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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Solid Cancers, Metastatic Cancer

Intervention / Treatment
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* Drug: Cdc7-inhibitor


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cdc7-inhibitor<br> | Drug: Cdc7-inhibitor<br>* Capsules, Oral, QD x 14 days until MTD is reached, 14d per 28 day cycle/QD 12 months<br>* Other names: XL413;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced and/or Metastatic solid cancers