- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01986218
Phase I Ascending Multiple-Dose Study of BMS-986115 in Subjects With Advanced Solid Tumors
September 13, 2016 updated by: Bristol-Myers Squibb
Phase I Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-986115 in Subjects With Advanced Solid Tumors
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
Study Overview
Study Type
Interventional
Enrollment (Actual)
36
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Victoria
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Parkville, Victoria, Australia, 3050
- Local Institution
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 4E6
- Local Institution
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Ontario
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Toronto, Ontario, Canada, M5G 2M9
- Local Institution
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California
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Los Angeles, California, United States, 90033
- USC/Norris Comprehensive Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.
Inclusion Criteria:
- 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
- Life expectancy of at least 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
- Prior anti-cancer treatments are permitted (i.e., chemotherapy, radiotherapy, hormonal, or immunotherapy)
- At least 4 weeks must have elapsed from last dose of prior anti-cancer therapy and the initiation of study therapy
Exclusion Criteria:
- Subjects with known or suspected brain metastases, primary brain tumors, or brain as the only site of disease
- Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy ≤ 7 days prior to administration of study medication
- 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
- Any major surgery or gastrointestinal disease that would interfere with administration of oral medications
- Conditions requiring chronic systemic glucocorticoid use, such as autoimmune disease or severe asthma, excluding inhalation steroids for maintenance.
- Uncontrolled or significant cardiovascular disease
- History of medically significant thromboembolic events or bleeding diathesis within the past 6 months
- Inadequate bone marrow function (Absolute neutrophil count (ANC) < 1,500 cells/mm3; Platelet count < 100,000 cells/mm3; Hemoglobin < 9.0 g/dL)
- 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
- Uncontrolled (≥ Grade 2) hypertriglyceridemia (fasting triglycerides > 300 mg/dL (3.42 mmol/L))
- Inadequate renal function (Blood creatinine > 1.5 times the institutional ULN)
- Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or Human Immunodeficiency Virus (HIV) -1, -2 antibody
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A: Dose Escalation (BMS-986115)
Continuous daily dosing until disease progression or unacceptable toxicity
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Other Names:
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Experimental: Arm A: Dose Expansion (BMS-986115)
Continuous daily dosing until disease progression or unacceptable toxicity
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Other Names:
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Experimental: Arm B: Dose Escalation (BMS-986115)
Twice weekly dosing until disease progression or unacceptable toxicity
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Other Names:
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Experimental: Arm B: Dose Expansion (BMS-986115)
Twice weekly dosing until disease progression or unacceptable toxicity
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and tolerability of multiple daily doses of BMS-986115
Time Frame: Up to 30 days after the last dose of study medication (approximately 18 months)
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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
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Up to 30 days after the last dose of study medication (approximately 18 months)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum observed plasma concentration (Cmax) of BMS-986115 and its active metabolite BMT-100948
Time Frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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Time of maximum observed plasma concentration (Tmax) of BMS-986115 and its active metabolite BMT-100948
Time Frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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Trough observed plasma concentration (Ctrough) of BMS-986115 and its active metabolite BMT-100948
Time Frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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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
Time Frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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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
Time Frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986115 and its active metabolite BMT-100948
Time Frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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Terminal plasma half-life (T-HALF) of BMS-986115 and its active metabolite BMT-100948
Time Frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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Apparent total body clearance (CLT/F) of BMS-986115
Time Frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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Apparent volume of distribution at steady-state (Vz/F) of BMS-986115
Time Frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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AUC Accumulation Index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986115
Time Frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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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
Time Frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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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
Time Frame: 16 timepoints up to Cycle 2 Day 16 (approximately 20 days)
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16 timepoints up to Cycle 2 Day 16 (approximately 20 days)
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Preliminary anti-tumor activity of BMS-986115 as measured by response evaluation criteria in solid tumors (RECIST)
Time Frame: Screening (within 30 days prior to Day 1), Every 8 weeks, End of Treatment or 30-Day follow-up visits (approximately 18 months)
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Assessed by:
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Screening (within 30 days prior to Day 1), Every 8 weeks, End of Treatment or 30-Day follow-up visits (approximately 18 months)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2013
Primary Completion (Actual)
March 1, 2016
Study Completion (Actual)
March 1, 2016
Study Registration Dates
First Submitted
November 11, 2013
First Submitted That Met QC Criteria
November 11, 2013
First Posted (Estimate)
November 18, 2013
Study Record Updates
Last Update Posted (Estimate)
September 15, 2016
Last Update Submitted That Met QC Criteria
September 13, 2016
Last Verified
September 1, 2016
More Information
Terms related to this study
Other Study ID Numbers
- CA002-001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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