Clinical trial NCT00886782: A Study of BMS-863233 in Patients With Advanced and/or Metastatic Solid Tumors
Official title: A Phase 1/2 Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-863233 in Subjects With Advanced and/or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Cancers
Metastatic Cancer
Keywords: Advanced and/or Metastatic solid cancers
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Exelixis
First posted: 2009-04-23
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine safety, tolerability and maximum tolerated dose of BMS-863233 in subjects advanced and/or Metastatic solid tumors.


Eligibility criteria: Phase 1 Inclusion Criteria:

* Subjects with advanced and/or metastatic solid tumors who are either refractory to or have relapsed from standard therapies, or for whom a standard therapy does not exist.
* ECOG performance status ≤ 2
* Accessible for treatment, PK sample collection and required study follow-up
* Total Bilirubin ≤ 1.5 x ULN and ALT, AST ≤ 2.5 x ULN

Exclusion Criteria:

* Women who are pregnant or breastfeeding
* Subjects with known or suspected brain metastasis, primary brain tumors, or brain as the only site of disease
* Exposure to any investigational agent within 4 weeks of study drug administration
* Subjects a history of gastrointestinal disease

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) of BMS-863233
timeFrame: Up to 28 days
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose to 30 days post last dose (Up to 14 months)
measure: Number of Participants Who Died
timeFrame: From first dose to 30 days post last dose (Up to 14 months)
measure: Number of Participants With Lab Abnormalities Grade 3-4
timeFrame: From first dose to 30 days post last dose (Up to 14 months)
Secondary outcomes:
measure: BMS-863233 Maximum Observed Plasma Concentration (Cmax)
timeFrame: PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-hours end-of-infusion on Cycle 1 Day 1, Cycle 1 Day 14
measure: BMS-863233 Time of Maximum Observed Plasma Concentration (Tmax)
timeFrame: PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-hours end-of-infusion on Cycle 1 Day 1, Cycle 1 Day 14
measure: BMS-863233 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU))
timeFrame: PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-hours end-of-infusion on Cycle 1 Day 1, Cycle 1 Day 14
measure: BMS-863233 Clearance (CL)
timeFrame: PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-hours end-of-infusion on Cycle 1 Day 1, Cycle 1 Day 14
measure: BMS-863233 Effective Elimination Half-Life (T-HALFeff)
timeFrame: PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-, 36-hours end-of-infusion on Cycle 1 Day 1, Cycle 1 Day 14
measure: BMS-863233 Accumulation Index (AI_AUC)
timeFrame: PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-hours end-of-infusion on Cycle 1 Day 1, Cycle 1 Day 14
measure: BMS-863233 Trough Observed Plasma Concentration (Ctrough)
timeFrame: PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-, 24-hours end-of-infusion on Cycle 1 Day 2 (C1D2), (C1D7, or D8, or D9), and C1D14
measure: Change From Baseline in Electrocardiogram (ECG) Parameters: Mean Heart Rate
timeFrame: Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C3D1, C4D1, C1D2, C1D15, C3D15,
measure: Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval
timeFrame: Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1
measure: Change From Baseline in Electrocardiogram (ECG) Parameters: QRS Interval
timeFrame: Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1
measure: Change From Baseline in Electrocardiogram (ECG) Parameters: QTcF Interval
timeFrame: Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1
measure: Objective Response Rate (ORR)
timeFrame: From first dose up to 14 months
measure: Disease Control Rate (DCR)
timeFrame: From first dose up to 14 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute-Vendor
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Toronto
country: Canada
facility: Local Institution - 003
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Villejuif Cedex
country: France
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: