Ignite Creation Date:
2025-12-25 @ 2:53 AM
Ignite Modification Date:
2026-03-01 @ 5:17 PM
Study NCT ID:
NCT02278133
Status:
COMPLETED
Last Update Posted:
2017-10-09
First Post:
2014-10-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study of WNT974 in Combination With LGX818 and Cetuximab in Patients With BRAF-mutant Metastatic Colorectal Cancer (mCRC) and Wnt Pathway Mutations
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015179', 'term': 'Colorectal Neoplasms'}, {'id': 'D009362', 'term': 'Neoplasm Metastasis'}], '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'}, {'id': 'D009385', 'term': 'Neoplastic Processes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C586458', 'term': 'LGK974'}, {'id': 'C000601108', 'term': 'encorafenib'}, {'id': 'D000068818', 'term': 'Cetuximab'}], 'ancestors': [{'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 20}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-12'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-10', 'dispFirstSubmitDate': '2017-07-17', 'completionDateStruct': {'date': '2017-06-23', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-10-03', 'studyFirstSubmitDate': '2014-10-06', 'dispFirstSubmitQcDate': '2017-07-17', 'studyFirstSubmitQcDate': '2014-10-27', 'dispFirstPostDateStruct': {'date': '2017-07-18', 'type': 'ACTUAL'}, 'lastUpdatePostDateStruct': {'date': '2017-10-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2014-10-29', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2016-05-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of Dose Limiting Toxicities and exposure (AUC C1D15) to WNT974 and LGX818 (phase lb)', 'timeFrame': '12 months', 'description': 'Phase Ib: To estimate the MTD(s) and/or RP2D(s) of the triple combination of WNT974, LGX818 and cetuximab in patients with BRAFV600-mutant, KRAS wild-type (WT) mCRC harboring upstream Wnt pathway mutations.'}, {'measure': 'Overall response rate in phase II', 'timeFrame': '30 months', 'description': 'Phase II: To estimate the preliminary anti-tumor activity of the RP2D(s) of the combination of WNT974, LGX818 and cetuximab in patients with BRAFV600-mutant metastatic CRC harboring upstream Wnt pathway mutations'}], 'secondaryOutcomes': [{'measure': 'Overall response rate (ORR) (phase lb)', 'timeFrame': '36 months', 'description': 'To assess additional parameters of clinical activity of WNT974 in combination with LGX818 and cetuximab in BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation.'}, {'measure': 'Overall survival (OS) (phase lb/ll)', 'timeFrame': '36 months', 'description': 'To assess additional parameters of clinical activity of WNT974 in combination with LGX818 and cetuximab in BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation.'}, {'measure': 'Duration of response (DOR) (phase lb/ll)', 'timeFrame': '36 months', 'description': 'To assess additional parameters of clinical activity of WNT974 in combination with LGX818 and cetuximab in BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation.'}, {'measure': 'Time to response (TTR) (phase lb/ll)', 'timeFrame': '36 months', 'description': 'To assess additional parameters of clinical activity of WNT974 in combination with LGX818 and cetuximab in BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation.'}, {'measure': 'Progression free survival (PFS) (phase lb/ll)', 'timeFrame': '36 months', 'description': 'To assess additional parameters of clinical activity of WNT974 in combination with LGX818 and cetuximab in BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation.'}, {'measure': 'Disease control rate (DCR) (phase lb/ll)', 'timeFrame': '36 months', 'description': 'To assess additional parameters of clinical activity of WNT974 in combination with LGX818 and cetuximab in BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation.'