Trial Outcomes & Findings for Study of Dasatinib (BMS-354825) in Patients With Solid Tumors (NCT NCT00339144)

Last Updated: 2010-12-15

Results Overview

MAD: highest dose level at which \>=1 DLTs were reported, MTD: dose one step lower than MAD. DLT: any of the following considered related to dasatinib during course 1:Grade 3(dose reduction by 1 dose level)/Grade 4:recurring nausea, vomiting or diarrhea; any other Grade \>=3 non-hematologic toxicity except alopecia or fatigue;any grade toxicity requiring two dose reductions or participant's discontinuation; Grade 4 neutropenia \<500 cells/mm\^3 for \>=5 consecutive days or febrile neutropenia; Grade 4 thrombocytopenia \<25,000 cells/mm\^3 or Grade 3 bleeding requiring platelet transfusion.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

From start of the treatment i.e.Day 1 to end of Cycle 1 i.e. Day 30 (4 weeks)

Results posted on

2010-12-15

Participant Flow

Participant milestones

Participant milestones
Measure	Dasatinib 100 mg Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Overall Study STARTED	9	3	4
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	9	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Dasatinib 100 mg Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Overall Study Disease progression	5	2	2
Overall Study Study drug toxicity	3	1	1
Overall Study Participant's request to discontinuation	1	0	1

Baseline Characteristics

Study of Dasatinib (BMS-354825) in Patients With Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.	Total n=16 Participants Total of all reporting groups
Age Continuous	58.0 years n=5 Participants	55.0 years n=7 Participants	47.5 years n=5 Participants	54.0 years n=4 Participants
Age, Customized < 65 years	7 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	14 participants n=4 Participants
Age, Customized >=65 years	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	11 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Eastern Cooperative Oncology group (ECOG) Performance Status (PS) 0 = Fully active	7 Units on a scale n=5 Participants	1 Units on a scale n=7 Participants	2 Units on a scale n=5 Participants	10 Units on a scale n=4 Participants
Eastern Cooperative Oncology group (ECOG) Performance Status (PS) 1 = Ambulatory and able to work	2 Units on a scale n=5 Participants	2 Units on a scale n=7 Participants	2 Units on a scale n=5 Participants	6 Units on a scale n=4 Participants
Eastern Cooperative Oncology group (ECOG) Performance Status (PS) 2 = Ambulatory but unable to work	0 Units on a scale n=5 Participants	0 Units on a scale n=7 Participants	0 Units on a scale n=5 Participants	0 Units on a scale n=4 Participants
Eastern Cooperative Oncology group (ECOG) Performance Status (PS) 3 = Capable of only limited self care	0 Units on a scale n=5 Participants	0 Units on a scale n=7 Participants	0 Units on a scale n=5 Participants	0 Units on a scale n=4 Participants
Eastern Cooperative Oncology group (ECOG) Performance Status (PS) 4 = Completely disabled	0 Units on a scale n=5 Participants	0 Units on a scale n=7 Participants	0 Units on a scale n=5 Participants	0 Units on a scale n=4 Participants

PRIMARY outcome

Timeframe: From start of the treatment i.e.Day 1 to end of Cycle 1 i.e. Day 30 (4 weeks)

Population: All treated participants who received at least one dose of the study drug and were evaluable for DLT.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=6 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=3 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Maximum Tolerated Dose (MTD) and Maximum Acceptable Dose (MAD) of Dasatinib as Determined by Number of Participants With Dose-Limiting Toxicities (DLTs) Related to Dasatinib Treatment	1 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: From start of study drug therapy up to 30 days after the last dose.

Population: All participants who received at least one dose of the study drug (safety population).

AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to an AE were recorded. Drug-related AEs: events with a relationship to the study therapy of certain; probable; possible; not likely or unrelated.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs (SAEs), Drug Related AEs and Discontinued Due to AEs Deaths	0 participants	0 participants	0 participants
Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs (SAEs), Drug Related AEs and Discontinued Due to AEs AEs	9 participants	3 participants	4 participants
Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs (SAEs), Drug Related AEs and Discontinued Due to AEs SAEs	1 participants	1 participants	1 participants
Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs (SAEs), Drug Related AEs and Discontinued Due to AEs Drug-related AEs	9 participants	3 participants	4 participants
Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs (SAEs), Drug Related AEs and Discontinued Due to AEs All AEs Leading to Discontinuation	3 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: From start of study drug therapy up to 30 days after the last dose.

Population: All participants who received at least one dose of the study drug.

Hematology abnormalities were graded per the National Cancer Institute (NCI) Common. Terminology Criteria (CTC) version 3.0 criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Absolute Neutrophil Count (ANC): Grade 3: 0.5 - \<1.0\*10\^9/L, Grade 4: \<0.5\*10\^9/L; lymphocytes: Grade 3: 0.2 - \<0.5\*10\^9/L, Grade 4: \<0.2\*10\^9/L.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Number of Participants With Grade 3 or 4 Hematology Abnormalities Low neutrophils count	1 participants	0 participants	0 participants
Number of Participants With Grade 3 or 4 Hematology Abnormalities Low lymphocyte count	0 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: From start of study drug therapy up to 30 days after the last dose.

Population: All participants who received at least one dose of the study drug.

Abnormalities were graded according to the NCI CTC, version 3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: phosphorous: Grade 3: 1.0-\<2.0 mg/dL, Grade 4: \<1.0 mg/dL; calcium: Grade 3: 6.0-\<7.0 or \>12.5-13.5 mg/dL, Grade 4: \<0.6-\>13.5 mg/dL; magnesium: Grade 3: \>3.0 - 8.0 mg/dL or \>1.23 - 3.30 mmol/L, Grade 4: \>8.0 mg/dL or \>3.30 mmol/L; albumin: Grade 3: \<2 g/dL or \<20 g/L.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities Low phosphorus	0 participants	0 participants	1 participants
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities Low calcium	0 participants	0 participants	1 participants
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities High magnesium	1 participants	0 participants	1 participants
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities Low albumin	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: From start of study drug therapy up to 30 days after the last dose.

Population: All treated participants who received at least one dose of the study drug.

Abnormalities were graded according to the NCI CTC, version 3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Most frequent hematology Grade 3 and 4 abnormalities occurring in \>=10% participants were recorded. Grade 3 and 4 criteria are as follows: lymphocyte count: Grade 3: 0.2 - \<0.5\*10\^9/L, Grade 4: \<0.2\*10\^9/L.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Most Frequent Grade 3-4 Hematology Abnormalities Occurring in >=10% Participants: Low Lymphocyte Count	0 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: From start of study drug therapy up to 30 days after the last dose.

Population: All participants who received at least one dose of the study drug (safety population).

Abnormalities were graded according to the NCI-CTC, version 3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Most frequent (\>=10%) serum laboratory abnormalities were recorded. The following definitions specify the NCI-CTC AE criteria for serum laboratory abnormalities in the data presented: magnesium: Grade 3: \>3.0 - 8.0 mg/dL or \>1.23 - 3.30 mmol/L, Grade 4: \>8.0 mg/dL or \>3.30 mmol/L.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Most Frequent Serum Chemistry Laboratory Abnormalities Occurring in >=10% Participants: High Magnesium	1 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: From screening, Day 1 in each treatment course and at the end of study

Population: All participants who received at least one dose of the study drug (safety population). Analysis for significant physical examination findings was not done.

Interim and final physical examinations were performed. The investigator used his/her clinical judgment to decide whether or not physical examination findings were clinically significant.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From screening, Day 1 , 8, 15 and 22 in the 1st treatment course, Day 8 and 22 in the second and subsequent courses and at the end of study

Population: All participants who received at least one dose of the study drug (safety population).

