Nctid:
NCT06611072
Payload:
{"hasResults"=>false, "derivedSection"=>{"miscInfoModule"=>{"versionHolder"=>"2024-10-04"}, "conditionBrowseModule"=>{"meshes"=>[{"id"=>"D000010051", "term"=>"Ovarian Neoplasms"}, {"id"=>"D000077216", "term"=>"Carcinoma, Ovarian Epithelial"}, {"id"=>"D000014786", "term"=>"Vision Disorders"}], "ancestors"=>[{"id"=>"D000004701", "term"=>"Endocrine Gland Neoplasms"}, {"id"=>"D000009371", "term"=>"Neoplasms by Site"}, {"id"=>"D000009369", "term"=>"Neoplasms"}, {"id"=>"D000010049", "term"=>"Ovarian Diseases"}, {"id"=>"D000000291", "term"=>"Adnexal Diseases"}, {"id"=>"D000005831", "term"=>"Genital Diseases, Female"}, {"id"=>"D000052776", "term"=>"Female Urogenital Diseases"}, {"id"=>"D000005261", "term"=>"Female Urogenital Diseases and Pregnancy Complications"}, {"id"=>"D000091642", "term"=>"Urogenital Diseases"}, {"id"=>"D000005833", "term"=>"Genital Neoplasms, Female"}, {"id"=>"D000014565", "term"=>"Urogenital Neoplasms"}, {"id"=>"D000091662", "term"=>"Genital Diseases"}, {"id"=>"D000004700", "term"=>"Endocrine System Diseases"}, {"id"=>"D000006058", "term"=>"Gonadal Disorders"}, {"id"=>"D000002277", "term"=>"Carcinoma"}, {"id"=>"D000009375", "term"=>"Neoplasms, Glandular and Epithelial"}, {"id"=>"D000009370", "term"=>"Neoplasms by Histologic Type"}, {"id"=>"D000012678", "term"=>"Sensation Disorders"}, {"id"=>"D000009461", "term"=>"Neurologic Manifestations"}, {"id"=>"D000009422", "term"=>"Nervous System Diseases"}, {"id"=>"D000005128", "term"=>"Eye Diseases"}], "browseLeaves"=>[{"id"=>"M5534", "name"=>"Carcinoma", "relevance"=>"LOW"}, {"id"=>"M12974", "name"=>"Ovarian Neoplasms", "asFound"=>"Ovarian Cancer", "relevance"=>"HIGH"}, {"id"=>"M1704", "name"=>"Carcinoma, Ovarian Epithelial", "asFound"=>"Ovarian Cancer", "relevance"=>"HIGH"}, {"id"=>"M17530", "name"=>"Vision Disorders", "asFound"=>"Suppression", "relevance"=>"HIGH"}, {"id"=>"M7863", "name"=>"Endocrine Gland Neoplasms", "relevance"=>"LOW"}, {"id"=>"M12972", "name"=>"Ovarian Diseases", "relevance"=>"LOW"}, {"id"=>"M3643", "name"=>"Adnexal Diseases", "relevance"=>"LOW"}, {"id"=>"M2876", "name"=>"Genital Diseases", "relevance"=>"LOW"}, {"id"=>"M8943", "name"=>"Genital Diseases, Female", "relevance"=>"LOW"}, {"id"=>"M2875", "name"=>"Urogenital Diseases", "relevance"=>"LOW"}, {"id"=>"M27093", "name"=>"Female Urogenital Diseases", "relevance"=>"LOW"}, {"id"=>"M14127", "name"=>"Pregnancy Complications", "relevance"=>"LOW"}, {"id"=>"M8399", "name"=>"Female Urogenital Diseases and Pregnancy Complications", "relevance"=>"LOW"}, {"id"=>"M8945", "name"=>"Genital Neoplasms, Female", "relevance"=>"LOW"}, {"id"=>"M17315", "name"=>"Urogenital Neoplasms", "relevance"=>"LOW"}, {"id"=>"M7862", "name"=>"Endocrine System Diseases", "relevance"=>"LOW"}, {"id"=>"M9163", "name"=>"Gonadal Disorders", "relevance"=>"LOW"}, {"id"=>"M12320", "name"=>"Neoplasms, Glandular and Epithelial", "relevance"=>"LOW"}, {"id"=>"M12315", "name"=>"Neoplasms by Histologic Type", "relevance"=>"LOW"}, {"id"=>"M15490", "name"=>"Sensation Disorders", "relevance"=>"LOW"}, {"id"=>"M12404", "name"=>"Neurologic Manifestations", "relevance"=>"LOW"}, {"id"=>"M8271", "name"=>"Eye Diseases", "relevance"=>"LOW"}, {"id"=>"T4352", "name"=>"Ovarian Cancer", "asFound"=>"Ovarian Cancer", "relevance"=>"HIGH"}, {"id"=>"T4354", "name"=>"Ovarian Epithelial Cancer", "asFound"=>"Ovarian Cancer", "relevance"=>"HIGH"}], "browseBranches"=>[{"name"=>"Neoplasms", "abbrev"=>"BC04"}, {"name"=>"All Conditions", "abbrev"=>"All"}, {"name"=>"Urinary Tract, Sexual Organs, and Pregnancy Conditions", "abbrev"=>"BXS"}, {"name"=>"Gland and Hormone Related Diseases", "abbrev"=>"BC19"}, {"name"=>"Nervous System Diseases", "abbrev"=>"BC10"}, {"name"=>"Eye Diseases", "abbrev"=>"BC11"}, {"name"=>"Symptoms and General Pathology", "abbrev"=>"BC23"}, {"name"=>"Rare Diseases", "abbrev"=>"Rare"}]}, "interventionBrowseModule"=>{"browseLeaves"=>[{"id"=>"M2853", "name"=>"Immunomodulating Agents", "relevance"=>"LOW"}], "browseBranches"=>[{"name"=>"All Drugs and