Selective Plasma Adsorption of Extracellular DNA in Prevention of Intraoperative Metastasis in Pancreatic Cancer (Pilot Study)
NCT ID: NCT06967662
Last Updated: 2025-05-16
Study Results
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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ENROLLING_BY_INVITATION
NA
28 participants
INTERVENTIONAL
2025-04-04
2027-04-04
Brief Summary
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* Does selective plasma adsorption of extracellular DNA improve the survival of participants after surgical removal of pancreatic cancer?
* Does selective plasma adsorption of extracellular DNA reduce the risk of the recurrence of pancreatic cancer?
* What medical problems do participants have when they receive selective plasma adsorption of extracellular DNA during surgical removal of pancreatic cancer? Researchers will compare clinical data of participants who had selective plasma adsorption of extracellular DNA and those who did not to see if there are any differences in their health.
Participants who are scheduled for surgical removal of pancreatic cancer by their doctor according to medical indications will:
* Either receive selective plasma adsorption of extracellular DNA during surgical removal of pancreatic cancer and on the next day after the surgery, or not.
* Do blood tests prior to surgery, during the surgery, on the next day after the surgery, one week after the surgery, 3, 6, 9, and 12 months after the surgery.
* Do computed tomography scans 3, 6, 9, and 12 months after the surgery. Participants will receive selective plasma adsorption of extracellular DNA, blood tests, and computed tomography scans for free.
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Detailed Description
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The tumor microenvironment plays a key role in the formation of metastases and in modulating the response to therapy in patients with cancer. It is represented by cancer-associated fibroblasts, as well as a number of infiltrating immune cells, including cancer-associated neutrophils (CAN). CAN make up a significant proportion of all cells surrounding the tumor. It has been shown that an increase in their number is associated with metastases and, in general, a worse prognosis in a number of cancer diseases. Moreover, the neutrophil-to-lymphocyte ratio has found wide clinical application as a predictor of overall and cancer progression-related mortality.
The most studied mechanism of the positive effect of CAN on metastasis and evasion of the immune response is the production of neutrophil extracellular traps (NETs). NETs are web-like structures whose main purpose is to immobilize pathogens (bacteria, fungi, etc.). They consist of chromatin, histones, a number of signaling molecules and antimicrobial peptides. However, in cancer, the ability of NETs to entangle targets, on the contrary, promotes tumor metastasis. It has been shown that NETs surrounding a tumor cell can serve as an adhesive substrate, which mediates the anchoring of metastasis in a new niche. NETs promote the transition of naïve CD4 cells to immunosuppressive regulatory T cells, allowing metastases to further evade immune surveillance. Also, for example, NETs components such as myeloperoxidase promote tumor cell extravasation and metastasis by degrading the extracellular matrix. Co-culture of cancer cells with NETs has been shown to increase the expression of E-cadherin and vimentin, which enhances their migratory capacity.
There is a wealth of data, both in animal models and in patient biomaterial, indicating that elevated NETs levels are associated not only with cancer in general, but also with the presence of metastases. A number of studies have shown that administration of DNase, which cleaves NETs, to animals stops the spread of metastases. Moreover, clinical trials are currently underway on the use of DNase in chemotherapy (NCT00536952, NCT02462265, etc.). It is worth noting that NETs are not the only DNA-containing structures that promote metastasis. There are also cancer extracellular chromatin networks (CECN); In animal models, it has been shown that the introduction of DNase, which affects NETs and CECN, significantly reduces the likelihood of metastasis, while no decrease in the level of circulating tumor cells is observed, indicating a significant modulating role of these DNA structures in the metastasis process. At the same time, it is known that long-term use of DNase leads to a decrease in the overall survival of laboratory animals, which raises the question of when metastasis prevention should be carried out, given the ambiguous safety of this approach.