Vital signs measurements (including blood pressure, body temperature and pulse rate) were recorded. The investigator used his/her clinical judgment to decide whether or not abnormalities in vital signs were clinically significant.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Number of Participants With Clinically Meaningful Vital Signs	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: From screening Day -1, and at pre-dose, 1 and 4 hours (post-dose) on Days 1, 14 and 28 in first treatment course, at pre-dose, 1 and 4 hours (post-dose) during the second and fourth week in subsequent courses and at the end of study

Population: All participants who received at least one dose of the study drug (safety population).

Standard 12-lead ECG was used to record selected ECG parameters like RR interval (the time between the two R waves in ECG), PR interval (interval measured from the beginning of the P wave to the beginning of the QRS complex; QRS complex is the name for some of the deflections seen on a typical ECG)), QRS duration, QT interval (time between onset of ventricular depolarization and end of ventricular repolarization), QT interval corrected for heart rate using Bazett's (QTcB) and Fridericia's (QTcF) formulas.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, Day 1, Day 14 and Day 28

Population: All participants who received at least one dose of the study drug (safety population).

QT interval corrected for heart rate (QTcF) was assessed using triplicate 12-lead serial ECGs.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Number of Participants With Clinically Significant Change in QT Interval Corrected for Heart Rate (QTcF)	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28

Population: All treated participants with adequate pharmacokinetic (PK)profiles (PK population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively).

Cmax was obtained from the plasma concentration versus time data after oral administration of dasatinib.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Maximum Plasma Concentration (Cmax) of Dasatinib Day 28 (n= 3, 2, 2)	253.77 nanograms (ng)/ml Interval 161.59 to 383.92	103.32 nanograms (ng)/ml Interval 35.4 to 301.52	80.92 nanograms (ng)/ml Interval 27.07 to 241.87
Maximum Plasma Concentration (Cmax) of Dasatinib Day 1 (n = 9, 3, 4)	139.83 nanograms (ng)/ml Interval 42.29 to 282.18	127.1 nanograms (ng)/ml Interval 73.3 to 308.42	124.48 nanograms (ng)/ml Interval 25.41 to 314.69
Maximum Plasma Concentration (Cmax) of Dasatinib Day 14 (n = 5, 4, 2)	137.03 nanograms (ng)/ml Interval 41.63 to 270.93	166.43 nanograms (ng)/ml Interval 59.21 to 651.67	102.61 nanograms (ng)/ml Interval 23.85 to 441.45

SECONDARY outcome

Timeframe: Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Day 1

Population: All treated participants with adequate PK profiles (PK population).

AUC(INF), area under the plasma concentration-time curve from zero to the last time of the last quantifiable concentration within the dosing interval was calculated for Day 1.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Area Under the Plasma-concentration-time Curve [AUC (INF)] of Dasatinib on Day 1	537.98 ng*hours/ml Interval 203.2 to 781.73	544.36 ng*hours/ml Interval 346.36 to 962.79	595.62 ng*hours/ml Interval 269.14 to 1166.52

SECONDARY outcome

Timeframe: Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28

Population: All treated participants with adequate PK profiles (PK population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively).

Area under the plasma concentration-time curve within the dosing interval was determined. AUC(TAU), from time 0 to the time of the last measurable concentration (24 hours) was calculated for Day 1, 14, 28 respectively.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
AUC[TAU] of Dasatinib Day 1 (n = 9, 3, 4)	524.55 ng*hours/ml Interval 195.49 to 767.74	530.81 ng*hours/ml Interval 338.1 to 953.62	528.65 ng*hours/ml Interval 188.32 to 1123.34
AUC[TAU] of Dasatinib Day 14 (n = 5, 4, 2)	499.69 ng*hours/ml Interval 217.19 to 681.86	694.90 ng*hours/ml Interval 275.35 to 1798.79	716.27 ng*hours/ml Interval 234.86 to 2184.52
AUC[TAU] of Dasatinib Day 28 (n= 3, 2, 2)	738.76 ng*hours/ml Interval 497.44 to 1018.54	273.10 ng*hours/ml Interval 150.69 to 494.93	534.33 ng*hours/ml Interval 360.77 to 791.37

