Clincosm LogoSign in Get a demo

SERPENTINE: Quantifying Systemic Immunosuppression to Personalize Cancer Therapy

Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle (Other)
Overall Status
Recruiting
CT.gov ID
NCT04941365
Collaborator
Fondazione IRCCS ISTITUTO NAZIONALE TUMORI (Other)
600
Enrollment
6
Locations
1
Arm
12.8
Anticipated Duration (Months)
100
Patients Per Site
7.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Diagnostic Test: single arm
 N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
600 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
This is a multi-centric prospective observational study, testing whether the blood level of MDSC-related immunosuppression does correlate with clinical outcome (clinical response by RECIST criteria, PFS, DFS) and thus may help predicting sensitivity or resistance to therapy in cancer patients. In addition, blood samples will be extensively studied to gain insights into the molecular and metabolic pathways regulating myeloid-mediated immunosuppression, with the goal of defining novel targets of immunomodulation.This is a multi-centric prospective observational study, testing whether the blood level of MDSC-related immunosuppression does correlate with clinical outcome (clinical response by RECIST criteria, PFS, DFS) and thus may help predicting sensitivity or resistance to therapy in cancer patients. In addition, blood samples will be extensively studied to gain insights into the molecular and metabolic pathways regulating myeloid-mediated immunosuppression, with the goal of defining novel targets of immunomodulation.
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
Quantifying Systemic Immunosuppression to Personalize Cancer Therapy
Actual Study Start Date :
Jul 7, 2022
Anticipated Primary Completion Date :
Aug 1, 2023
Anticipated Study Completion Date :
Aug 1, 2023

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

  1. 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. [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.

Secondary Outcome Measures

  1. discovery and development of an additional MDSC-related blood biomarkers associated with the phenotypic or functional profile of these cells [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

  2. obtention insights into the signaling and metabolic pathways regulating human MDSC, for the discovery of innovative cancer therapeutic targets based on immunomodulation [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

  3. 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 [at the baseline]

    Loneliness Questionnaire (no min and max values)

  4. 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 [at the baseline]

    Socio-Economical Questionnaire (no min and max values)

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

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Tanta University Tanta Egypt 31111
2 ICM Montpellier France 34298
3 German Cancer Research Center Heidelberg Germany 69120
4 ASST Papa Giovanni XXIII Bergamo Italy 24127
5 Fondazione IRCCS ISTITUTO NAZIONALE TUMORI Milan Italy 20133
6 Oslo University Hospital Oslo Norway 0379

Sponsors and Collaborators

  • Institut du Cancer de Montpellier - Val d'Aurelle
  • Fondazione IRCCS ISTITUTO NAZIONALE TUMORI

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Institut du Cancer de Montpellier - Val d'Aurelle
ClinicalTrials.gov Identifier:
NCT04941365
Other Study ID Numbers:
  • PROICM 2021-05 SER
First Posted:
Jun 28, 2021
Last Update Posted:
Aug 4, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Squamous Cell Carcinoma of Head and Neck

Study Results

No Results Posted as of Aug 4, 2022