Ignite Creation Date:
2025-12-25 @ 5:01 AM
Ignite Modification Date:
2026-03-15 @ 3:01 AM
Study NCT ID:
NCT01986218
Status:
TERMINATED
Last Update Posted:
2016-09-15
First Post:
2013-11-11
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase I Ascending Multiple-Dose Study of BMS-986115 in Subjects With Advanced Solid Tumors
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C000631573', 'term': 'BMS-986115'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 36}}, 'statusModule': {'whyStopped': '(Non-safety reason, business objectives have changed)', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2013-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-09', 'completionDateStruct': {'date': '2016-03', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-09-13', 'studyFirstSubmitDate': '2013-11-11', 'studyFirstSubmitQcDate': '2013-11-11', 'lastUpdatePostDateStruct': {'date': '2016-09-15', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2013-11-18', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2016-03', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Safety and tolerability of multiple daily doses of BMS-986115', 'timeFrame': 'Up to 30 days after the last dose of study medication (approximately 18 months)', 'description': 'Measured by the frequency of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, Grade 3 or 4 AEs, deaths, laboratory abnormalities and clinically relevant electrocardiogram (ECG) changes from baseline'}], 'secondaryOutcomes': [{'measure': 'Maximum observed plasma concentration (Cmax) of BMS-986115 and its active metabolite BMT-100948', 'timeFrame': '29 timepoints up to Cycle 3 Day 1 (approximately 32 days)'}, {'measure': 'Time of maximum observed plasma concentration (Tmax) of BMS-986115 and its active metabolite BMT-100948', 'timeFrame': '29 timepoints up to Cycle 3 Day 1 (approximately 32 days)'}, {'measure': 'Trough observed plasma concentration (Ctrough) of BMS-986115 and its active metabolite BMT-100948', 'timeFrame': '29 timepoints up to Cycle 3 Day 1 (approximately 32 days)'}, {'measure': 'Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of BMS-986115 and its active metabolite BMT-100948', 'timeFrame': '29 timepoints up to Cycle 3 Day 1 (approximately 32 days)'}, {'measure': 'Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986115 and its active metabolite BMT-100948', 'timeFrame': '29 timepoints up to Cycle 3 Day 1 (approximately 32 days)'}, {'measure': 'Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986115 and its active metabolite BMT-100948', 'timeFrame': '29 timepoints up to Cycle 3 Day 1 (approximately 32 days)'}, {'measure': 'Terminal plasma half-life (T-HALF) of BMS-986115 and its active metabolite BMT-100948', 'timeFrame': '29 timepoints up to Cycle 3 Day 1 (approximately 32 days)'}, {'measure': 'Apparent total body clearance (CLT/F) of BMS-986115', 'timeFrame': '29 timepoints up to Cycle 3 Day 1 (approximately 32 days)'}, {'measure': 'Apparent volume of distribution at steady-state (Vz/F) of BMS-986115', 'timeFrame': '29 timepoints up to Cycle 3 Day 1 (approximately 32 days)'}, {'measure': 'AUC Accumulation Index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986115', 'timeFrame': '29 timepoints up to Cycle 3 Day 1 (approximately 32 days)'}, {'measure': 'Ratio of metabolite AUC(INF) to parent AUC(INF) after single dose and ratio of metabolite AUC(TAU) to parent AUC(TAU) at steady state, corrected for molecular weight (MR_AUC) of BMS-986115 and its active metabolite BMT-100948', 'timeFrame': '29 timepoints up to Cycle 3 Day 1 (approximately 32 days)'}, {'measure': 'Pharmacodynamics (PD) changes in the expression of Notch pathway-related genes, including but not limited to Hes1 and Deltex1, as determined by standard molecular methods', 'timeFrame': '16 timepoints up to Cycle 2 Day 16 (approximately 20 days)'}, {'measure': 'Preliminary anti-tumor activity of BMS-986115 as measured by response evaluation criteria in solid tumors (RECIST)', 'timeFrame': 'Screening (within 30 days prior to Day 1), Every 8 weeks, End of Treatment or 30-Day follow-up visits (approximately 18 months)', 'description': "Assessed by:\n\n* Tumor Response based on the Investigator's assessment using RECIST v1.1 \\[categorized as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD)\\]\n* Best Overall Response (BOR), defined as the best tumor response recorded between the data of first dose and the last on-study tumor assessment (prior to any subsequent cancer therapy)\n* Overall Response Rate, defined as the proportion of subjects with BOR responses of CR or PR\n* Disease Control Rate, defined as the proportion of subjects with BOR responses of CR, PR or SD\n* Progression-Free Survival (or PFS), defined as time from first dose to either progressive disease, initiation of subsequent off-study therapy, or death"}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Various Advanced Cancer']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'http://www.bms.com/studyconnect/Pages/home.aspx', 'label': 'BMS clinical trial educational resource'}, {'url': 'http://www.bms.com/clinical_trials/Pages/Investigator_Inquiry_form.aspx', 'label': 'Investigator Inquiry form'}]}, 'descriptionModule': {'briefSummary': 'The primary purpose of this study is to evaluate the safety and effectiveness of daily doses of BMS-986115 in subjects with advanced solid tumors'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.