SECONDARY outcome

Timeframe: Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28

Tmax, time to reach maximum observed plasma concentration of dasatinib was obtained directly from the plasma concentration versus time data.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Time to Reach Maximum Observed Plasma Concentration of Dasatinib (Tmax) Day 1 (n = 9, 3, 4)	1.0 hours Interval 0.5 to 4.0	1.0 hours Interval 1.0 to 1.0	1.3 hours Interval 0.5 to 3.0
Time to Reach Maximum Observed Plasma Concentration of Dasatinib (Tmax) Day 14 (n = 5, 4, 2)	1.0 hours Interval 0.5 to 3.0	1.0 hours Interval 1.0 to 1.0	2.3 hours Interval 1.5 to 3.0
Time to Reach Maximum Observed Plasma Concentration of Dasatinib (Tmax) Day 28 (n= 3, 2, 2)	0.5 hours Interval 0.5 to 1.0	0.5 hours Interval 0.5 to 0.5	3.3 hours Interval 0.5 to 6.0

SECONDARY outcome

Timeframe: Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28

T-half of dasatinib was calculated using plasma concentration versus time data.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Terminal Elimination Half-life (T-half) of Dasatinib Day 1 (n = 9, 3, 4)	4.77 hours Standard Deviation 0.61	4.68 hours Standard Deviation 0.84	7.62 hours Standard Deviation 4.11
Terminal Elimination Half-life (T-half) of Dasatinib Day 14 (n = 5, 4, 2)	5.75 hours Standard Deviation 1.67	5.04 hours Standard Deviation 0.19	7.95 hours Standard Deviation 5.62
Terminal Elimination Half-life (T-half) of Dasatinib Day 28 (n= 3, 2, 2)	4.36 hours Standard Deviation 1.19	8.33 hours Standard Deviation 2.78	7.66 hours Standard Deviation 4.24

SECONDARY outcome

Timeframe: Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28

AI of Dasatinib was calculated as ratio of geometric mean of AUC(TAU) (area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration) on Day 14 or Day 28 on Day 1.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Accumulation Index (AI) of Dasatinib Day 14 (n = 5, 4, 2)	0.81 ratio Interval 0.33 to 1.02	1.78 ratio Interval 1.42 to 2.11	2.30 ratio Interval 1.25 to 4.25
Accumulation Index (AI) of Dasatinib Day 28 (n= 3, 2, 2)	1.12 ratio Interval 0.73 to 1.57	0.48 ratio Interval 0.45 to 0.52	1.72 ratio Interval 1.54 to 1.92

SECONDARY outcome

Timeframe: Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 14 and 28

Apparent oral clearance was obtained from the plasma concentration versus time data.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Mean Apparent Oral Clearance (CLo) of Dasatinib Day 14 (n = 5, 4, 2)	200.12 L/hour Full Range 134.3 • Interval 146.66 to 460.42	215.86 L/hour Full Range 204.7 • Interval 83.39 to 544.77	279.22 L/hour Full Range 537.4 • Interval 91.55 to 851.59
Mean Apparent Oral Clearance (CLo) of Dasatinib Day 28 (n= 3, 2, 2)	135.36 L/hour Full Range 53.3 • Interval 98.18 to 201.03	549.26 L/hour Full Range 489.6 • Interval 303.07 to 995.41	374.30 L/hour Full Range 231.3 • Interval 252.73 to 554.37