Chemicals", "abbrev"=>"All"}]}}, "protocolSection"=>{"designModule"=>{"phases"=>["NA"], "studyType"=>"INTERVENTIONAL", "designInfo"=>{"allocation"=>"NON_RANDOMIZED", "maskingInfo"=>{"masking"=>"NONE"}, "primaryPurpose"=>"OTHER", "interventionModel"=>"PARALLEL", "interventionModelDescription"=>"investigator-initiated, multi-center explorative cross-sectional study"}, "enrollmentInfo"=>{"type"=>"ESTIMATED", "count"=>90}}, "statusModule"=>{"overallStatus"=>"NOT_YET_RECRUITING", "startDateStruct"=>{"date"=>"2025-01", "type"=>"ESTIMATED"}, "expandedAccessInfo"=>{"hasExpandedAccess"=>false}, "statusVerifiedDate"=>"2024-09", "completionDateStruct"=>{"date"=>"2027-12", "type"=>"ESTIMATED"}, "lastUpdateSubmitDate"=>"2024-09-23", "studyFirstSubmitDate"=>"2024-08-04", "studyFirstSubmitQcDate"=>"2024-09-23", "lastUpdatePostDateStruct"=>{"date"=>"2024-09-24", "type"=>"ACTUAL"}, "studyFirstPostDateStruct"=>{"date"=>"2024-09-24", "type"=>"ACTUAL"}, "primaryCompletionDateStruct"=>{"date"=>"2027-10", "type"=>"ESTIMATED"}}, "outcomesModule"=>{"primaryOutcomes"=>[{"measure"=>"Cell composition of immune organs using flow cytometry", "timeFrame"=>"3 years including evaluation phase", "description"=>"The number and ratios of different types of stem and immune cells will be determined using general cell protein markers in combination with flow cytometry. Analysis will be performed on blood, spleen, bone marrow and the intraperitoneal fluid."}, {"measure"=>"Cell composition and epigenetic status of cells of immune organs using ATAC and RNA sequencing", "timeFrame"=>"3 years including evaluation phase", "description"=>"Cell ratios and epigenetic profile of immune cells in the blood, tumor, bone marrow, and spleen will be analyzed using single-cell RNA and single-cell ATAC sequencing."}]}, "oversightModule"=>{"isUsExport"=>false, "oversightHasDmc"=>false, "isFdaRegulatedDrug"=>false, "isFdaRegulatedDevice"=>false}, "conditionsModule"=>{"keywords"=>["Ovarian cancer", "Immune system", "Immune suppression", "Immune system suppression", "Immunotherapy", "Monocytes", "Myeloid cells", "Vena punction", "Bone marrow aspiration", "Spleen biopsy", "Peritoneal fluid", "Tumor biopsy"], "conditions"=>["Ovarian Neoplasms", "Ovarian Cancer", "Ovarian Carcinoma", "Immune Suppression", "Immune System Suppression"]}, "descriptionModule"=>{"briefSummary"=>"The goal of this multi-center explorative cross-sectional study is to characterize and phenotype the immune state of ovarian cancer (OC) patients compared to controls without cancer, thereby focusing on the hematopoietic organs and the immune cells originating from these organs. This will be executed by assessing the transcriptional, epigenetic, and functional programming of circulating monocytes and myeloid progenitor cells in OC.\n\nIt is hypothesized that OC and its progression are heavily influenced by myeloid cells and their progenitors, mainly through defective trained immunity responses. It is hypothesized that OC patients suffer from a suppressive trained immunity phenotype.\n\nResearchers will compare (1) patients with OC who undergo primary debulking surgery and (2) patients with OC who undergo interval debulking surgery to (3) controls as blood and bone marrow donors to see if there are differences between the transcriptional, epigenetic, and functional signature of i) circulating and intra-abdominal monocytes and ii) bone marrow and spleen myeloid progenitor cells.\n\nParticipants will get a:\n\n* Vena puncture\n* Bone marrow aspiration\n* Tumor biopsy (only cases)\n* Spleen biopsy (only cases)\n\nFurthermore, peritoneal fluid will be sent for analysis in all patients.", "detailedDescription"=>"DESCRIPTION OF THE PROBLEM\n\nOvarian cancer (OC) is one of the most lethal cancers due to late-stage of disease at diagnosis. Standard therapy consists of debulking surgery and chemotherapy. However, despite this aggressive treatment, recurrent disease almost invariably occurs resulting in a five-year survival rate of approximately 30%. Immunotherapy could be a way to increase survival in OC patients. However, a major barrier to a successful deployment of cancer immunotherapy for ovarian cancer patients is the immunosuppressive tumor microenvironment.