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

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

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 Overview

• Status: Terminated
• Conditions: Metastatic Cancer; Advanced Solid Cancers
• Intervention / Treatment: Drug: Cdc7-inhibitor

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 003
• France
  • Villejuif Cedex, France, 94800
    • Local Institution
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute-Vendor
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cdc7-inhibitor	Drug: Cdc7-inhibitor; Capsules, Oral, QD x 14 days until MTD is reached, 14d per 28 day cycle/QD 12 months; Other Names: BMS-863233; XL413

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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)
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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,
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Exelixis

Publications and helpful links

Helpful Links

• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2009
• Primary Completion (Actual): August 4, 2010
• Study Completion (Actual): August 4, 2010

Study Registration Dates

• First Submitted: April 22, 2009
• First Submitted That Met QC Criteria: April 22, 2009
• First Posted (Estimate): April 23, 2009

Study Record Updates

• Last Update Posted (Actual): April 28, 2023
• Last Update Submitted That Met QC Criteria: April 26, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Advanced and/or Metastatic solid cancers
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: CA198-002; EUDRACT Number: 2009-010572-20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No