A Study of BMS-863233 in Patients With Advanced and/or Metastatic Solid Tumors

Phase 1

Terminated

• Conditions: Advanced Solid Cancers; Metastatic Cancer
• Interventions: Drug: Cdc7-inhibitor

• Registration Number: NCT00886782
• Lead Sponsor: Bristol-Myers Squibb

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2009-04-22
• Study First Submitted QC: 2009-04-22
• Study First Posted: 2009-04-23
• Study Start: 2009-05-31
• Primary Completion: 2010-08-04
• Study Completion: 2010-08-04
• Disposition First Submitted: 2012-04-25
• Disposition First Submitted QC: 2015-09-23
• Disposition First Posted: 2015-10-12
• Status Verified: 2023-04
• Results First Submitted: 2023-04-04
• Results First Submitted QC: 2023-04-26
• Last Update Submitted: 2023-04-26
• Results First Posted: 2023-04-28
• Last Update Posted: 2023-04-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 11

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cdc7-inhibitor	Cdc7-inhibitor	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities (DLTs) of BMS-863233	Up to 28 days	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.
Number of Participants With Adverse Events (AEs)	From first dose to 30 days post last dose (Up to 14 months)	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.
Number of Participants Who Died	From first dose to 30 days post last dose (Up to 14 months)	Number of participants who died due to any cause.
Number of Participants With Lab Abnormalities Grade 3-4	From first dose to 30 days post last dose (Up to 14 months)	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

Secondary Outcome Measures

Name	Time	Method
BMS-863233 Maximum Observed Plasma Concentration (Cmax)	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 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.
BMS-863233 Time of Maximum Observed Plasma Concentration (Tmax)	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) is derived from plasma concentration versus time data.
BMS-863233 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU))	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)) 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.
BMS-863233 Clearance (CL)	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) 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.
BMS-863233 Effective Elimination Half-Life (T-HALFeff)	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	Effective elimination half-life (T-HALFeff) is derived from plasma concentration versus time data.
BMS-863233 Accumulation Index (AI_AUC)	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 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.
BMS-863233 Trough Observed Plasma Concentration (Ctrough)	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	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.
Change From Baseline in Electrocardiogram (ECG) Parameters: Mean Heart Rate	Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C3D1, C4D1, C1D2, C1D15, C3D15,	Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval	Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1	Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.
Change From Baseline in Electrocardiogram (ECG) Parameters: QRS Interval	Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1	Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.
Change From Baseline in Electrocardiogram (ECG) Parameters: QTcF Interval	Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1	Baseline = Last non-missing result with a collection date-time less than the date-time of the first active dose of study medication.
Objective Response Rate (ORR)	From first dose up to 14 months	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.
Disease Control Rate (DCR)	From first dose up to 14 months	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.

Trial Locations

Locations (5)

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Local Institution; 🇫🇷 Villejuif Cedex, France

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Dana-Farber Cancer Institute-Vendor; 🇺🇸 Boston, Massachusetts, United States

Local Institution - 003; 🇨🇦 Toronto, Ontario, Canada