SECONDARY outcome

Timeframe: Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 14 and 28

Apparent volume of distribution after oral dosing was obtained from plasma concentration versus time data.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Mean Apparent Volume of Distribution (Vz/F) of Dasatinib Day 14 (n = 5, 4, 2)	1156.57 L Full Range 2010 • Interval 624.44 to 5283.67	1285.05 L Full Range 1967 • Interval 437.91 to 4780.03	2903.18 L Full Range 12216 • Interval 474.8 to 17751.5
Mean Apparent Volume of Distribution (Vz/F) of Dasatinib Day 28 (n= 3, 2, 2)	566.93 L Full Range 286 • Interval 425.51 to 935.66	3443.56 L Full Range 5920 • Interval 1234.38 to 9606.51	3362.08 L Full Range 6081 • Interval 1158.35 to 9758.36

SECONDARY outcome

Timeframe: Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28

Maximum plasma concentration was obtained from plasma concentration versus time data of metabolite (BMS-582691).

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Cmax of Metabolite BMS-582691 Day 1 (n = 8, 3, 3)	5.18 ng/ml Interval 1.93 to 11.93	2.89 ng/ml Interval 1.11 to 8.33	7.90 ng/ml Interval 4.83 to 11.91
Cmax of Metabolite BMS-582691 Day 14 (n = 5, 4, 2)	4.63 ng/ml Interval 1.26 to 11.13	4.61 ng/ml Interval 2.29 to 14.94	5.99 ng/ml Interval 1.51 to 23.74
Cmax of Metabolite BMS-582691 Day 28 (n= 3, 1, 2)	6.68 ng/ml Interval 4.26 to 9.35	4.66 ng/ml Interval 4.66 to 4.66	3.04 ng/ml Interval 1.17 to 7.91

SECONDARY outcome

Timeframe: Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28

AUC (0-t) was calculated using plasma concentration values of metabolite at time 0 to the time of the last measurable concentration (t).

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
AUC (0-t) of Metabolite BMS-582691 Day 1 (n = 8, 3, 3)	21.24 ng*hr/mL Interval 12.1 to 40.55	5.99 ng*hr/mL Interval 0.55 to 29.0	36.96 ng*hr/mL Interval 28.68 to 50.78
AUC (0-t) of Metabolite BMS-582691 Day 14 (n = 5, 4, 2)	15.24 ng*hr/mL Interval 2.02 to 35.05	26.05 ng*hr/mL Interval 8.92 to 84.33	37.65 ng*hr/mL Interval 9.35 to 151.7
AUC (0-t) of Metabolite BMS-582691 Day 28 (n= 3, 1, 2)	27.20 ng*hr/mL Interval 22.85 to 35.47	13.03 ng*hr/mL Interval 13.03 to 13.03	4.67 ng*hr/mL Interval 0.59 to 37.23

SECONDARY outcome

Timeframe: Blood samples were collected at 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 1, 14 and 28

Tmax of the metabolite was obtained using plasma concentration versus time data of metabolite BMS-582691.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Tmax of the Metabolite BMS-582691 Day 1 (n = 8, 3, 3)	1.5 hours Interval 1.0 to 4.0	1.5 hours Interval 1.0 to 1.5	2.0 hours Interval 1.5 to 2.0
Tmax of the Metabolite BMS-582691 Day 14 (n = 5, 4, 2)	1.0 hours Interval 1.0 to 3.0	1.8 hours Interval 1.5 to 3.0	3.0 hours Interval 3.0 to 3.0
Tmax of the Metabolite BMS-582691 Day 28 (n= 3, 1, 2)	1.5 hours Interval 1.0 to 1.5	1.0 hours Interval 1.0 to 1.0	1.8 hours Interval 1.5 to 2.0

SECONDARY outcome

Timeframe: Urine samples were collected at baseline (Day -1) and 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 hours (post dose) on Days 14 and 28.

Population: All treated participants with adequate pharmacodynamic (PD) profiles (PD population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively).

