Ignite Creation Date:
2025-12-24 @ 10:56 PM
Ignite Modification Date:
2026-02-20 @ 3:44 PM
Study NCT ID:
NCT04269369
Status:
UNKNOWN
Last Update Posted:
2020-02-13
First Post:
2020-02-11
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003110', 'term': 'Colonic Neoplasms'}, {'id': 'D013274', 'term': 'Stomach Neoplasms'}, {'id': 'D001005', 'term': 'Anus Neoplasms'}, {'id': 'D010190', 'term': 'Pancreatic Neoplasms'}, {'id': 'D004938', 'term': 'Esophageal Neoplasms'}], 'ancestors': [{'id': 'D015179', 'term': 'Colorectal Neoplasms'}, {'id': 'D007414', 'term': 'Intestinal Neoplasms'}, {'id': 'D005770', 'term': 'Gastrointestinal Neoplasms'}, {'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': 'D003108', 'term': 'Colonic Diseases'}, {'id': 'D007410', 'term': 'Intestinal Diseases'}, {'id': 'D013272', 'term': 'Stomach Diseases'}, {'id': 'D012004', 'term': 'Rectal Neoplasms'}, {'id': 'D001004', 'term': 'Anus Diseases'}, {'id': 'D012002', 'term': 'Rectal Diseases'}, {'id': 'D004701', 'term': 'Endocrine Gland Neoplasms'}, {'id': 'D010182', 'term': 'Pancreatic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D006258', 'term': 'Head and Neck Neoplasms'}, {'id': 'D004935', 'term': 'Esophageal Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D005472', 'term': 'Fluorouracil'}], 'ancestors': [{'id': 'D014498', 'term': 'Uracil'}, {'id': 'D011744', 'term': 'Pyrimidinones'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'The study is not blinded (not for the patients participating in the trial and not for the treating physicians).'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'In a subgroup of patients, a parallel study model will be used. In the group of patients with genotype "wild type" and phenotype "intermediate metabolizer", a comparison will be made between group A with dosage according to French guidelines and group B with dosage according to literature. After obtaining written informed consent, patients will be randomized in a 1:1 ratio to one of the two study groups.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 250}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2020-02-18', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-02', 'completionDateStruct': {'date': '2021-09-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2020-02-12', 'studyFirstSubmitDate': '2020-02-11', 'studyFirstSubmitQcDate': '2020-02-12', 'lastUpdatePostDateStruct': {'date': '2020-02-13', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-02-13', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-09-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'The frequency of severe fluoropyrimidine-related toxicity', 'timeFrame': 'about 3 months', 'description': 'The primary endpoint of the study is the frequency of severe (National Cancer Institute Common Terminology Criteria for Adverse Events version 5 grade ≥3) fluoropyrimidine-related toxicity across the entire treatment duration. Toxicity incidence between DPYD variant allele carriers and DPYD wild-type patients and poor or intermediate metabolizers and extensive metabolizers will be compared.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Colon Cancer', 'Stomach Tumor', 'Anal Tumor', 'Pancreas Cancer', 'Esophageal Cancer']}, 'descriptionModule': {'briefSummary': 'The aim of this study is to investigate if the systematic implementation of pre-emptive geno- and phenotyping, and therefore a dose reduction based on the French guidelines and the literature during the first month of treatment, reduces grade 3 or greater toxicity in patients treated with 5-FU (5-fluorouracil) or capecitabine.\n\nTherefore, a monocentric, partial prospective and partial retrospective trail was designed.', 'detailedDescription': '5-FU (5-fluorouracil) and its oral prodrug capecitabine are commonly used drugs in various chemotherapy regimens. According to the literature, approximately 30% of the patients experience at least a grade three toxicity during treatment, mainly characterized by diarrhea, mucositis, hematological toxicity or hand-foot syndrome. This toxicity can lead to discontinuation or interruption of the therapy, hospitalization and in 1% of the cases even to mortality. This leads to an increase in health care costs, mainly driven by the cost of hospitalization.