Ignite Creation Date:
2025-12-25 @ 3:20 AM
Ignite Modification Date:
2025-12-26 @ 1:58 AM
Study NCT ID:
NCT01695005
Status:
COMPLETED
Last Update Posted:
2018-08-07
First Post:
2012-09-24
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
A Study of LY3039478 in Participants With Advanced Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'submissionInfos': [{'resetDate': '2025-07-11', 'releaseDate': '2025-06-20'}, {'resetDate': '2025-08-27', 'releaseDate': '2025-08-05'}, {'resetDate': '2025-10-02', 'releaseDate': '2025-09-22'}, {'resetDate': '2025-11-11', 'releaseDate': '2025-10-28'}, {'releaseDate': '2025-12-05'}], 'estimatedResultsFirstSubmitDate': '2025-06-20'}}, 'conditionBrowseModule': {'meshes': [{'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009362', 'term': 'Neoplasm Metastasis'}, {'id': 'D008223', 'term': 'Lymphoma'}], 'ancestors': [{'id': 'D009385', 'term': 'Neoplastic Processes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000654634', 'term': 'crenigacestat'}, {'id': 'D011241', 'term': 'Prednisone'}], 'ancestors': [{'id': 'D011244', 'term': 'Pregnadienediols'}, {'id': 'D011245', 'term': 'Pregnadienes'}, {'id': 'D011278', 'term': 'Pregnanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 237}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2012-10'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-08', 'completionDateStruct': {'date': '2018-06-26', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-08-06', 'studyFirstSubmitDate': '2012-09-24', 'studyFirstSubmitQcDate': '2012-09-24', 'lastUpdatePostDateStruct': {'date': '2018-08-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2012-09-27', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2018-06-26', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Part A and F: Number of Participants with Dose Limiting Toxicities (DLTs)', 'timeFrame': 'Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)'}, {'measure': 'Part B, C, D, E and F: Number of Participants with Tumor Response', 'timeFrame': 'Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)'}], 'secondaryOutcomes': [{'measure': 'Pharmacokinetics: Maximum Concentration (Cmax) of LY3039478', 'timeFrame': 'Predose up to 30 hours post dose'}, {'measure': 'Pharmacokinetics: Time to Maximum Concentration (Tmax) of LY3039478', 'timeFrame': 'Predose up to 30 hours post dose'}, {'measure': 'Part A: Number of Participants with Tumor Response', 'timeFrame': 'Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)'}, {'measure': 'Part B, C, D, E and F: Duration of Response (DoR)', 'timeFrame': 'Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 6 Months)'}, {'measure': 'Part B, C, D, E and F: Progression Free Survival (PFS)', 'timeFrame': 'Baseline to Objective Progression or Death from Any Cause (Estimated up to 6 Months)'}, {'measure': 'Part B, C, D, E and F: Overall Survival (OS)', 'timeFrame': 'Baseline to Date of Death from Any Cause (Estimated up to 14 Months)'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Neoplasms', 'Neoplasm Metastasis', 'Lymphoma']}, 'referencesModule': {'references': [{'pmid': '40756609', 'type': 'DERIVED', 'citation': 'Michot JM, Balogh Z, Brown JR, Ribrag V, Hollebecque A, Bahleda R, Quivoron C, Ammari S, Scoazec JY, Benhadji KA, Massard C. Notch pathway inhibition with crenigacestat (LY3039478) in a phase I first-in-human clinical trial for patients with relapsed or refractory non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia. Ther Adv Drug Saf. 2025 Jul 31;16:20420986241311461. doi: 10.1177/20420986241311461. eCollection 2025.'}, {'pmid': '32915419', 'type': 'DERIVED', 'citation': 'Azaro A, Baldini C, Rodon J, Soria JC, Yuen E, Lithio A, Oakley G, Benhadji KA, Massard C. Phase 1 study of 2 high dose intensity schedules of the pan-Notch inhibitor crenigacestat (LY3039478) in combination with prednisone in patients with advanced or metastatic cancer. Invest New Drugs. 2021 Feb;39(1):193-201. doi: 10.1007/s10637-020-00944-z. Epub 2020 Sep 11.'}, {'pmid': '30218977', 'type': 'DERIVED', 'citation': 'Mir O, Azaro A, Merchan J, Chugh R, Trent J, Rodon J, Ohnmacht U, Diener JT, Smith C, Yuen E, Oakley GJ 3rd, Le Cesne A, Soria JC, Benhadji KA, Massard C. Notch pathway inhibition with LY3039478 in soft tissue sarcoma and gastrointestinal stromal tumours. Eur J Cancer. 2018 Nov;103:88-97. doi: 10.1016/j.ejca.2018.08.012. Epub 2018 Sep 12.'}, {'pmid': '30060061', 'type': 'DERIVED', 'citation': 'Massard C, Azaro A, Soria JC, Lassen U, Le Tourneau C, Sarker D, Smith C, Ohnmacht U, Oakley G, Patel BKR, Yuen ESM, Benhadji KA, Rodon J. First-in-human study of LY3039478, an oral Notch signaling inhibitor in advanced or metastatic cancer. Ann Oncol. 2018 Sep 1;29(9):1911-1917. doi: 10.1093/annonc/mdy244.'}], 'seeAlsoLinks': [{'url': 'https://www.lillytrialguide.com/en-US/studies/solid-tumor/JJCA#?postal=', 'label': 'Click here for more information about this study: A Study of LY3039478 in Participants with Advanced Cancer'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to find a recommended dose level of LY3039478 that can safely be taken by participants with advanced cancer or cancer that has spread to other parts of the body, including but not limited to lymphoma. The study will also explore changes to various markers in blood cells and tissue. Finally, the study will help to document any tumor activity this drug may have.', 'detailedDescription': 'In Part A of this study, participants with advanced/metastatic cancer (including lymphoma) will receive increasing doses of LY3039478 to define the dose level for Part B, C, D and E. In Part B, C, D and E LY3039478 will be explored at a predefined fixed dose level. Participants in Part B and D must have a defined alteration in a certain molecular pathway. Enrollment of participants in Part B, C, D and E will start once Part A is completed. In Part F participants will receive increasing doses of LY3039478 in combination with prednisone to define the maximum tolerated dose level.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* For all parts: The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have failed to provide clinical benefit for their advanced or metastatic cancer.\n* For Dose Escalation (Part A): The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced or metastatic.\n* For Part B: All participants must have a histological evidence of their advanced or metastatic cancer and prescreened alterations in a defined pathway.\n* For Part C: All participants must have histological evidence of advanced or metastatic specific subtypes of soft tissue sarcoma.\n* For Part D: All participants must have histological evidence of advanced or metastatic cancer and prescreened alterations in a defined pathway.\n* Cohort 1: Participants must have triple negative breast cancer.\n* Cohort 2: Participants must have hepatocellular carcinoma (HCC). These participants should have Child-Pugh stage A.\n* Cohort 3: Participants must have cholangiocarcinoma.\n* Cohort 4: Participants must have chronic lymphocytic leukemia.\n* Cohort 5: Participants must have a mature T cell, B cell, or natural killer (NK) cell neoplasm.\n* For Part E: Participants must have adenoid cystic carcinoma (ACC).\n* For Part F dose confirmation: Participants must have leiomyosarcoma and prescreened alterations in a defined pathway.\n* As defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the Revised Response Criteria for Malignant Lymphoma or the Response Assessment in Neuro Oncology (RANO) criteria for glioblastoma:\n\n * For Dose Escalation (Part A): Have measurable or nonmeasurable disease.\n * For Parts B, C, D, E and F: Have measurable disease or reliable biomarker measure.\n* For Parts B, C, D, E and F: Have available tumor tissue.\n* Have adequate organ function.\n* Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale and life expectancy of more than 12 weeks.\n\nExclusion Criteria:\n\n* Have symptomatic or non stable central nervous system (CNS) malignancy.\n* Females who are pregnant or lactating.\n* Have active bacterial, fungal, and/or known viral infection.\n* Have malabsorptive syndromes, enteropathies, gastroenteritis (acute or chronic), or diarrhea (acute or chronic).\n* Participants with HCC that:\n\n * Have known HCC with fibro-lamellar or mixed histology.\n * Have presence of clinically relevant ascites.\n * Have had a liver transplant.\n * Have active or uncontrolled clinically serious hepatitis B virus or hepatitis C virus infection.'