Quantifying Systemic Immunosuppression to Personalize Cancer Therapy (SERPENTINE)
Primary Purpose
Metastatic Melanoma, Metastatic Breast Cancer, Advanced Renal Cell Carcinoma
Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
single arm
Sponsored by
About this trial
This is an interventional diagnostic trial for Metastatic Melanoma
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
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
single arm
Arm Description
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).
Outcomes
Primary Outcome Measures
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.
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
discovery and development of an additional MDSC-related blood biomarkers associated with the phenotypic or functional profile of these cells
Transcriptional signatures identified on PBMC and sorted myeloid cells form whole blood, at baseline or first evaluation
obtention insights into the signaling and metabolic pathways regulating human MDSC, for the discovery of innovative cancer therapeutic targets based on immunomodulation
Metabolomic profiles, as defined by the concentration of individual metabolites or cluster of metabolites implicated in amino acid and lipid metabolism
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
Loneliness Questionnaire (no min and max values)
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
Socio-Economical Questionnaire (no min and max values)
Full Information
NCT ID
NCT04941365
First Posted
June 11, 2021
Last Updated
December 20, 2022
Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle
Collaborators
Fondazione IRCCS ISTITUTO NAZIONALE TUMORI
1. Study Identification
Unique Protocol Identification Number
NCT04941365
Brief Title
Quantifying Systemic Immunosuppression to Personalize Cancer Therapy
Acronym
SERPENTINE
Official Title
Quantifying Systemic Immunosuppression to Personalize Cancer Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Withdrawn
Why Stopped
please refer to NCT05621837
Study Start Date
July 7, 2022 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle
Collaborators
Fondazione IRCCS ISTITUTO NAZIONALE TUMORI
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Melanoma, Metastatic Breast Cancer, Advanced Renal Cell Carcinoma, Squamous Cell Carcinoma of Head and Neck, Non-small Cell Lung Cancer Stage III, Healthy
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
single arm
Arm Type
Experimental
Arm Description
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).
Intervention Type
Diagnostic Test
Intervention Name(s)
single arm
Intervention Description
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).
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
during 3 months after the start of the treatment
Secondary Outcome Measure Information:
Title
discovery and development of an additional MDSC-related blood biomarkers associated with the phenotypic or functional profile of these cells
Description
Transcriptional signatures identified on PBMC and sorted myeloid cells form whole blood, at baseline or first evaluation
Time Frame
during 3 months after the start of the treatment
Title
obtention insights into the signaling and metabolic pathways regulating human MDSC, for the discovery of innovative cancer therapeutic targets based on immunomodulation
Description
Metabolomic profiles, as defined by the concentration of individual metabolites or cluster of metabolites implicated in amino acid and lipid metabolism
Time Frame
during 3 months after the start of the treatment
Title
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
Description
Loneliness Questionnaire (no min and max values)
Time Frame
at the baseline
Title
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
Description
Socio-Economical Questionnaire (no min and max values)
Time Frame
at the baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
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
12. IPD Sharing Statement
Plan to Share IPD
No
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Quantifying Systemic Immunosuppression to Personalize Cancer Therapy
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