\n\nRESEARCH DIRECTION\n\nTumor-related inflammation is one of the hallmarks of cancers in general. Innate immunity specifically is a common denominator that is involved in the pathogenesis of OC. To improve the patient's outcome and identify novel therapeutic targets, one needs a deeper understanding of the tumor-induced changes in the bone marrow myeloid progenitor cells.\n\nHYPOTHESIS\n\nIt is hypothesized that OC and its progression are heavily influenced by myeloid cells and their progenitors, mainly through defective trained immunity responses. It is hypothesized that OC patients suffer from a suppressive trained immunity phenotype. In the future, therapeutic targeting of trained immunity could be explored to develop novel immunotherapies for tumors that are refractory to conventional treatment.\n\nOBJECTIVE\n\nTo characterize and phenotype the immune state of OC patients compared to controls without cancer, thereby focusing on the hematopoietic organs and the immune cells originating from these organs.\n\nThis will be executed by assessing the transcriptional, epigenetic, and functional programming of circulating monocytes and myeloid progenitor cells in OC.\n\nSTUDY DESIGN\n\nInvestigator-initiated, multi-center explorative cross-sectional study at the Catharina hospital Eindhoven, Radboud University Medical Center and Eindhoven University of Technology.\n\nSTUDY POPULATION\n\nThe following patients will be included in the study:\n\n* Group 1. Patients with OC who undergo primary debulking surgery (N=30)\n* Group 2. Patients with OC who undergo interval debulking surgery (N=30)\n* Group 3. Controls as blood and bone marrow donors (N=30)\n\nMAIN STUDY PARAMETERS/ENDPOINTS\n\nPrimary endpoints: transcriptional, epigenetic, and functional signature of circulating monocytes and myeloid progenitors. For transcriptional markers, differentially expressed genes between the different groups will be the focus, with a particular emphasis on antigen presentation and processing pathways, inflammatory pathways (e.g., NF-kB), metabolic pathways and enzymes, and pattern-recognition receptor (PRR) signal transduction. For epigenetic markers, the focus will be on three histone marks positively associated with gene expression and trained immunity: H3K4me3, which marks promoters; H3K4me1, which marks distal regulatory elements (enhancers); and H3K27ac, which marks active promoters and enhancers. For functional markers, the focus will be on the degree of trained immunity response in vitro."}, "eligibilityModule"=>{"sex"=>"FEMALE", "stdAges"=>["ADULT", "OLDER_ADULT"], "minimumAge"=>"18 years", "healthyVolunteers"=>true, "eligibilityCriteria"=>"Inclusion Criteria:\n\n* Subjects should be at least 18 years old and mentally competent;\n* Newly diagnosed patients with OC who go for primary debulking surgery or patients with OC who are scheduled for interval debulking;\n* Controls: women who undergo surgery for benign gynaecological conditions under general anaesthesia.\n\nExclusion Criteria:\n\n* Mentally incompetent;\n* Pregnant or breastfeeding;\n* Known inflammatory of infectious diseases or an immunosuppressive status;\n* Using medication interfering with the immune system;\n* Severe comorbidities: other active malignancy (except for basal cell carcinoma and other in situ carcinomas);\n* Serious psychiatric pathology;\n* A self reported alcohol consumption of \\>21 units per week."