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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01986218




Registration number
NCT01986218
Ethics application status
Date submitted
11/11/2013
Date registered
18/11/2013
Date last updated
15/09/2016

Titles & IDs
Public title
Phase I Ascending Multiple-Dose Study of BMS-986115 in Subjects With Advanced Solid Tumors
Scientific title
Phase I Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-986115 in Subjects With Advanced Solid Tumors
Secondary ID [1] 0 0
CA002-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Various Advanced Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BMS-986115

Experimental: Arm A: Dose Escalation (BMS-986115) - Continuous daily dosing until disease progression or unacceptable toxicity

Experimental: Arm A: Dose Expansion (BMS-986115) - Continuous daily dosing until disease progression or unacceptable toxicity

Experimental: Arm B: Dose Escalation (BMS-986115) - Twice weekly dosing until disease progression or unacceptable toxicity

Experimental: Arm B: Dose Expansion (BMS-986115) - Twice weekly dosing until disease progression or unacceptable toxicity


Treatment: Drugs: BMS-986115
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability of multiple daily doses of BMS-986115
Timepoint [1] 0 0
Up to 30 days after the last dose of study medication (approximately 18 months)
Secondary outcome [1] 0 0
Maximum observed plasma concentration (Cmax) of BMS-986115 and its active metabolite BMT-100948
Timepoint [1] 0 0
29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Secondary outcome [2] 0 0
Time of maximum observed plasma concentration (Tmax) of BMS-986115 and its active metabolite BMT-100948
Timepoint [2] 0 0
29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Secondary outcome [3] 0 0
Trough observed plasma concentration (Ctrough) of BMS-986115 and its active metabolite BMT-100948
Timepoint [3] 0 0
29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Secondary outcome [6] 0 0
Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986115 and its active metabolite BMT-100948
Timepoint [6] 0 0
29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Secondary outcome [7] 0 0
Terminal plasma half-life (T-HALF) of BMS-986115 and its active metabolite BMT-100948
Timepoint [7] 0 0
29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Secondary outcome [8] 0 0
Apparent total body clearance (CLT/F) of BMS-986115
Timepoint [8] 0 0
29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Secondary outcome [9] 0 0
Apparent volume of distribution at steady-state (Vz/F) of BMS-986115
Timepoint [9] 0 0
29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Secondary outcome [10] 0 0
AUC Accumulation Index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986115
Timepoint [10] 0 0
29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Secondary outcome [11] 0 0
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
Timepoint [11] 0 0
29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
16 timepoints up to Cycle 2 Day 16 (approximately 20 days)
Secondary outcome [13] 0 0
Preliminary anti-tumor activity of BMS-986115 as measured by response evaluation criteria in solid tumors (RECIST)
Timepoint [13] 0 0
Screening (within 30 days prior to Day 1), Every 8 weeks, End of Treatment or 30-Day follow-up visits (approximately 18 months)

Eligibility
Key inclusion criteria
For more information regarding BMS clinical trial participation, please visit
www.BMSStudyConnect.com.



- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2016
Sample size
Target
Accrual to date
Final
36
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Local Institution - Parkville
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
Canada
State/province [2] 0 0
British Columbia
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT01986218
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01986218