The dynamics of metastasis formation throughout a patient's life are not completely clear. There is evidence that metastasis can begin almost in parallel with the development of the primary tumor, and in such cases (the frequency of which, unfortunately, cannot be estimated) it is very difficult to influence the development of metastases. At the same time, many researchers note that the most significant (and potentially controllable) moment at which metastases can form is the invasive intervention (biopsy, perhaps to a greater extent - resection). According to the results of dozens of studies in various types of oncological diseases in patients and in animal models, it is noted that invasive intervention is significantly associated with both an increase in the level of circulating tumor cells and the development of metastases (dissemination of cells along the needle or when tumor tissue is damaged; the occurrence of a proinflammatory background that promotes the breakdown of the extracellular matrix and extravasation, etc.).
Thus, there is a need to develop a technology for intraoperative prevention of metastasis formation based on the removal of DNA-containing structures (NETs and CECN) from the bloodstream of patients with pancreatic cancer, for which the use of selective plasma adsorption using the NucleoCor® sorption column might be of great value.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
DOUBLE
Study Groups
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Selective plasma adsorption of extracellular DNA
Patients in this arm will recieve selective plasma adsorption of extracellular DNA during surgical removal of the tumor and on the next day after the srugery.
Selective plasma adsorption of extracellular DNA
Selective plasma adsorption of extracellular DNA using NucleoCor® sorption columns (Pocard Ltd., Russia) on the Spectra Optia™ Apheresis System (Terumo Blood and Cell Technologies, USA). NucleoCor® is a sorption column for plasma adsorption containing porous spherical agarose beads with a ligand that selectively binds extracellular DNA. This medical device has a Registration Certificate No. РЗН 2022/18982 in Russian Federation. Participants will receive selective plasma adsorption of extracellular DNA twice: once during the tumor removal surgery (the procedure will be initiated at the time of pancreatic tumor mobilization and will be stopped an hour after removal of the organ complex) and once on the day after the surgery.
Control (no selective plasma adsorption of extracellular DNA )
Patients in this arm will not recieve selective plasma adsorption of extracellular DNA.
No interventions assigned to this group
Interventions
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Selective plasma adsorption of extracellular DNA
Selective plasma adsorption of extracellular DNA using NucleoCor® sorption columns (Pocard Ltd., Russia) on the Spectra Optia™ Apheresis System (Terumo Blood and Cell Technologies, USA). NucleoCor® is a sorption column for plasma adsorption containing porous spherical agarose beads with a ligand that selectively binds extracellular DNA. This medical device has a Registration Certificate No. РЗН 2022/18982 in Russian Federation. Participants will receive selective plasma adsorption of extracellular DNA twice: once during the tumor removal surgery (the procedure will be initiated at the time of pancreatic tumor mobilization and will be stopped an hour after removal of the organ complex) and once on the day after the surgery.
Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
* General contraindication to plasma adsorption (hypoproteinemia; acute cardiovascular failure; intolerance to foreign protein; decreased (less than 90/60 mm Hg) arterial pressure; gastrointestinal bleeding; acute cerebrovascular accidents; acute anemia; severe hypoxia).
18 Years
75 Years
ALL
No
Sponsors
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POCARD Ltd.
UNKNOWN
University Clinic of Lomonosov Moscow University
UNKNOWN
Ilyinskaya Hospital, JSC
OTHER
Responsible Party
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Locations
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Ilyinskaya Hospital, JSC
Moscow, Moscow Oblast, Russia
Countries
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References
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Zhang L, Jin R, Yang X, Ying D. A population-based study of synchronous distant metastases and prognosis in patients with PDAC at initial diagnosis. Front Oncol. 2023 Jan 26;13:1087700. doi: 10.3389/fonc.2023.1087700. eCollection 2023.
Yang LY, Luo Q, Lu L, Zhu WW, Sun HT, Wei R, Lin ZF, Wang XY, Wang CQ, Lu M, Jia HL, Chen JH, Zhang JB, Qin LX. Increased neutrophil extracellular traps promote metastasis potential of hepatocellular carcinoma via provoking tumorous inflammatory response. J Hematol Oncol. 2020 Jan 6;13(1):3. doi: 10.1186/s13045-019-0836-0.