}, "identificationModule"=>{"nctId"=>"NCT06611072", "acronym"=>"ACTION", "briefTitle"=>"ACTivating the Immune Response in Ovarian CaNcer", "organization"=>{"class"=>"OTHER", "fullName"=>"Gynaecologisch Oncologisch Centrum Zuid"}, "officialTitle"=>"Activating the Immune Response in Ovarian Cancer (ACTION) Study", "orgStudyIdInfo"=>{"id"=>"NL86399.015.24"}}, "armsInterventionsModule"=>{"armGroups"=>[{"type"=>"EXPERIMENTAL", "label"=>"Group 1", "description"=>"Patients with OC who undergo primary debulking surgery", "interventionNames"=>["Procedure: Bone marrow aspiration", "Procedure: Vena puncture", "Procedure: Peritoneal fluid", "Procedure: Spleen biopsy", "Procedure: Tumor biopsy"]}, {"type"=>"EXPERIMENTAL", "label"=>"Group 2", "description"=>"Patients with OC who undergo interval debulking surgery", "interventionNames"=>["Procedure: Bone marrow aspiration", "Procedure: Vena puncture", "Procedure: Peritoneal fluid", "Procedure: Spleen biopsy", "Procedure: Tumor biopsy"]}, {"type"=>"ACTIVE_COMPARATOR", "label"=>"Group 3", "description"=>"Controls as blood and bone marrow donors", "interventionNames"=>["Procedure: Bone marrow aspiration", "Procedure: Vena puncture", "Procedure: Peritoneal fluid"]}], "interventions"=>[{"name"=>"Bone marrow aspiration", "type"=>"PROCEDURE", "description"=>"Bone marrow samples (40 ml) will be obtained from the sternum or the iliac crest according to standard practice by experienced operators during the surgery patients will undergo as part of their medical treatment. BM mononuclear cells will be isolated using Ficoll-Paque and progenitor cells will be enriched using positive selection with CD34 beads by MACS. Progenitor cell composition will be identified using flow cytometry. HSPC proliferation assays (standard CFU assays) to assess myeloid colony-forming potential will be performed. In addition, single-cell RNA- sequencing and epigenetic assessment (ATAC-seq, ChIP-seq, DNA methylation) will be performed.", "armGroupLabels"=>["Group 1", "Group 2", "Group 3"]}, {"name"=>"Vena puncture", "type"=>"PROCEDURE", "description"=>"Whole blood (60 ml) will be collected and peripheral blood mononuclear cells (PBMC) will be isolated using Ficoll-Paque. Cellular subpopulations will be purified using negative selection of monocytes with PanMonocyte beads by MACS.", "armGroupLabels"=>["Group 1", "Group 2", "Group 3"]}, {"name"=>"Peritoneal fluid", "type"=>"PROCEDURE", "description"=>"Peritoneal fluid will be collected during the surgery.", "armGroupLabels"=>["Group 1", "Group 2", "Group 3"]}, {"name"=>"Spleen biopsy", "type"=>"PROCEDURE", "description"=>"Spleen samples will be obtained by experienced surgeons during the debulking surgery. Spleen mononuclear cells will be isolated using Ficoll-Paque and progenitor cells will be enriched using positive selection with CD34 beads by MACS. Cellular subpopulations will be further purified using negative selection of monocytes with PanMonocyte beads by MACS. Progenitor cell composition will be identified using flow cytometry. HSPC proliferation assays (standard CFU assays) to assess myeloid colony-forming potential will be performed. In addition, single- cell RNA-sequencing and epigenetic assessment (ATAC-seq, ChIP-seq, DNA methylation) will be performed.", "armGroupLabels"=>["Group 1", "Group 2"]}, {"name"=>"Tumor biopsy", "type"=>"PROCEDURE", "description"=>"During debulking surgery, all visible tumor tissue will be removed by experienced surgeons.", "armGroupLabels"=>["Group 1", "Group 2"]}]}, "contactsLocationsModule"=>{"locations"=>[{"zip"=>"5623EJ", "city"=>"Eindhoven", "state"=>"Brabant", "country"=>"Netherlands", "facility"=>"Catharina Hospital", "geoPoint"=>{"lat"=>51.44083, "lon"=>5.47778}}], "centralContacts"=>[{"name"=>"Jurgen Piek, MD, PhD", "role"=>"CONTACT", "email"=>"jurgen.piek@catharinaziekenhuis.nl", "phone"=>"00310402399300"}, {"name"=>"Noortje Voeten, MD", "role"=>"CONTACT", "email"=>"noortje.voeten@catharinaziekenhuis.nl", "phone"=>"00310402399300"}]}, "ipdSharingStatementModule"=>{"ipdSharing"=>"NO"}, "sponsorCollaboratorsModule"=>{"leadSponsor"=>{"name"=>"Gynaecologisch Oncologisch Centrum Zuid", "class"=>"OTHER"}, "collaborators"=>[{"name"=>"Eindhoven University of Technology", "class"=>"OTHER"}, {"name"=>"Radboud University Medical Center", "class"=>"OTHER"}], "responsibleParty"=>{"type"=>"PRINCIPAL_INVESTIGATOR", "investigatorTitle"=>"MD, PhD", "investigatorFullName"=>"Jurgen M.J. Piek", "investigatorAffiliation"=>"Gynaecologisch Oncologisch Centrum Zuid"}}}}
