Quantifying Systemic Immunosuppression to Personalize Cancer Therapy
NCT ID: NCT04941365
Last Updated: 2022-12-22
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
WITHDRAWN
Clinical Phase
NA
Study Classification
INTERVENTIONAL
Study Start Date
2022-07-07
Study Completion Date
2024-03-31
Brief Summary
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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
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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.
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.
Conditions
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Metastatic Melanoma
Metastatic Breast Cancer
Advanced Renal Cell Carcinoma
Squamous Cell Carcinoma of Head and Neck
Non-small Cell Lung Cancer Stage III
Healthy
Study Design
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Allocation Method
NA
Intervention Model
SINGLE_GROUP
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.
Primary Study Purpose
DIAGNOSTIC
Blinding Strategy
NONE
Study Groups
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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).
Group Type
EXPERIMENTAL
single arm
Intervention Type
DIAGNOSTIC_TEST
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).
Interventions
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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).
Intervention Type
DIAGNOSTIC_TEST
Eligibility Criteria
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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
* 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
* 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
Minimum Eligible Age
18 Years
Maximum Eligible Age
90 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
Yes
Sponsors
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Fondazione IRCCS ISTITUTO NAZIONALE TUMORI
UNKNOWN
Sponsor Role
collaborator
Institut du Cancer de Montpellier - Val d'Aurelle
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Countries
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Egypt
France
Germany
Italy
Norway
References
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Other Identifiers
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PROICM 2021-05 SER
Identifier Type: -
Identifier Source: org_study_id