cytometry blood-based MDSC quantification assay, does predict disease course in different cancer patients undergoing standard therapies including immunotherapy, chemotherapy, target therapies and surgery.
Time Frame: during 3 months after the start of the treatment
Correlation of myeloid-related blood biomarkers (including quantification of myeloid cell subsets in peripheral blood mononuclear cells and whole blood) with disease outcome including objective response to therapy, progression-free survival and overall survival, to identify tool for predicting resistance to treatment and poor prognosis.
during 3 months after the start of the treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
discovery and development of an additional MDSC-related blood biomarkers associated with the phenotypic or functional profile of these cells
Time Frame: during 3 months after the start of the treatment
Transcriptional signatures identified on PBMC and sorted myeloid cells form whole blood, at baseline or first evaluation
during 3 months after the start of the treatment
obtention insights into the signaling and metabolic pathways regulating human MDSC, for the discovery of innovative cancer therapeutic targets based on immunomodulation
Time Frame: during 3 months after the start of the treatment
Metabolomic profiles, as defined by the concentration of individual metabolites or cluster of metabolites implicated in amino acid and lipid metabolism
during 3 months after the start of the treatment
perform the first survey assessing the link between MDSC (myeloid-derived suppressor cells) immunosuppression and patient psychological traits, including socio-economical status and perceived social isolation
Time Frame: at the baseline
Loneliness Questionnaire (no min and max values)
at the baseline
perform the first survey assessing the link between MDSC (myeloid-derived suppressor cells) immunosuppression and patient psychological traits, including socio-economical status and perceived social isolation
Time Frame: at the baseline
Socio-Economical Questionnaire (no min and max values)
at the baseline

Collaborators and Investigators

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

Sponsor

Institut du Cancer de Montpellier - Val d'Aurelle

Collaborators

Fondazione IRCCS ISTITUTO NAZIONALE TUMORI

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)

July 7, 2022

Primary Completion (Anticipated)

March 1, 2024

Study Completion (Anticipated)

March 1, 2024

Study Registration Dates

First Submitted

June 11, 2021

First Submitted That Met QC Criteria

June 25, 2021

First Posted (Actual)

June 28, 2021

Study Record Updates

Last Update Posted (Estimate)

December 22, 2022

Last Update Submitted That Met QC Criteria

December 20, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PROICM 2021-05 SER

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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