\n\nThe metabolism of 5-FU and its prodrug is primarily determined by the dehydropyrimidine dehydrogenase (DPD) enzyme. The gene encoding for this enzyme, the DPYD, is known for his genetic polymorphism. Five percent of the population has a partial DPYD deficiency and 0.01 to 0.1 percent has a full DPYP deficiency. Partial deficiency leads to a reduced activity of DPD and therefore to a reduced degradation of 5-FU or capecitabine to its inactive metabolites. This leads to an increased toxicity. The four DPYD variants considered most clinically relevant are DPYD \\* 2A, DPYD \\* 13, c.1236G\\> A and c.2846A\\> T. Patients with polymorphisms DPYD \\* 2A and DPYD \\* 13 have no residual enzyme activity, while in patients with polymorphisms 1236G\\> A and c.2846A\\> T, there is still partial enzyme activity present. In addition to genotyping, partial DPYD deficiency can also be detected by phenotyping. In the case of reduced enzyme activity of DPYD, the degradation of uracil is disturbed, causing an increase in uracil and a decrease in UH2 in plasma. There is a strong correlation between the UH2 / U ratio in plasma and the halflife, clearance and plasma levels of 5-FU.\n\nFrench guidelines, HAS (La Haute Autorité de santé), recommend to adjust the dose of these drugs at the start of treatment based on the results of both the genetic and phenotypic studies.\n\nThe aim of this study is to investigate if the systematic implementation of pre-emptive geno- and phenotyping, and therefore a dose reduction based on the French guidelines and the literature during the first month of treatment, reduces grade 3 or greater toxicity in patients treated with 5-FU or capecitabine.\n\nTherefore, a monocentric, partial prospective and partial retrospective trail was designed.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients aged 18 years or older\n* WHO (world health organization) classification 0,1 or 2\n* A suspected start with 5-FU or capecitabine in mono or combination therapy\n* The knowledge of the result of the geno and phenotyping before the start of the treatment\n\nExclusion Criteria:\n\n* Not meeting inclusion criteria\n* Homozygote genotype or uracil 100 ng/ml or greater\n* The lacking of the result of the geno and / or phenotyping before the start of treatment\n* Patients who received 5-FU or capecitabine in the past'}, 'identificationModule': {'nctId': 'NCT04269369', 'briefTitle': 'Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients', 'organization': {'class': 'OTHER', 'fullName': 'Jessa Hospital'}, 'officialTitle': 'Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients With the Aim of Reducing Toxicity', 'orgStudyIdInfo': {'id': 'FluorouracilCapecitabine001'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Group A', 'description': 'Dosage according to French guidelines', 'interventionNames': ['Drug: 5-Fluorouracil']}, {'type': 'EXPERIMENTAL', 'label': 'Group B', 'description': 'Dosage according to literature', 'interventionNames': ['Drug: 5-Fluorouracil']}], 'interventions': [{'name': '5-Fluorouracil', 'type': 'DRUG', 'description': 'The aim of this study is to investigate if the systematic implementation of pre-emptive geno- and phenotyping, and therefore a dose reduction based on the French guidelines and the literature during the first month of treatment, reduces grade 3 or greater toxicity in patients treated with 5-FU or capecitabine. Therefore a dosing table was obtained by combining the results of the study by Henricks et al., Launay et al. and Yang et al. and the recommendations from the French HAS guideline. The treatment schedule then will be discussed by the team of doctors and paramedics at the weekly MOC (multidisciplinary cancer consultation). Complementary, the pharmacist provides dose advice with regard to the start of 5-FU or capecitabine treatment.\n\nIn a subgroup, the group of patients with genotype "wild type" and phenotype "intermediate metabolizer", a comparison will be made between group A with dosage according to French guidelines and group B with dosage according to literature.', 'armGroupLabels': ['Group A', 'Group B']}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'An Lambaerts', 'role': 'CONTACT', 'email': 'an.lambaerts@jessazh.be', 'phone': '+3211338461'}, {'name': 'Liesbeth Decoutere', 'role': 'CONTACT', 'email': 'liesbeth.decoutere@jessazh.be', 'phone': '+3211338411'}], 'overallOfficials': [{'name': 'An Lambaerts', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Jessa Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Jessa Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}