}, {'measure': 'Plasma concentration of WNT974, LHA333, LGX818 (phase lb/ll)', 'timeFrame': '30 months', 'description': 'To characterize the pharmacokinetics (PK) of WNT974, its pharmacologically active metabolite LHA333, and LGX818 when used in combination therapy with cetuximab'}, {'measure': 'Number of participants with Adverse Events as a measure of safety and tolerability (phase lb/ll)', 'timeFrame': '30 months', 'description': 'To characterize the safety and tolerability of WNT974 in combination with LGX818 and cetuximab in patients with BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation'}, {'measure': 'Number of participants with Serious Adverse Events as a measure of safety and tolerability(phase lb/ll)', 'timeFrame': '30 months', 'description': 'To characterize the safety and tolerability of WNT974 in combination with LGX818 and cetuximab in patients with BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation'}, {'measure': 'Biomarker activations for WNT and RTK-MAPK pathways (phase Ib/II)', 'timeFrame': '32 months', 'description': 'Phase Ib/II: To assess the pharmacodynamic effect of WNT974, LGX818 in combination with cetuximab and a potential relationship with clinical outcome'}, {'measure': 'Number of participants with dose interruptions and dose reductions (phase Ib/II)', 'timeFrame': '30 months', 'description': 'To characterize the safety and tolerability of WNT974 in combination with LGX818 and cetuximab in patients with BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['metastatic,', 'Colorectal cancer,', 'WNT974,', 'LGX818,', 'cetuximab,', 'BRAF-mutant,', 'mCRC,', 'BRAFV600-mutant,', 'KRAS'], 'conditions': ['Metastatic Colorectal Cancer']}, 'referencesModule': {'references': [{'pmid': '40578933', 'type': 'DERIVED', 'citation': 'VAN Bussel MTJ, Bravenboer N, Essen HV, Snaebjornsson P, Appelman-Dijkstra NM, Schellens JH, Opdam FL. Bone Toxicity Case Report Combining Encorafenib, Cetuximab and WNT974 in a Phase I Trial. Anticancer Res. 2025 Jul;45(7):3137-3147. doi: 10.21873/anticanres.17677.'}, {'pmid': '36811382', 'type': 'DERIVED', 'citation': 'Tabernero J, Van Cutsem E, Garralda E, Tai D, De Braud F, Geva R, van Bussel MTJ, Fiorella Dotti K, Elez E, de Miguel MJ, Litwiler K, Murphy D, Edwards M, Morris VK. A Phase Ib/II Study of WNT974 + Encorafenib + Cetuximab in Patients With BRAF V600E-Mutant KRAS Wild-Type Metastatic Colorectal Cancer. Oncologist. 2023 Mar 17;28(3):230-238. doi: 10.1093/oncolo/oyad007.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to assess the safety and anti-tumor activity of the triple combination of WNT974, LGX818 and cetuximab in BRAFV600-mutant mCRC with RNF43 mutations or RSPO fusions.\n\nThe design of this study is based upon the translational and pre-clinical data that suggest that Wnt pathway signals, increased due to RNF43 mutations or RSPO fusions, cooperate with the EGFR and BRAF signals to maintain the growth of BRAFV600 CRCs. Inhibition of these signals with the triple combination of WNT974, LGX818 and cetuximab may result in anti-tumor activity.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Male or female aged ≥ 18 years\n* Histological or cytological confirmed metastatic colorectal cancer\n* Written documentation of KRAS wild-type status and BRAFV600-mutation with RNF43 mutation and/or RSPO fusion\n* Progression of disease after at least one prior standard of care regimen or intolerant to irinotecan based regimens\n* Availability of a representative tumor specimen (primary or metastatic, archival or newly obtained)\n* Measurable disease as per RECIST v1.1\n* Eastern cooperative oncology group (ECOG) performance status ≤ 2\n\nExclusion Criteria:\n\n* Phase II only: Prior treatment with RAF inhibitors, Wnt pathway inhibitors, cetuximab, panitumumab, and/or other EGFR inhibitors\n* Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed to enroll\n* Current treatment with medications or consuming foods that are strong inhibitors or inducers of CYP3A4/5 or herbal medications and that cannot be discontinued at least one week prior to the start of treatment.\n* Symptomatic or untreated leptomeningeal disease\n* Acute or chronic pancreatitis\n* Clinically significant cardiac disease\n* Patients with any of the following laboratory values at Screening/baseline\n\n * Absolute neutrophil count (ANC) \\<1,500/mm3\n * Platelets \\< 100,000/mm3\n * Hemoglobin \\< 9.0 g/dL\n * Serum creatinine \\>1.5 x ULN or calculated or directly measured CrCl \\< 50% lower limit of normal\n * Serum total bilirubin \\>1.5 x ULN\n * AST/SGOT and/or ALT/SGPT \\> 2.5 x ULN, (\\> 5 x ULN if liver metastases present)\n* Patients with impaired hepatic function as defined by Childs-Pugh class B or C\n* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral WNT974/LGX818\n\nOther protocol-defined inclusion/exclusion criteria may apply'}, 'identificationModule': {'nctId': 'NCT02278133', 