\n\nInclusion Criteria:\n\n* Subjects with a histologically or cytologically confirmed diagnosis of solid tumors, advanced or metastatic, refractory to or relapsed from standard therapies or for which there is no known effective treatment\n* Life expectancy of at least 3 months\n* Eastern Cooperative Oncology Group (ECOG) performance status score 0-1\n* Prior anti-cancer treatments are permitted (i.e., chemotherapy, radiotherapy, hormonal, or immunotherapy)\n* At least 4 weeks must have elapsed from last dose of prior anti-cancer therapy and the initiation of study therapy\n\nExclusion Criteria:\n\n* Subjects with known or suspected brain metastases, primary brain tumors, or brain as the only site of disease\n* Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy ≤ 7 days prior to administration of study medication\n* Current or recent (within 3 months of study drug administration) gastrointestinal disease such as chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea, such as inflammatory bowel disease. Non-chronic conditions (e.g. infectious diarrhea) that are completely resolved for at least 2 weeks prior to starting study treatment are not exclusionary\n* Any major surgery or gastrointestinal disease that would interfere with administration of oral medications\n* Conditions requiring chronic systemic glucocorticoid use, such as autoimmune disease or severe asthma, excluding inhalation steroids for maintenance.\n* Uncontrolled or significant cardiovascular disease\n* History of medically significant thromboembolic events or bleeding diathesis within the past 6 months\n* Inadequate bone marrow function (Absolute neutrophil count (ANC) \\< 1,500 cells/mm3; Platelet count \\< 100,000 cells/mm3; Hemoglobin \\< 9.0 g/dL)\n* Inadequate hepatic function (Total bilirubin \\> 1.5 times the institutional upper limit of normal (ULN) (except known Gilbert's syndrome); Alanine transaminase (ALT) or aspartate transaminase (AST) \\> 2.5 times the institutional ULN. ALT or AST up to 3 times the institutional ULN permitted if total bilirubin is normal\n* Uncontrolled (≥ Grade 2) hypertriglyceridemia (fasting triglycerides \\> 300 mg/dL (3.42 mmol/L))\n* Inadequate renal function (Blood creatinine \\> 1.5 times the institutional ULN)\n* Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or Human Immunodeficiency Virus (HIV) -1, -2 antibody"}, 'identificationModule': {'nctId': 'NCT01986218', 'briefTitle': 'Phase I Ascending Multiple-Dose Study of BMS-986115 in Subjects With Advanced Solid Tumors', 'organization': {'class': 'INDUSTRY', 'fullName': 'Bristol-Myers Squibb'}, 'officialTitle': 'Phase I Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-986115 in Subjects With Advanced Solid Tumors', 'orgStudyIdInfo': {'id': 'CA002-001'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Arm A: Dose Escalation (BMS-986115)', 'description': 'Continuous daily dosing until disease progression or unacceptable toxicity', 'interventionNames': ['Drug: BMS-986115']}, {'type': 'EXPERIMENTAL', 'label': 'Arm A: Dose Expansion (BMS-986115)', 'description': 'Continuous daily dosing until disease progression or unacceptable toxicity', 'interventionNames': ['Drug: BMS-986115']}, {'type': 'EXPERIMENTAL', 'label': 'Arm B: Dose Escalation (BMS-986115)', 'description': 'Twice weekly dosing until disease progression or unacceptable toxicity', 'interventionNames': ['Drug: BMS-986115']}, {'type': 'EXPERIMENTAL', 'label': 'Arm B: Dose Expansion (BMS-986115)', 'description': 'Twice weekly dosing until disease progression or unacceptable toxicity', 'interventionNames': ['Drug: BMS-986115']}], 'interventions': [{'name': 'BMS-986115', 'type': 'DRUG', 'otherNames': ['BMS-986115 (Notch Inhibitor)'], 'armGroupLabels': ['Arm A: Dose Escalation (BMS-986115)', 'Arm A: Dose Expansion (BMS-986115)', 'Arm B: Dose Escalation (BMS-986115)', 'Arm B: Dose Expansion (BMS-986115)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '90033', 'city': 'Los Angeles', 'state': 'California', 'country': 'United States', 'facility': 'Usc/Norris Comprehensive Cancer Center', 'geoPoint': {'lat': 34.05223, 'lon': -118.24368}}, {'zip': '3050', 'city': 'Parkville', 'state': 'Victoria', 'country': 'Australia', 'facility': 'Local Institution', 'geoPoint': {'lat': -37.78333, 'lon': 144.95}}, {'zip': 'V5Z 4E6', 'city': 'Vancouver', 'state': 'British Columbia', 'country': 'Canada', 'facility': 'Local Institution', 'geoPoint': {'lat': 49.24966, 'lon': -123.11934}}, {'zip': 'M5G 2M9', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Local Institution', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}], 'overallOfficials': [{'name': 'Bristol-Myers Squibb', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Bristol-Myers Squibb'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Bristol-Myers Squibb', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}