Various Advanced CancerPhase 1NCT01986218
Phase I Ascending Multiple-Dose Study of BMS-986115 in Subjects With Advanced Solid Tumors
A Phase 1 study testing BMS-986115 in people with Various Advanced Cancer, run by Bristol-Myers Squibb at 4 sites in 3 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Various Advanced Cancer
- What is being tested?
- BMS-986115
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Nov 2013to Mar 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Canada2 sites
Local Institution
Toronto, Ontario, M5G 2M9
Local Institution
Vancouver, British Columbia, V5Z 4E6
United States1 site
Usc/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
About this study
Official title: 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
- Conditions
- Various Advanced Cancer
- Being tested
- BMS-986115
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-986115Drug
Also called BMS-986115 (Notch Inhibitor)
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Dose Escalation (BMS-986115) | Experimental | Continuous daily dosing until disease progression or unacceptable toxicity Receives: Drug: BMS-986115 |
| Arm A: Dose Expansion (BMS-986115) | Experimental | Continuous daily dosing until disease progression or unacceptable toxicity Receives: Drug: BMS-986115 |
| Arm B: Dose Escalation (BMS-986115) | Experimental | Twice weekly dosing until disease progression or unacceptable toxicity Receives: Drug: BMS-986115 |
| Arm B: Dose Expansion (BMS-986115) | Experimental | Twice weekly dosing until disease progression or unacceptable toxicity Receives: Drug: BMS-986115 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of multiple daily doses of BMS-986115
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
Measured: Up to 30 days after the last dose of study medication (approximately 18 months)
Secondary outcomes (13)
Maximum observed plasma concentration (Cmax) of BMS-986115 and its active metabolite BMT-100948
Measured: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Time of maximum observed plasma concentration (Tmax) of BMS-986115 and its active metabolite BMT-100948
Measured: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Trough observed plasma concentration (Ctrough) of BMS-986115 and its active metabolite BMT-100948
Measured: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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
Measured: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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
Measured: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986115 and its active metabolite BMT-100948
Measured: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Terminal plasma half-life (T-HALF) of BMS-986115 and its active metabolite BMT-100948
Measured: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Apparent total body clearance (CLT/F) of BMS-986115
Measured: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Apparent volume of distribution at steady-state (Vz/F) of BMS-986115
Measured: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
AUC Accumulation Index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986115
Measured: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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
Measured: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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
Measured: 16 timepoints up to Cycle 2 Day 16 (approximately 20 days)
Preliminary anti-tumor activity of BMS-986115 as measured by response evaluation criteria in solid tumors (RECIST)
Assessed by:
- 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)]
- 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)
- Overall Response Rate, defined as the proportion of subjects with BOR responses of CR or PR
- Disease Control Rate, defined as the proportion of subjects with BOR responses of CR, PR or SD
- Progression-Free Survival (or PFS), defined as time from first dose to either progressive disease, initiation of subsequent off-study therapy, or death
Measured: Screening (within 30 days prior to Day 1), Every 8 weeks, End of Treatment or 30-Day follow-up visits (approximately 18 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2013 (estimated)
- Study startNov 2013
- Primary completionMar 2016
- Study completionMar 2016
Why it stopped: (Non-safety reason, business objectives have changed)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Various Advanced CancerStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01986218
- Sponsor's protocol ID
- CA002-001
- Status last verified
- Sep 2016
- First submitted
- 11 Nov 2013
- Last updated
- 15 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-986115 in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01986218
- Acronym / sponsor ID
- CA002-001
- Conditions
- Various Advanced Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: (Non-safety reason, business objectives have changed)
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Nov 2013
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 18 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm A: Dose Escalation (BMS-986115) | Experimental | Drug: BMS-986115Continuous daily dosing until disease progression or unacceptable toxicity |
| Arm A: Dose Expansion (BMS-986115) | Experimental | Drug: BMS-986115Continuous daily dosing until disease progression or unacceptable toxicity |
| Arm B: Dose Escalation (BMS-986115) | Experimental | Drug: BMS-986115Twice weekly dosing until disease progression or unacceptable toxicity |
| Arm B: Dose Expansion (BMS-986115) | Experimental | Drug: BMS-986115Twice weekly dosing until disease progression or unacceptable toxicity |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BMS-986115Also: BMS-986115 (Notch Inhibitor) | Drug | Arm A: Dose Escalation (BMS-986115), Arm A: Dose Expansion (BMS-986115), Arm B: Dose Escalation (BMS-986115), Arm B: Dose Expansion (BMS-986115) |
Primary outcome
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)
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
13 secondary outcomes
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)
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)
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)
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)
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)
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)
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)
Apparent total body clearance (CLT/F) of BMS-986115
Time frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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)
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)
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)
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)
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)
Results and safety
The study was stopped early (reason given: (Non-safety reason, business objectives have changed)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BMS-986115 in people with Various Advanced Cancer, run by Bristol-Myers Squibb at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada, United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: (Non-safety reason, business objectives have changed)). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2016.