Trial Review

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
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
Stopped early
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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT01986218