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

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Australia
    • Victoria
      • Parkville, Victoria, Australia, 3050
        • Local Institution
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Local Institution
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Local Institution
  • United States
    • California
      • Los Angeles, California, United States, 90033
        • USC/Norris Comprehensive Cancer Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A: Dose Escalation (BMS-986115)
Continuous daily dosing until disease progression or unacceptable toxicity
Drug: BMS-986115
Other Names:
  • BMS-986115 (Notch Inhibitor)
Experimental: Arm A: Dose Expansion (BMS-986115)
Continuous daily dosing until disease progression or unacceptable toxicity
Drug: BMS-986115
Other Names:
  • BMS-986115 (Notch Inhibitor)
Experimental: Arm B: Dose Escalation (BMS-986115)
Twice weekly dosing until disease progression or unacceptable toxicity
Drug: BMS-986115
Other Names:
  • BMS-986115 (Notch Inhibitor)
Experimental: Arm B: Dose Expansion (BMS-986115)
Twice weekly dosing until disease progression or unacceptable toxicity
Drug: BMS-986115
Other Names:
  • BMS-986115 (Notch Inhibitor)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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)
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
Up to 30 days after the last dose of study medication (approximately 18 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)

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
Screening (within 30 days prior to Day 1), Every 8 weeks, End of Treatment or 30-Day follow-up visits (approximately 18 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bristol-Myers Squibb

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 11, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 11, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 18, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 15, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 13, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2016

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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