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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Capsules, Oral, QD x 14 days until MTD is reached, 14d per 28 day cycle/QD 12 months
Dana-Farber Cancer Institute-Vendor
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
Local Institution - 003
Toronto, Ontario, Canada
Number of Participants With Dose Limiting Toxicities (DLTs) of BMS-863233
DLT is defined based on adverse events that are deemed to be drug-related and occur during the first cycle of therapy using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
Time frame: Up to 28 days
Number of Participants With Adverse Events (AEs)
Number of participants with any grade adverse events (AEs), any grade drug-related AEs, any grade serious adverse events (SAEs), any grade drug-related SAEs, and any grade AEs leading to discontinuation of any drug. The severity of AEs will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose to 30 days post last dose (Up to 14 months)
Number of Participants Who Died
Number of participants who died due to any cause.
Time frame: From first dose to 30 days post last dose (Up to 14 months)
Number of Participants With Lab Abnormalities Grade 3-4
Number of participants with lab abnormalities grade 3-4 including hematology, chemistry, coagulation, liver and kidney function, and electrolytes using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade 3 = severe Grade 4 = very severe
Time frame: From first dose to 30 days post last dose (Up to 14 months)
BMS-863233 Maximum Observed Plasma Concentration (Cmax)
BMS-863233 maximum observed plasma concentration (Cmax) is derived from plasma concentration versus time data. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
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Local Institution
Toronto, Ontario, Canada
Local Institution
Villejuif, France
Time frame: 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
BMS-863233 Time of Maximum Observed Plasma Concentration (Tmax)
BMS-863233 time of maximum observed plasma concentration (Tmax) is derived from plasma concentration versus time data.
Time frame: 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
BMS-863233 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU))
BMS-863233 Area under the concentration-time curve in one dosing interval (AUC(TAU)) is derived from plasma concentration versus time data. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
Time frame: 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
BMS-863233 Clearance (CL)
BMS-863233 clearance (CL) is derived from plasma concentration versus time data. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
Time frame: 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
BMS-863233 Effective Elimination Half-Life (T-HALFeff)
Effective elimination half-life (T-HALFeff) is derived from plasma concentration versus time data.
Time frame: 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
BMS-863233 Accumulation Index (AI_AUC)
BMS-863233 accumulation index (AI\_AUC) is derived from plasma concentration versus time data. AI is calculated based on ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
Time frame: 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
BMS-863233 Trough Observed Plasma Concentration (Ctrough)
BMS-863233 trough observed plasma concentration (Ctrough) is derived from plasma concentration versus time data. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
Time frame: 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
Change From Baseline in Electrocardiogram (ECG) Parameters: Mean Heart Rate
Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.
Time frame: Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C3D1, C4D1, C1D2, C1D15, C3D15,
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval
Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.
Time frame: Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1
Change From Baseline in Electrocardiogram (ECG) Parameters: QRS Interval
Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.
Time frame: Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1
Change From Baseline in Electrocardiogram (ECG) Parameters: QTcF Interval
Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.
Time frame: Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1
Objective Response Rate (ORR)
ORR is defined as the total percentage of participants whose best response is either a complete response (CR) or a partial response (PR) defined by the RECIST criteria. CR= Complete disappearance of all tumor lesions. PR= Decrease, relative to baseline, of 30% or greater in the sum of the longest diameter of all "target" lesions.
Time frame: From first dose up to 14 months
Disease Control Rate (DCR)
DCR is defined as the total percentage of participants whose best response is complete response (CR), partial response (PR), or ≥ 4 months stable disease (SD) defined by the RECIST criteria. CR= Complete disappearance of all tumor lesions. PR= Decrease, relative to baseline, of 30% or greater in the sum of the longest diameter of all "target" lesions. SD= Failure to meet criteria for complete or partial response, in the absence of progressive disease.
Time frame: From first dose up to 14 months