Urine NTx is a measure of bone metabolism. A decrease in the marker relative to baseline indicates a decrease in bone metabolism. Mean urine concentration of NTx biological marker was determined using enzyme linked immuno-sorbent assay (ELISA).

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Mean Urine Concentration of Urinary N-telopeptide Type 1 Collagen (NTx) Biological Marker Day -1 ( n= 9, 3, 4)	51.71 nmol*bone collagen equivalent (BCE)/mmol Standard Deviation 39.75	62.57 nmol*bone collagen equivalent (BCE)/mmol Standard Deviation 15.78	103.90 nmol*bone collagen equivalent (BCE)/mmol Standard Deviation 57.37
Mean Urine Concentration of Urinary N-telopeptide Type 1 Collagen (NTx) Biological Marker Day 14 (n= 6, 3, 4)	51.55 nmol*bone collagen equivalent (BCE)/mmol Standard Deviation 59.74	36.47 nmol*bone collagen equivalent (BCE)/mmol Standard Deviation 26.00	51.33 nmol*bone collagen equivalent (BCE)/mmol Standard Deviation 30.08
Mean Urine Concentration of Urinary N-telopeptide Type 1 Collagen (NTx) Biological Marker Day 28 (n= 3, 2, 2)	25.33 nmol*bone collagen equivalent (BCE)/mmol Standard Deviation 4.26	40.10 nmol*bone collagen equivalent (BCE)/mmol Standard Deviation 16.40	36.15 nmol*bone collagen equivalent (BCE)/mmol Standard Deviation 36.84

SECONDARY outcome

Timeframe: Urine samples were collected at baseline (Day -1) and 0 hour (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6 12 and 24 hours post dose on Days 14 and 28

Population: All treated participants with adequate PD profiles (PD population). The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively).

Urine levels of DPyr is a measure of bone resorption. A decrease in Dpyr relative to the baseline indicates decrease in bone metabolism. Mean urine concentration of Dpyr biological marker was determined using ELISA.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Mean Urine Concentration of Deoxypyridinoline (Dpyr) Biological Marker Day 14 (n= 6, 3, 4)	27.08 nanomol (nmol)/mL Standard Deviation 32.15	25.37 nanomol (nmol)/mL Standard Deviation 25.22	46.73 nanomol (nmol)/mL Standard Deviation 47.24
Mean Urine Concentration of Deoxypyridinoline (Dpyr) Biological Marker Day -1 (n = 9, 3, 4)	37.79 nanomol (nmol)/mL Standard Deviation 50.04	50.37 nanomol (nmol)/mL Standard Deviation 54.05	116.85 nanomol (nmol)/mL Standard Deviation 134.73
Mean Urine Concentration of Deoxypyridinoline (Dpyr) Biological Marker Day 28 (n= 3, 2, 2)	15.77 nanomol (nmol)/mL Standard Deviation 17.34	40.55 nanomol (nmol)/mL Standard Deviation 37.97	14.80 nanomol (nmol)/mL Standard Deviation 14.14

SECONDARY outcome

Timeframe: Serum samples were assessed at baseline (Day -1) and on Days 14 and 28

TRACP-5b is a measure of bone metabolism. A decrease in TRACP-5b relative to the baseline indicates decrease in bone metabolism. Serum TRACP-5b was quantified with enzyme-linked-immunosorbent serologic assay (ELISA).

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=16 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Mean Serum Concentration of Tartrate-resistant Acid Phosphatase Isoform 5b (TRACP-5b) Biological Marker Day 28 (n= 7)	3.40 U/L Standard Deviation 0.61	—	—
Mean Serum Concentration of Tartrate-resistant Acid Phosphatase Isoform 5b (TRACP-5b) Biological Marker Day -1 (n = 16)	5.13 U/L Standard Deviation 1.89	—	—
Mean Serum Concentration of Tartrate-resistant Acid Phosphatase Isoform 5b (TRACP-5b) Biological Marker Day 14 (n= 12)	4.13 U/L Standard Deviation 1.25	—	—