}, 'identificationModule': {'nctId': 'NCT01695005', 'briefTitle': 'A Study of LY3039478 in Participants With Advanced Cancer', 'organization': {'class': 'INDUSTRY', 'fullName': 'Eli Lilly and Company'}, 'officialTitle': 'A Phase 1 Study of LY3039478 in Patients With Advanced or Metastatic Cancer', 'orgStudyIdInfo': {'id': '14547'}, 'secondaryIdInfos': [{'id': 'I6F-MC-JJCA', 'type': 'OTHER', 'domain': 'Eli Lilly and Company'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'LY3039478 - Dose Escalation', 'description': 'Part A: LY3039478 administered orally three times per week (TIW) at escalating doses (2.5 milligrams \\[mg\\] to 100 mg) for two 28 day cycles. Participants receiving benefit may continue until disease progression', 'interventionNames': ['Drug: LY3039478']}, {'type': 'EXPERIMENTAL', 'label': 'LY3039478 - Cohort Expansion', 'description': 'Part B, C, D and E: LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression.', 'interventionNames': ['Drug: LY3039478']}, {'type': 'EXPERIMENTAL', 'label': 'Dose 1 LY3039478 + Prednisone', 'description': 'Part F1: LY3039478 administered orally TIW for 28 day cycles. Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.', 'interventionNames': ['Drug: LY3039478', 'Drug: Prednisone']}, {'type': 'EXPERIMENTAL', 'label': 'Dose 2 LY3039478 + Prednisone', 'description': 'Part F2: LY3039478 administered orally TIW (twice a week in cycle 1) for 28 day cycles. Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only. Participants receiving benefit may continue until disease progression.', 'interventionNames': ['Drug: LY3039478', 'Drug: Prednisone']}], 'interventions': [{'name': 'LY3039478', 'type': 'DRUG', 'description': 'Administered orally', 'armGroupLabels': ['Dose 1 LY3039478 + Prednisone', 'Dose 2 LY3039478 + Prednisone', 'LY3039478 - Cohort Expansion', 'LY3039478 - Dose Escalation']}, {'name': 'Prednisone', 'type': 'DRUG', 'description': 'Administered orally', 'armGroupLabels': ['Dose 1 LY3039478 + Prednisone', 'Dose 2 LY3039478 + Prednisone']}]}, 'contactsLocationsModule': {'locations': [{'zip': '33136', 'city': 'Miami', 'state': 'Florida', 'country': 'United States', 'facility': 'University of Miami School of Medicine', 'geoPoint': {'lat': 25.77427, 'lon': -80.19366}}, {'zip': '02215', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Harvard Medical School', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '48109', 'city': 'Ann Arbor', 'state': 'Michigan', 'country': 'United States', 'facility': 'University of Michigan', 'geoPoint': {'lat': 42.27756, 'lon': -83.74088}}, {'zip': '10032', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Columbia University Medical Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '10461', 'city': 'The Bronx', 'state': 'New York', 'country': 'United States', 'facility': 'Montefiore Medical Center', 'geoPoint': {'lat': 40.84985, 'lon': -73.86641}}, {'zip': '2100', 'city': 'Copenhagen', 'country': 'Denmark', 'facility': 'For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.', 'geoPoint': {'lat': 55.67594, 'lon': 12.56553}}, {'zip': '75248', 'city': 'Paris', 'country': 'France', 'facility': 'For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'zip': '94805', 'city': 'Villejuif', 'country': 'France', 'facility': 'For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.', 'geoPoint': {'lat': 48.7939, 'lon': 2.35992}}, {'zip': '72076', 'city': 'Tübingen', 'country': 'Germany', 'facility': 'For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.', 'geoPoint': {'lat': 48.52266, 'lon': 9.05222}}, {'zip': '08035', 'city': 'Barcelona', 'country': 'Spain', 'facility': 'For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'zip': 'SE1 9RT', 'city': 'London', 'country': 'United Kingdom', 'facility': 'For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'overallOfficials': [{'name': '1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Eli Lilly and Company'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Eli Lilly and Company', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}, 'annotationSection': {'annotationModule': {'unpostedAnnotation': {'unpostedEvents': [{'date': '2025-06-20', 'type': 'RELEASE'}, {'date': '2025-07-11', 'type': 'RESET'}, {'date': '2025-08-05', 'type': 'RELEASE'}, {'date': '2025-08-27', 'type': 'RESET'}, {'date': '2025-09-22', 'type': 'RELEASE'}, {'date': '2025-10-02', 'type': 'RESET'}, {'date': '2025-10-28', 'type': 'RELEASE'}, {'date': '2025-11-11', 'type': 'RESET'}], 'unpostedResponsibleParty': 'Eli Lilly and Company'}}}}