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

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00886782

Enrollment

Registered

2009-04-23

Start date

2009-05-31

Completion date

2010-08-04

Last updated

2023-04-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Solid Cancers, Metastatic Cancer

Keywords

Advanced and/or Metastatic solid cancers

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.

Interventions

DRUGCdc7-inhibitor

Capsules, Oral, QD x 14 days until MTD is reached, 14d per 28 day cycle/QD 12 months

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion 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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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.
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.
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.
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.

Countries

Canada, France, United States

Participant flow

Participants by arm

Arm	Count
BMS-863233 25 mg BMS-863233 25 mg orally once daily on Days 1 to 14 of a 28-day cycle (2 weeks on treatment, 2 weeks off treatment) until progression of disease, unacceptable toxicity, withdrawal of the participant's consent, or at the discretion of the Investigator	3
BMS-863233 50 mg BMS-863233 50 mg orally once daily on Days 1 to 14 of a 28-day cycle (2 weeks on treatment, 2 weeks off treatment) until progression of disease, unacceptable toxicity, withdrawal of the participant's consent, or at the discretion of the Investigator	3
BMS-863233 100 mg BMS-863233 100 mg orally once daily on Days 1 to 14 of a 28-day cycle (2 weeks on treatment, 2 weeks off treatment) until progression of disease, unacceptable toxicity, withdrawal of the participant's consent, or at the discretion of the Investigator	5
Total	11

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse event unrelated to Study drug	0	0	1
Overall Study	Disease progression	3	3	3
Overall Study	Study drug toxicity	0	0	1

Baseline characteristics

Characteristic	BMS-863233 25 mg	BMS-863233 50 mg	BMS-863233 100 mg	Total
Age, Continuous	56.0 Years STANDARD_DEVIATION 14.73	61.0 Years STANDARD_DEVIATION 13.08	61.8 Years STANDARD_DEVIATION 7.6	60.0 Years STANDARD_DEVIATION 10.36
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants	2 Participants	3 Participants	6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants	1 Participants	2 Participants	5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	0 Participants	2 Participants
Race (NIH/OMB) White	2 Participants	2 Participants	5 Participants	9 Participants
Sex: Female, Male Female	2 Participants	1 Participants	2 Participants	5 Participants
Sex: Female, Male Male	1 Participants	2 Participants	3 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 3	1 / 3	2 / 5
other Total, other adverse events	3 / 3	2 / 3	5 / 5
serious Total, serious adverse events	1 / 3	1 / 3	4 / 5

Outcome results

Primary

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)

Population: All treated participants

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
BMS-863233 25 mg	Number of Participants Who Died	0 Participants
BMS-863233 50 mg	Number of Participants Who Died	1 Participants
BMS-863233 100 mg	Number of Participants Who Died	2 Participants

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.

Time frame: From first dose to 30 days post last dose (Up to 14 months)

Population: All treated participants

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
BMS-863233 25 mg	Number of Participants With Adverse Events (AEs)	Drug-related SAEs	0 Participants
BMS-863233 25 mg	Number of Participants With Adverse Events (AEs)	SAEs	1 Participants
BMS-863233 25 mg	Number of Participants With Adverse Events (AEs)	Drug-related AEs	1 Participants
BMS-863233 25 mg	Number of Participants With Adverse Events (AEs)	AEs leading to discontinuation	0 Participants
BMS-863233 25 mg	Number of Participants With Adverse Events (AEs)	AEs	3 Participants
BMS-863233 50 mg	Number of Participants With Adverse Events (AEs)	Drug-related AEs	0 Participants
BMS-863233 50 mg	Number of Participants With Adverse Events (AEs)	SAEs	1 Participants
BMS-863233 50 mg	Number of Participants With Adverse Events (AEs)	AEs	3 Participants
BMS-863233 50 mg	Number of Participants With Adverse Events (AEs)	Drug-related SAEs	0 Participants
BMS-863233 50 mg	Number of Participants With Adverse Events (AEs)	AEs leading to discontinuation	0 Participants
BMS-863233 100 mg	Number of Participants With Adverse Events (AEs)	SAEs	4 Participants
BMS-863233 100 mg	Number of Participants With Adverse Events (AEs)	AEs leading to discontinuation	2 Participants
BMS-863233 100 mg	Number of Participants With Adverse Events (AEs)	Drug-related SAEs	2 Participants
BMS-863233 100 mg	Number of Participants With Adverse Events (AEs)	Drug-related AEs	4 Participants
BMS-863233 100 mg	Number of Participants With Adverse Events (AEs)	AEs	5 Participants

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.