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Wculek SK, Malanchi I. Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature. 2015 Dec 17;528(7582):413-7. doi: 10.1038/nature16140. Epub 2015 Dec 9.
Wang H, Zhang H, Wang Y, Brown ZJ, Xia Y, Huang Z, Shen C, Hu Z, Beane J, Ansa-Addo EA, Huang H, Tian D, Tsung A. Regulatory T-cell and neutrophil extracellular trap interaction contributes to carcinogenesis in non-alcoholic steatohepatitis. J Hepatol. 2021 Dec;75(6):1271-1283. doi: 10.1016/j.jhep.2021.07.032. Epub 2021 Aug 4.
Ventriglia J, Petrillo A, Huerta Alvaro M, Laterza MM, Savastano B, Gambardella V, Tirino G, Pompella L, Diana A, Iovino F, Troiani T, Martinelli E, Morgillo F, Orditura M, Cervantes A, Ciardiello F, De Vita F. Neutrophil to Lymphocyte Ratio as a Predictor of Poor Prognosis in Metastatic Pancreatic Cancer Patients Treated with Nab-Paclitaxel plus Gemcitabine: A Propensity Score Analysis. Gastroenterol Res Pract. 2018 Jun 10;2018:2373868. doi: 10.1155/2018/2373868. eCollection 2018.
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Shi L, Yao H, Liu Z, Xu M, Tsung A, Wang Y. Endogenous PAD4 in Breast Cancer Cells Mediates Cancer Extracellular Chromatin Network Formation and Promotes Lung Metastasis. Mol Cancer Res. 2020 May;18(5):735-747. doi: 10.1158/1541-7786.MCR-19-0018. Epub 2020 Mar 19.
Seyfried TN, Huysentruyt LC. On the origin of cancer metastasis. Crit Rev Oncog. 2013;18(1-2):43-73. doi: 10.1615/critrevoncog.v18.i1-2.40.
Najmeh S, Cools-Lartigue J, Rayes RF, Gowing S, Vourtzoumis P, Bourdeau F, Giannias B, Berube J, Rousseau S, Ferri LE, Spicer JD. Neutrophil extracellular traps sequester circulating tumor cells via beta1-integrin mediated interactions. Int J Cancer. 2017 May 15;140(10):2321-2330. doi: 10.1002/ijc.30635. Epub 2017 Mar 2.
Monti M, De Rosa V, Iommelli F, Carriero MV, Terlizzi C, Camerlingo R, Belli S, Fonti R, Di Minno G, Del Vecchio S. Neutrophil Extracellular Traps as an Adhesion Substrate for Different Tumor Cells Expressing RGD-Binding Integrins. Int J Mol Sci. 2018 Aug 9;19(8):2350. doi: 10.3390/ijms19082350.
Martin OA, Anderson RL, Narayan K, MacManus MP. Does the mobilization of circulating tumour cells during cancer therapy cause metastasis? Nat Rev Clin Oncol. 2017 Jan;14(1):32-44. doi: 10.1038/nrclinonc.2016.128. Epub 2016 Aug 23.
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Julious, Steven. 2005. "Sample Size of 12 per Group Rule of Thumb for a Pilot Study." Pharmaceutical Statistics 4:287-91. doi: 10.1002/pst.185.
Jain M, Atayan D, Rakhmatullin T, Dakhtler T, Popov P, Kim P, Viborniy M, Gontareva I, Samokhodskaya L, Egorov V. Cell-Free Tumor DNA Detection-Based Liquid Biopsy of Plasma and Bile in Patients with Various Pancreatic Neoplasms. Biomedicines. 2024 Jan 18;12(1):220. doi: 10.3390/biomedicines12010220.
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Other Identifiers
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01/2025
Identifier Type: -
Identifier Source: org_study_id
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