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

Primary Purpose

Advanced Solid Cancers, Metastatic Cancer

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Cdc7-inhibitor
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Cancers focused on measuring Advanced and/or Metastatic solid cancers

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dana-Farber Cancer Institute-Vendor
  • Dana-Farber Cancer Institute
  • Karmanos Cancer Institute
  • Local Institution - 003
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cdc7-inhibitor

Arm Description

Outcomes

Primary Outcome Measures

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.
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.
Number of Participants Who Died
Number of participants who died due to any cause.
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

Secondary Outcome Measures

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.
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.
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.
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.
BMS-863233 Effective Elimination Half-Life (T-HALFeff)
Effective elimination half-life (T-HALFeff) is derived from plasma concentration versus time data.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
April 22, 2009
Last Updated
April 26, 2023
Sponsor
Bristol-Myers Squibb
Collaborators
Exelixis
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1. Study Identification

Unique Protocol Identification Number
NCT00886782
Brief Title
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Terminated
Study Start Date
May 31, 2009 (Actual)
Primary Completion Date
August 4, 2010 (Actual)
Study Completion Date
August 4, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
Collaborators
Exelixis

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Cancers, Metastatic Cancer
Keywords
Advanced and/or Metastatic solid cancers

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cdc7-inhibitor
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cdc7-inhibitor
Other Intervention Name(s)
BMS-863233, XL413
Intervention Description
Capsules, Oral, QD x 14 days until MTD is reached, 14d per 28 day cycle/QD 12 months
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities (DLTs) of BMS-863233
Description
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
Title
Number of Participants With Adverse Events (AEs)
Description
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)
Title
Number of Participants Who Died
Description
Number of participants who died due to any cause.
Time Frame
From first dose to 30 days post last dose (Up to 14 months)
Title
Number of Participants With Lab Abnormalities Grade 3-4
Description
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)
Secondary Outcome Measure Information:
Title
BMS-863233 Maximum Observed Plasma Concentration (Cmax)
Description
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.
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
Title
BMS-863233 Time of Maximum Observed Plasma Concentration (Tmax)
Description
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
Title
BMS-863233 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU))
Description
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
Title
BMS-863233 Clearance (CL)
Description
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
Title
BMS-863233 Effective Elimination Half-Life (T-HALFeff)
Description
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
Title
BMS-863233 Accumulation Index (AI_AUC)
Description
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
Title
BMS-863233 Trough Observed Plasma Concentration (Ctrough)
Description
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
Title
Change From Baseline in Electrocardiogram (ECG) Parameters: Mean Heart Rate
Description
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,
Title
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval
Description
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
Title
Change From Baseline in Electrocardiogram (ECG) Parameters: QRS Interval
Description
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
Title
Change From Baseline in Electrocardiogram (ECG) Parameters: QTcF Interval
Description
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
Title
Objective Response Rate (ORR)
Description
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
Title
Disease Control Rate (DCR)
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Dana-Farber Cancer Institute-Vendor
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Local Institution - 003
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Local Institution
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Local Institution
City
Villejuif Cedex
ZIP/Postal Code
94800
Country
France

12. IPD Sharing Statement

Links:
URL
http://bms.com/studyconnect/Pages/home.aspx
Description
BMS Clinical Trial Patient Recruiting

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

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