Clinical trial NCT01986218: Phase I Ascending Multiple-Dose Study of BMS-986115 in Subjects With Advanced Solid Tumors
Official title: Phase I Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-986115 in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Various Advanced Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2013-11-18
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
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)
Secondary outcomes:
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)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc/Norris Comprehensive Cancer Center
state: California
city: Parkville
country: Australia
facility: Local Institution
state: Victoria
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: