Ignite Creation Date:
2025-12-25 @ 12:43 AM
Ignite Modification Date:
2026-01-07 @ 1:12 AM
Study NCT ID:
NCT04466267
Status:
COMPLETED
Last Update Posted:
2020-07-10
First Post:
2020-07-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Molecular Mechanism of RAS Wild-type mCRC Resistance to Anti-EGFR-antibody
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015179', 'term': 'Colorectal Neoplasms'}], 'ancestors': [{'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': 'D012002', 'term': 'Rectal Diseases'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Tissues and peripheral blood'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'RETROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 40}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-03-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-07', 'completionDateStruct': {'date': '2020-07-04', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-07-06', 'studyFirstSubmitDate': '2020-07-06', 'studyFirstSubmitQcDate': '2020-07-06', 'lastUpdatePostDateStruct': {'date': '2020-07-10', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-07-10', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-03-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'The molecular mechanism of patients primary or secondary resistance to cetuximab', 'timeFrame': 'up to 36 months', 'description': 'Dynamic monitoring ctDNA to identify potential molecular mechanism of RAS wild-type mCRC patients primary or secondary resistance to cetuximab'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Colorectal Cancer']}, 'referencesModule': {'references': [{'pmid': '28632865', 'type': 'BACKGROUND', 'citation': "Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O'Neil BH, Atkins JN, Berry S, Polite BN, O'Reilly EM, Goldberg RM, Hochster HS, Schilsky RL, Bertagnolli MM, El-Khoueiry AB, Watson P, Benson AB 3rd, Mulkerin DL, Mayer RJ, Blanke C. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017 Jun 20;317(23):2392-2401. doi: 10.1001/jama.2017.7105."}, {'pmid': '27575024', 'type': 'BACKGROUND', 'citation': 'Stintzing S, Modest DP, Rossius L, Lerch MM, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmuller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Held S, Giessen-Jung C, Moehler M, Jagenburg A, Kirchner T, Jung A, Heinemann V; FIRE-3 investigators. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial. Lancet Oncol. 2016 Oct;17(10):1426-1434. doi: 10.1016/S1470-2045(16)30269-8. Epub 2016 Aug 27.'}, {'pmid': '27722750', 'type': 'BACKGROUND', 'citation': 'Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, Esser R, Lenz HJ, Heinemann V. Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. JAMA Oncol. 2017 Feb 1;3(2):194-201. doi: 10.1001/jamaoncol.2016.3797.'}, {'pmid': '27998963', 'type': 'BACKGROUND', 'citation': 'Batth IS, Mitra A, Manier S, Ghobrial IM, Menter D, Kopetz S, Li S. Circulating tumor markers: harmonizing the yin and yang of CTCs and ctDNA for precision medicine. Ann Oncol. 2017 Mar 1;28(3):468-477. doi: 10.1093/annonc/mdw619.'}, {'pmid': '28419195', 'type': 'BACKGROUND', 'citation': 'Vidal J, Muinelo L, Dalmases A, Jones F, Edelstein D, Iglesias M, Orrillo M, Abalo A, Rodriguez C, Brozos E, Vidal Y, Candamio S, Vazquez F, Ruiz J, Guix M, Visa L, Sikri V, Albanell J, Bellosillo B, Lopez R, Montagut C. Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients. Ann Oncol. 2017 Jun 1;28(6):1325-1332. doi: 10.1093/annonc/mdx125.'}]}, 'descriptionModule': {'briefSummary': 'Establishing the genetic map of primary and secondary resistance of Chinese wild RAS colorectal cancer received anti-EGFR treatment through tissues and peripheral blood NGS testing. Combination genetic data with clinical characteristics, prognosis and treatment data to explore the molecular mechanism of resistance of anti-EGFR-antibody.', 'detailedDescription': 'Cetuximab is a chimeric (mouse/human) monoclonal antibody, an epidermal growth factor receptor (EGFR) inhibitor. Many large clinical trials demonstrated that for RAS wild-type metastatic colorectal cancer (mCRC), especially left-sided RAS wild-type mCRC, cetuximab can prolong OS. But some of patients have primary resistance to cetuximab and for all patients received cetuximab will develop secondary resistance. Cell-free or circulating tumour DNA (ctDNA) including primary site and metastatic site genetic information, which can avoid tumor heterogeneity. The results of paired test detection of tissue and ctDNA showed there is 93% consistency in RAS testing. Therefore, dynamic monitoring ctDNA during anti-EGFR targeted treatment of RAS wild-type mCRC patients can implement prognosis of efficacy and response evaluation in real-time. Besides, it can monitor the variation features of resistance gene and find resistance gene in real-time. According the situation of gene change to find potential drug resistance mechanism and formulate individualization treatment plan.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'RAS wild-type metastatic colorectal cancer patients treatment with FOLFOX/FORFIRI + cetuximab', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Age≥18 years, ≤75 years, all gender;\n2. Histologically proven metastatic adenocarcinoma of colorectal cancer, no previous history of cancer;\n3. The clinical data of patient is intact;\n4. The data of patients after surgery is intact, and the prognosis follow-up data of patient is available.\n\nExclusion Criteria:\n\n1. Previous history of cancer；\n2. Intact clinical data or diagnosis results of histopathology is unavailable;\n3. Time of progression disease after treatment and follow-up data are unavailable;\n4. Patient received blood transfusion within 3 months;\n5. Other situation that researchers think it will impact the results of trails or violate ethics.'}, 'identificationModule': {'nctId': 'NCT04466267', 'briefTitle': 'The Molecular Mechanism of RAS Wild-type mCRC Resistance to Anti-EGFR-antibody', 'organization': {'class': 'OTHER', 'fullName': 'Sun Yat-sen University'}, 'officialTitle': 'The Molecular Mechanism of RAS Wild-type Metastatic Colorectal Cancer (mCRC) Resistance to Anti Epidermal Growth Factor Receptor (EGFR) Antibody', 'orgStudyIdInfo': {'id': 'anti-EGFR-antibody'}}, 'contactsLocationsModule': {'locations': [{'zip': '510060', 'city': 'Guanzhou', 'state': 'Guangdong', 'country': 'China', 'facility': 'Medical Oncology,Sun Yat-sen University Cancer Center', 'geoPoint': {'lat': 23.06828, 'lon': 113.37117}}], 'overallOfficials': [{'name': 'Ying Jin, MD.,PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Sun Yat-sen University'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Sun Yat-sen University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Clinical Professor', 'investigatorFullName': 'Ruihua Xu', 'investigatorAffiliation': 'Sun Yat-sen University'}}}}