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

Metastatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00886782
• Other study ID #: CA198-002
• Secondary ID: EUDRACT Number:
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: May 31, 2009
• Est. completion date: August 4, 2010

Study information

• Verified date: April 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: August 4, 2010
• Est. primary completion date: August 4, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Cancers
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Drug:
• Cdc7-inhibitor
Capsules, Oral, QD x 14 days until MTD is reached, 14d per 28 day cycle/QD 12 months

Locations

Country	Name	City	State
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution - 003	Toronto	Ontario
France	Local Institution	Villejuif Cedex
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Dana-Farber Cancer Institute-Vendor	Boston	Massachusetts
United States	Karmanos Cancer Institute	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Exelixis

Countries where clinical trial is conducted

United States,  Canada,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 28 days
Primary	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.	From first dose to 30 days post last dose (Up to 14 months)
Primary	Number of Participants Who Died	Number of participants who died due to any cause.	From first dose to 30 days post last dose (Up to 14 months)
Primary	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	From first dose to 30 days post last dose (Up to 14 months)
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	BMS-863233 Effective Elimination Half-Life (T-HALFeff)	Effective elimination half-life (T-HALFeff) is derived from plasma concentration versus time data.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C3D1, C4D1, C1D2, C1D15, C3D15,
Secondary	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.	Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1
Secondary	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.	Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1
Secondary	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.	Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1
Secondary	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.	From first dose up to 14 months
Secondary	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.	From first dose up to 14 months

External Links

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