SECONDARY outcome

Timeframe: Serum samples were assessed on baseline (Day -1), and pre-dose on Days 14, 28

BAP is a measure of bone metabolism. A decrease in BAP relative to the baseline indicates decrease in bone metabolism. Serum BAP was quantified with ELISA.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=16 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Mean Serum Concentration of Bone Alkaline Phosphatase (BAP) Biological Marker Day -1 (n = 16)	29.11 U/L Standard Deviation 11.21	—	—
Mean Serum Concentration of Bone Alkaline Phosphatase (BAP) Biological Marker Day 14 (n= 13)	32.34 U/L Standard Deviation 11.92	—	—
Mean Serum Concentration of Bone Alkaline Phosphatase (BAP) Biological Marker Day 28 (n= 7)	28.20 U/L Standard Deviation 6.21	—	—

SECONDARY outcome

Timeframe: Plasma samples were collected on baseline (Day -1), 0 hour (pre-dose), 1 and 4 hours (post-dose) on Days 1, 14 and 28

Population: All treated participants with adequate pharmacodynamic profiles. Participants could not be evaluated as the test was discontinued due to difficulty in appropriate measurements.

Src and pSrc protein expression was planned to be evaluated in PBMC for establishing PK/PD relationship between Src/pSrc protein expression in PBMC and exposure of BMS-354825.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Within 4 weeks of first study drug administration, thereafter recorded every 4 or 8 weeks.

Population: All treated participants with measurable disease at baseline and received at least one dose of the study drug (efficacy population).

Tumor response was defined as the number of participants whose best response was CR or PR as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: disappearance of all target/non-target lesions; PR: \>= 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Outcome measures

Outcome measures
Measure	Dasatinib 100 mg n=9 Participants Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 Participants Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 Participants Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Number of Participants With Complete Response (CR) or Partial Response (PR) PR	0 participants	0 participants	0 participants
Number of Participants With Complete Response (CR) or Partial Response (PR) CR	0 participants	0 participants	0 participants

Adverse Events

Dasatinib 100 mg

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Dasatinib 150 mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Dasatinib 200 mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dasatinib 100 mg n=9 participants at risk Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 participants at risk Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 participants at risk Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Infections and infestations Perianal abscess	11.1% 1/9	0.00% 0/3	0.00% 0/4
Injury, poisoning and procedural complications Open fracture	0.00% 0/9	33.3% 1/3	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/9	0.00% 0/3	25.0% 1/4