'briefTitle': 'Study of WNT974 in Combination With LGX818 and Cetuximab in Patients With BRAF-mutant Metastatic Colorectal Cancer (mCRC) and Wnt Pathway Mutations', 'organization': {'class': 'INDUSTRY', 'fullName': 'Array BioPharma'}, 'officialTitle': 'A Phase Ib/II Multi-center, Open Label, Dose Escalation Study of WNT974, LGX818 and Cetuximab in Patients With BRAFV600-mutant KRAS Wild-type Metastatic Colorectal Cancer Harboring Wnt Pathway Mutations', 'orgStudyIdInfo': {'id': 'CWNT974X2102C'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'WNT974, LGX818 and cetuximab combo', 'description': 'Phase l: Dose Escalation phase; Phase ll: SIngle group assessing the triple combination of WNT974, LGX818 and cetuximab', 'interventionNames': ['Drug: WNT974', 'Drug: LGX818', 'Biological: Cetuximab']}], 'interventions': [{'name': 'WNT974', 'type': 'DRUG', 'armGroupLabels': ['WNT974, LGX818 and cetuximab combo']}, {'name': 'LGX818', 'type': 'DRUG', 'armGroupLabels': ['WNT974, LGX818 and cetuximab combo']}, {'name': 'Cetuximab', 'type': 'BIOLOGICAL', 'armGroupLabels': ['WNT974, LGX818 and cetuximab combo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '10065', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Memorial Sloan-Kettering Cancer Center (MSKCC) MSKCC (3)', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '29425', 'city': 'Charleston', 'state': 'South Carolina', 'country': 'United States', 'facility': 'Medical University of South Carolina Oncology Dept', 'geoPoint': {'lat': 32.77632, 'lon': -79.93275}}, {'zip': '77030-4009', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'University of Texas/MD Anderson Cancer Center Onc. Dept,', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '53792-6164', 'city': 'Madison', 'state': 'Wisconsin', 'country': 'United States', 'facility': 'University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc', 'geoPoint': {'lat': 43.07305, 'lon': -89.40123}}, {'zip': '3050', 'city': 'Parkville', 'state': 'Victoria', 'country': 'Australia', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': -37.78333, 'lon': 144.95}}, {'zip': '3000', 'city': 'Leuven', 'country': 'Belgium', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 50.87959, 'lon': 4.70093}}, {'zip': 'T6G 1Z2', 'city': 'Edmonton', 'state': 'Alberta', 'country': 'Canada', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 53.55014, 'lon': -113.46871}}, {'zip': 'V5Z 4E6', 'city': 'Vancouver', 'state': 'British Columbia', 'country': 'Canada', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 49.24966, 'lon': -123.11934}}, {'zip': 'M5G 2M9', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'zip': '33076', 'city': 'Bordeaux', 'country': 'France', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 44.84124, 'lon': -0.58046}}, {'zip': '13273', 'city': 'Marseille', 'country': 'France', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 43.29695, 'lon': 5.38107}}, {'zip': '6423906', 'city': 'Tel Aviv', 'country': 'Israel', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 32.08088, 'lon': 34.78057}}, {'zip': '20133', 'city': 'Milan', 'state': 'MI', 'country': 'Italy', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 42.78235, 'lon': 12.59836}}, {'zip': '1066 CX', 'city': 'Amsterdam', 'country': 'Netherlands', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 52.37403, 'lon': 4.88969}}, {'zip': '169610', 'city': 'Singapore', 'country': 'Singapore', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 1.28967, 'lon': 103.85007}}, {'zip': '08035', 'city': 'Barcelona', 'state': 'Catalonia', 'country': 'Spain', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'zip': '08907', 'city': "L'Hospitalet de Llobregat", 'state': 'Catalonia', 'country': 'Spain', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 41.35967, 'lon': 2.10028}}, {'zip': '28041', 'city': 'Madrid', 'country': 'Spain', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 40.4165, 'lon': -3.70256}}, {'zip': '28050', 'city': 'Madrid', 'country': 'Spain', 'facility': 'Array BioPharma Investigative Site', 'geoPoint': {'lat': 40.4165, 'lon': -3.70256}}], 'overallOfficials': [{'name': 'Clinical Trial Call Center', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Array BioPharma, Inc.'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Array BioPharma', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}