Time frame: Up to 28 days

Population: All treated participants

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
BMS-863233 25 mg	Number of Participants With Dose Limiting Toxicities (DLTs) of BMS-863233	0 Participants
BMS-863233 50 mg	Number of Participants With Dose Limiting Toxicities (DLTs) of BMS-863233	0 Participants
BMS-863233 100 mg	Number of Participants With Dose Limiting Toxicities (DLTs) of BMS-863233	1 Participants

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

Time frame: From first dose to 30 days post last dose (Up to 14 months)

Population: All treated participants

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
BMS-863233 25 mg	Number of Participants With Lab Abnormalities Grade 3-4	Hematology: Lymphocytes, low	0 Participants
BMS-863233 25 mg	Number of Participants With Lab Abnormalities Grade 3-4	Electrolytes: Hyponatremia, low	1 Participants
BMS-863233 25 mg	Number of Participants With Lab Abnormalities Grade 3-4	Liver and Kidney Function	0 Participants
BMS-863233 25 mg	Number of Participants With Lab Abnormalities Grade 3-4	Coagulation	0 Participants
BMS-863233 25 mg	Number of Participants With Lab Abnormalities Grade 3-4	Hematology: Hemoglobin, low	0 Participants
BMS-863233 25 mg	Number of Participants With Lab Abnormalities Grade 3-4	Hematology: Platelet Count, low	0 Participants
BMS-863233 25 mg	Number of Participants With Lab Abnormalities Grade 3-4	Electrolytes: Phosphorus, low	0 Participants
BMS-863233 25 mg	Number of Participants With Lab Abnormalities Grade 3-4	Other Chemistry Testing	0 Participants
BMS-863233 50 mg	Number of Participants With Lab Abnormalities Grade 3-4	Coagulation	0 Participants
BMS-863233 50 mg	Number of Participants With Lab Abnormalities Grade 3-4	Hematology: Hemoglobin, low	0 Participants
BMS-863233 50 mg	Number of Participants With Lab Abnormalities Grade 3-4	Hematology: Platelet Count, low	0 Participants
BMS-863233 50 mg	Number of Participants With Lab Abnormalities Grade 3-4	Hematology: Lymphocytes, low	0 Participants
BMS-863233 50 mg	Number of Participants With Lab Abnormalities Grade 3-4	Liver and Kidney Function	0 Participants
BMS-863233 50 mg	Number of Participants With Lab Abnormalities Grade 3-4	Electrolytes: Hyponatremia, low	0 Participants
BMS-863233 50 mg	Number of Participants With Lab Abnormalities Grade 3-4	Other Chemistry Testing	0 Participants
BMS-863233 50 mg	Number of Participants With Lab Abnormalities Grade 3-4	Electrolytes: Phosphorus, low	0 Participants
BMS-863233 100 mg	Number of Participants With Lab Abnormalities Grade 3-4	Hematology: Lymphocytes, low	1 Participants
BMS-863233 100 mg	Number of Participants With Lab Abnormalities Grade 3-4	Electrolytes: Phosphorus, low	1 Participants
BMS-863233 100 mg	Number of Participants With Lab Abnormalities Grade 3-4	Coagulation	0 Participants
BMS-863233 100 mg	Number of Participants With Lab Abnormalities Grade 3-4	Hematology: Hemoglobin, low	1 Participants
BMS-863233 100 mg	Number of Participants With Lab Abnormalities Grade 3-4	Other Chemistry Testing	0 Participants
BMS-863233 100 mg	Number of Participants With Lab Abnormalities Grade 3-4	Liver and Kidney Function	1 Participants
BMS-863233 100 mg	Number of Participants With Lab Abnormalities Grade 3-4	Hematology: Platelet Count, low	1 Participants
BMS-863233 100 mg	Number of Participants With Lab Abnormalities Grade 3-4	Electrolytes: Hyponatremia, low	1 Participants

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.

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