Quantifying Systemic Immunosuppression to Personalize Cancer Therapy

NCT04941365 | Withdrawn

• 1 other identifier: PROICM 2021-05 SER
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Metastatic Melanoma; Metastatic Breast Cancer; Advanced Renal Cell Carcinoma; Squamous Cell Carcinoma of Head and Neck; Non-small Cell Lung Cancer Stage III; Healthy

Outcome Measures

Primary Outcomes (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.

  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 Outcomes (4)

• 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

• 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

• 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

• 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

Study Arms (1)

single arm

EXPERIMENTAL

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

Interventions

single arm 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).

single arm

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Related Publications (23)

• Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018 Mar 23;359(6382):1350-1355. doi: 10.1126/science.aar4060. Epub 2018 Mar 22.

  PMID: 29567705 BACKGROUND

• Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G. Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents. Cancer Cell. 2015 Dec 14;28(6):690-714. doi: 10.1016/j.ccell.2015.10.012.

  PMID: 26678337 BACKGROUND

• Apetoh L, Tesniere A, Ghiringhelli F, Kroemer G, Zitvogel L. Molecular interactions between dying tumor cells and the innate immune system determine the efficacy of conventional anticancer therapies. Cancer Res. 2008 Jun 1;68(11):4026-30. doi: 10.1158/0008-5472.CAN-08-0427.

  PMID: 18519658 BACKGROUND

• Peguillet I, Milder M, Louis D, Vincent-Salomon A, Dorval T, Piperno-Neumann S, Scholl SM, Lantz O. High numbers of differentiated effector CD4 T cells are found in patients with cancer and correlate with clinical response after neoadjuvant therapy of breast cancer. Cancer Res. 2014 Apr 15;74(8):2204-16. doi: 10.1158/0008-5472.CAN-13-2269. Epub 2014 Feb 17.

  PMID: 24535711 BACKGROUND

• Wilmott JS, Long GV, Howle JR, Haydu LE, Sharma RN, Thompson JF, Kefford RF, Hersey P, Scolyer RA. Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic melanoma. Clin Cancer Res. 2012 Mar 1;18(5):1386-94. doi: 10.1158/1078-0432.CCR-11-2479. Epub 2011 Dec 12.

  PMID: 22156613 BACKGROUND

• Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, Porta-Pardo E, Gao GF, Plaisier CL, Eddy JA, Ziv E, Culhane AC, Paull EO, Sivakumar IKA, Gentles AJ, Malhotra R, Farshidfar F, Colaprico A, Parker JS, Mose LE, Vo NS, Liu J, Liu Y, Rader J, Dhankani V, Reynolds SM, Bowlby R, Califano A, Cherniack AD, Anastassiou D, Bedognetti D, Mokrab Y, Newman AM, Rao A, Chen K, Krasnitz A, Hu H, Malta TM, Noushmehr H, Pedamallu CS, Bullman S, Ojesina AI, Lamb A, Zhou W, Shen H, Choueiri TK, Weinstein JN, Guinney J, Saltz J, Holt RA, Rabkin CS; Cancer Genome Atlas Research Network; Lazar AJ, Serody JS, Demicco EG, Disis ML, Vincent BG, Shmulevich I. The Immune Landscape of Cancer. Immunity. 2018 Apr 17;48(4):812-830.e14. doi: 10.1016/j.immuni.2018.03.023. Epub 2018 Apr 5.

  PMID: 29628290 BACKGROUND

• Spitzer MH, Carmi Y, Reticker-Flynn NE, Kwek SS, Madhireddy D, Martins MM, Gherardini PF, Prestwood TR, Chabon J, Bendall SC, Fong L, Nolan GP, Engleman EG. Systemic Immunity Is Required for Effective Cancer Immunotherapy. Cell. 2017 Jan 26;168(3):487-502.e15. doi: 10.1016/j.cell.2016.12.022. Epub 2017 Jan 19.

  PMID: 28111070 BACKGROUND

• Dumeaux V, Fjukstad B, Fjosne HE, Frantzen JO, Holmen MM, Rodegerdts E, Schlichting E, Borresen-Dale AL, Bongo LA, Lund E, Hallett M. Interactions between the tumor and the blood systemic response of breast cancer patients. PLoS Comput Biol. 2017 Sep 28;13(9):e1005680. doi: 10.1371/journal.pcbi.1005680. eCollection 2017 Sep.

  PMID: 28957325 BACKGROUND

• Cortez-Retamozo V, Etzrodt M, Newton A, Rauch PJ, Chudnovskiy A, Berger C, Ryan RJ, Iwamoto Y, Marinelli B, Gorbatov R, Forghani R, Novobrantseva TI, Koteliansky V, Figueiredo JL, Chen JW, Anderson DG, Nahrendorf M, Swirski FK, Weissleder R, Pittet MJ. Origins of tumor-associated macrophages and neutrophils. Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2491-6. doi: 10.1073/pnas.1113744109. Epub 2012 Jan 30.

  PMID: 22308361 BACKGROUND

• Gabrilovich DI. Myeloid-Derived Suppressor Cells. Cancer Immunol Res. 2017 Jan;5(1):3-8. doi: 10.1158/2326-6066.CIR-16-0297.

