Phase I Ascending Multiple-Dose Study of BMS-986115 in Subjects With Advanced Solid Tumors

NCT01986218 | Terminated Phase 1

• 1 other identifier: CA002-001
• Study Type: interventional
• Target: 36
• Locations: 3 countries
• Sites: 4

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

Conditions

Various Advanced Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  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

  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

  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

  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

  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

  29 timepoints up to Cycle 3 Day 1 (approximately 32 days)

Study Arms (4)

Arm A: Dose Escalation (BMS-986115)

EXPERIMENTAL

Continuous daily dosing until disease progression or unacceptable toxicity

Drug: BMS-986115

Arm A: Dose Expansion (BMS-986115)

EXPERIMENTAL

Continuous daily dosing until disease progression or unacceptable toxicity

Drug: BMS-986115

Arm B: Dose Escalation (BMS-986115)

EXPERIMENTAL

Twice weekly dosing until disease progression or unacceptable toxicity

Drug: BMS-986115

Arm B: Dose Expansion (BMS-986115)

EXPERIMENTAL

Twice weekly dosing until disease progression or unacceptable toxicity

Drug: BMS-986115

Interventions

BMS-986115 DRUG

Also known as: BMS-986115 (Notch Inhibitor)

Arm A: Dose Escalation (BMS-986115); Arm A: Dose Expansion (BMS-986115); Arm B: Dose Escalation (BMS-986115); Arm B: Dose Expansion (BMS-986115)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (4)

Usc/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Local Institution

Parkville, Victoria, 3050, Australia

Location

Local Institution

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Local Institution

Toronto, Ontario, M5G 2M9, Canada

Location

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Interventions

BMS-986115

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2013
• First Posted: November 18, 2013
• Study Start: November 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: September 15, 2016

Record last verified: 2016-09

Locations

AU (1); CA (2); US (1)