Ignite Creation Date:
2025-12-24 @ 7:46 PM
Ignite Modification Date:
2026-01-02 @ 4:24 AM
Study NCT ID:
NCT07124403
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-09-17
First Post:
2025-07-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
DESIR. Evaluation of the Pre-therapeutic Activity of Dihydropyrimidine dEShydrogenase (DPD) in Patients With Cancer and/or Renal Failure
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D051437', 'term': 'Renal Insufficiency'}, {'id': 'D005770', 'term': 'Gastrointestinal Neoplasms'}, {'id': 'D001943', 'term': 'Breast Neoplasms'}], 'ancestors': [{'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D001941', 'term': 'Breast Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001800', 'term': 'Blood Specimen Collection'}], 'ancestors': [{'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_ONLY'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 742}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-09', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2028-09', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-09-11', 'studyFirstSubmitDate': '2025-07-04', 'studyFirstSubmitQcDate': '2025-08-08', 'lastUpdatePostDateStruct': {'date': '2025-09-17', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-08-15', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-03', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'DPD Activity measurement in blood', 'timeFrame': '3 years', 'description': 'DPD Activity is assessed in PBMC in µmole of 5FUH2 / h / 1 million cells'}, {'measure': 'Uracilemia in plasma', 'timeFrame': '3 years', 'description': 'Uracilemia will be measured in plasma in µg/L'}, {'measure': 'uracilemia-based DPD activity measurement', 'timeFrame': '3 years', 'description': 'differentiation between deficient and non-deficient patients will be based on uracilemia (\\<16, ≥16)'}, {'measure': 'assessment of renal function using eGFR', 'timeFrame': '3 years', 'description': 'eGFR is expressed in ml/min/1.73m²'}, {'measure': 'sex', 'timeFrame': '3 years', 'description': 'M/F used for eGFR calculation'}, {'measure': 'Age', 'timeFrame': '3 years', 'description': 'Years, used for eGFR calculation'}, {'measure': 'creatininemia', 'timeFrame': '3 years', 'description': 'µmol/l, used for eGFR calculation'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Renal Impairment', 'Digestive Cancers', 'Breast Cancer']}, 'descriptionModule': {'briefSummary': 'Fluoropyrimidine drugs (5-Fluorouracil or 5-FU and its prodrug capecitabine) are a widely used in the treatment of numerous solid tumors in adults. Approximately 85% of administered 5-FU is rapidly catabolized in the liver into inactive dihydrofluorouracil (5-FUH2) by dihydro-pyrimidine dehydrogenase (DPD), leaving only a small fraction of the initial drug for an eventual transformation into cytotoxic metabolites. Impeded DPD activity is associated to an increase of cytotoxic metabolites leading to potentially very severe toxicities.\n\nTo prevent these toxicities, a pre-therapeutic measurement of plasma uracil can help assess DPD activity. Indeed, uracil is an endogenous substrate of DPD and an increase in its plasma concentration may be associated with a decrease in DPD activity. In this case, a reduction of the fluoropyrimidine dose is suggested.\n\nHowever, the investigators observed that uracilemia increased concomitantly to the severity of renal impairment. There are two possible explanations for this observation. Either the renal impairment reduces the renal elimination of uracil from blood, or DPD activity is actually impaired. In both cases, this can explain an increase in plasma uracil concentration.\n\nHowever, the impact on fluoropyrimidine dosage is different in the two cases. If the increase in uracilemia is due to renal impairment, DPD activity remains unaffected and there is no need to reduce the fluoropyrimidine dose. If DPD activity is actually impaired, a reduction in the fluoropyrimidine dose is required. In cases of renal impairment, uracilemia may therefore not be as relevant for DPD assessment as in the absence of renal impairment.\n\nTo assess if DPD activity is actually impede during renal impairment, the DPD activity of Peripheral Blood Mononuclear Cells (PBMCs) will be assessed together with uracilemia in patients with or without renal impairment. As uracilemia decreases after dialysis, the DPD activity of Peripheral Blood Mononuclear Cells (PBMCs) will also be assessed in patient before and after dialysis. Four groups of 50 patients will be studied: patients with normal renal function with hyperuracilemia (uracilemia ≥ 16 ng/mL) or normal uracilemia (uracilemia \\< 16 ng/mL) ; and patients with renal impairment with hyperuracilemia (uracilemia ≥ 16 ng/mL) or normal uracilemia (uracilemia \\< 16 ng/mL).\n\nThe main objective of the study is to describe the distribution of DPD activity in these four populations. The secondary objectives are to determine in normorenal patients the optimal threshold for DPD activity in non-deficient patients, allowing differentiation between deficient and non-deficient patients based on uracilemia ; and to describe in patients with impaired renal function the distribution of uracilemia with respect to the threshold previously described with the aim of verifying the relevance of uracilemia as a marker of DPD activity in such patients.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'patients with breast or digestive cancer patients on dialysis patients with IR', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Signed written informed consent\n* Affiliation to the Social Security System\n* Patients with breast or digestive cancer for whom a fluoroptmidine therapy is being considered\n* OR Patients on dialysis (GFR \\< 10 ml/min/1.73 m²)\n* OR Nephrology patients with IR\n\nExclusion Criteria:\n\n* Patient with anemia \\< 8.5 g/dl\n* Patient with LDH \\> 2 x \\> ULN\n* Legal incapacity or limited legal capacity\n* Subject without health insurance\n* Subject in the exclusion period of another study or in the "national volunteer file"'}, 'identificationModule': {'nctId': 'NCT07124403', 'acronym': 'DESIR', 'briefTitle': 'DESIR. Evaluation of the Pre-therapeutic Activity of Dihydropyrimidine dEShydrogenase (DPD) in Patients With Cancer and/or Renal Failure', 'organization': {'class': 'OTHER', 'fullName': 'Centre Hospitalier Universitaire de Besancon'}, 'officialTitle': 'Evaluation of the Pre-therapeutic Activity of Dihydropyrimidine dEShydrogenase (DPD) in Patients With Cancer and/or Renal Failure', 'orgStudyIdInfo': {'id': '2024/907'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'PATIENT WITH SOLID TUMOR OR RENAL IMPAIRMENT', 'interventionNames': ['Diagnostic Test: blood sampling']}], 'interventions': [{'name': 'blood sampling', 'type': 'DIAGNOSTIC_TEST', 'description': 'DPD Activity wil be assessed from blood samples', 'armGroupLabels': ['PATIENT WITH SOLID TUMOR OR RENAL IMPAIRMENT']}, {'name': 'Blood sampling', 'type': 'DIAGNOSTIC_TEST', 'description': 'Measurement of uracilemia and assessment of renal function', 'armGroupLabels': ['PATIENT WITH SOLID TUMOR OR RENAL IMPAIRMENT']}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Centre Hospitalier Universitaire de Besancon', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}