  PMID: 28052991 BACKGROUND

• Groth C, Hu X, Weber R, Fleming V, Altevogt P, Utikal J, Umansky V. Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression. Br J Cancer. 2019 Jan;120(1):16-25. doi: 10.1038/s41416-018-0333-1. Epub 2018 Nov 9.

  PMID: 30413826 BACKGROUND

• Ostrand-Rosenberg S. Myeloid derived-suppressor cells: their role in cancer and obesity. Curr Opin Immunol. 2018 Apr;51:68-75. doi: 10.1016/j.coi.2018.03.007. Epub 2018 Mar 13.

  PMID: 29544121 BACKGROUND

• Wesolowski R, Markowitz J, Carson WE 3rd. Myeloid derived suppressor cells - a new therapeutic target in the treatment of cancer. J Immunother Cancer. 2013 Jul 15;1:10. doi: 10.1186/2051-1426-1-10. eCollection 2013.

  PMID: 24829747 BACKGROUND

• Fleming V, Hu X, Weber R, Nagibin V, Groth C, Altevogt P, Utikal J, Umansky V. Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression. Front Immunol. 2018 Mar 2;9:398. doi: 10.3389/fimmu.2018.00398. eCollection 2018.

  PMID: 29552012 BACKGROUND

• Engblom C, Pfirschke C, Pittet MJ. The role of myeloid cells in cancer therapies. Nat Rev Cancer. 2016 Jul;16(7):447-62. doi: 10.1038/nrc.2016.54.

  PMID: 27339708 BACKGROUND

• Filipazzi P, Valenti R, Huber V, Pilla L, Canese P, Iero M, Castelli C, Mariani L, Parmiani G, Rivoltini L. Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol. 2007 Jun 20;25(18):2546-53. doi: 10.1200/JCO.2006.08.5829.

  PMID: 17577033 BACKGROUND

• Filipazzi P, Huber V, Rivoltini L. Phenotype, function and clinical implications of myeloid-derived suppressor cells in cancer patients. Cancer Immunol Immunother. 2012 Feb;61(2):255-263. doi: 10.1007/s00262-011-1161-9. Epub 2011 Nov 27.

  PMID: 22120756 BACKGROUND

• Blattner C, Fleming V, Weber R, Himmelhan B, Altevogt P, Gebhardt C, Schulze TJ, Razon H, Hawila E, Wildbaum G, Utikal J, Karin N, Umansky V. CCR5+ Myeloid-Derived Suppressor Cells Are Enriched and Activated in Melanoma Lesions. Cancer Res. 2018 Jan 1;78(1):157-167. doi: 10.1158/0008-5472.CAN-17-0348. Epub 2017 Oct 31.

  PMID: 29089297 BACKGROUND

• Huber V, Vallacchi V, Fleming V, Hu X, Cova A, Dugo M, Shahaj E, Sulsenti R, Vergani E, Filipazzi P, De Laurentiis A, Lalli L, Di Guardo L, Patuzzo R, Vergani B, Casiraghi E, Cossa M, Gualeni A, Bollati V, Arienti F, De Braud F, Mariani L, Villa A, Altevogt P, Umansky V, Rodolfo M, Rivoltini L. Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma. J Clin Invest. 2018 Dec 3;128(12):5505-5516. doi: 10.1172/JCI98060. Epub 2018 Nov 5.

  PMID: 30260323 BACKGROUND

• Bronte V, Brandau S, Chen SH, Colombo MP, Frey AB, Greten TF, Mandruzzato S, Murray PJ, Ochoa A, Ostrand-Rosenberg S, Rodriguez PC, Sica A, Umansky V, Vonderheide RH, Gabrilovich DI. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun. 2016 Jul 6;7:12150. doi: 10.1038/ncomms12150.

  PMID: 27381735 BACKGROUND

• De Henau O, Rausch M, Winkler D, Campesato LF, Liu C, Cymerman DH, Budhu S, Ghosh A, Pink M, Tchaicha J, Douglas M, Tibbitts T, Sharma S, Proctor J, Kosmider N, White K, Stern H, Soglia J, Adams J, Palombella VJ, McGovern K, Kutok JL, Wolchok JD, Merghoub T. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kgamma in myeloid cells. Nature. 2016 Nov 17;539(7629):443-447. doi: 10.1038/nature20554. Epub 2016 Nov 9.

  PMID: 27828943 BACKGROUND

• Welters MJ, van der Sluis TC, van Meir H, Loof NM, van Ham VJ, van Duikeren S, Santegoets SJ, Arens R, de Kam ML, Cohen AF, van Poelgeest MI, Kenter GG, Kroep JR, Burggraaf J, Melief CJ, van der Burg SH. Vaccination during myeloid cell depletion by cancer chemotherapy fosters robust T cell responses. Sci Transl Med. 2016 Apr 13;8(334):334ra52. doi: 10.1126/scitranslmed.aad8307.

  PMID: 27075626 BACKGROUND

• Crunkhorn S. Cancer: New path to improving immunotherapy. Nat Rev Drug Discov. 2018 Mar;17(3):164. doi: 10.1038/nrd.2018.22. Epub 2018 Feb 16. No abstract available.

  PMID: 29449711 BACKGROUND

MeSH Terms

Conditions

Melanoma; Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Breast Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: June 28, 2021
• Study Start: July 7, 2022
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: December 22, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share