Other adverse events

Other adverse events
Measure	Dasatinib 100 mg n=9 participants at risk Participants were administered an oral dose of 100 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 150 mg n=3 participants at risk Participants were administered an oral dose of 150 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level. Dose was not escalated above 200 mg daily.	Dasatinib 200 mg n=4 participants at risk Participants were administered an oral dose of 200 mg dasatinib tablet once daily for a period of 4 weeks. Initially, 3 participants were treated at one dose level. If no DLT was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. Dose was not escalated above 200 mg daily.
Blood and lymphatic system disorders Anemia	44.4% 4/9	66.7% 2/3	100.0% 4/4
Cardiac disorders Extrasystoles	0.00% 0/9	0.00% 0/3	25.0% 1/4
Cardiac disorders Supraventricular extrasystoles	0.00% 0/9	0.00% 0/3	25.0% 1/4
Eye disorders Conjunctival hemorrhage	11.1% 1/9	0.00% 0/3	0.00% 0/4
Eye disorders Visual disturbance	11.1% 1/9	0.00% 0/3	0.00% 0/4
Gastrointestinal disorders Constipation	55.6% 5/9	66.7% 2/3	50.0% 2/4
Gastrointestinal disorders Diarrhea	33.3% 3/9	66.7% 2/3	100.0% 4/4
Gastrointestinal disorders Vomiting	44.4% 4/9	66.7% 2/3	50.0% 2/4
Gastrointestinal disorders Nausea	55.6% 5/9	0.00% 0/3	50.0% 2/4
Gastrointestinal disorders Abdominal pain upper	22.2% 2/9	0.00% 0/3	25.0% 1/4
Gastrointestinal disorders Abdominal pain	11.1% 1/9	33.3% 1/3	0.00% 0/4
Gastrointestinal disorders Abdominal pain lower	22.2% 2/9	0.00% 0/3	0.00% 0/4
Gastrointestinal disorders Hemorrhoids	22.2% 2/9	0.00% 0/3	0.00% 0/4
Gastrointestinal disorders Stomatitis	11.1% 1/9	33.3% 1/3	0.00% 0/4
Gastrointestinal disorders Abdominal discomfort	11.1% 1/9	0.00% 0/3	0.00% 0/4
Gastrointestinal disorders Ascites	0.00% 0/9	0.00% 0/3	25.0% 1/4
Gastrointestinal disorders Proctalgia	11.1% 1/9	0.00% 0/3	0.00% 0/4
Gastrointestinal disorders Epigastric discomfort	11.1% 1/9	0.00% 0/3	0.00% 0/4
Gastrointestinal disorders Painful defecation	11.1% 1/9	0.00% 0/3	0.00% 0/4
General disorders Fatigue	55.6% 5/9	66.7% 2/3	100.0% 4/4
General disorders Edema	22.2% 2/9	0.00% 0/3	25.0% 1/4
General disorders Pyrexia	11.1% 1/9	33.3% 1/3	25.0% 1/4
General disorders Chest discomfort	0.00% 0/9	33.3% 1/3	0.00% 0/4
General disorders Chills	11.1% 1/9	0.00% 0/3	0.00% 0/4
General disorders Face edema	0.00% 0/9	33.3% 1/3	0.00% 0/4
General disorders Feeling abnormal	11.1% 1/9	0.00% 0/3	0.00% 0/4
General disorders Pain	0.00% 0/9	33.3% 1/3	0.00% 0/4
General disorders Peripheral coldness	11.1% 1/9	0.00% 0/3	0.00% 0/4
General disorders General physical health deterioration	0.00% 0/9	0.00% 0/3	25.0% 1/4
Immune system disorders Drug hypersensitivity	11.1% 1/9	0.00% 0/3	0.00% 0/4
Infections and infestations Nasopharyngitis	22.2% 2/9	0.00% 0/3	0.00% 0/4
Infections and infestations Infection	0.00% 0/9	0.00% 0/3	25.0% 1/4
Infections and infestations Influenza	0.00% 0/9	0.00% 0/3	25.0% 1/4
Infections and infestations Enteritis infectious	0.00% 0/9	0.00% 0/3	25.0% 1/4
Investigations Aspartate aminotransferase increased	44.4% 4/9	66.7% 2/3	50.0% 2/4
Investigations Alanine aminotransferase increased	33.3% 3/9	33.3% 1/3	25.0% 1/4
Investigations Blood calcium decreased	22.2% 2/9	33.3% 1/3	50.0% 2/4
Investigations White blood cell count decreased	44.4% 4/9	0.00% 0/3	0.00% 0/4
Investigations Activated partial thromboplastin time prolonged	22.2% 2/9	33.3% 1/3	0.00% 0/4
Investigations Blood creatine phosphokinase increased	11.1% 1/9	0.00% 0/3	50.0% 2/4
Investigations Gamma-glutamyltransferase increased	11.1% 1/9	33.3% 1/3	25.0% 1/4
Investigations Blood urine present	22.2% 2/9	0.00% 0/3	25.0% 1/4
Investigations Lymphocyte count decreased	0.00% 0/9	33.3% 1/3	50.0% 2/4
Investigations Protein urine	11.1% 1/9	0.00% 0/3	50.0% 2/4
Investigations Blood phosphorus decreased	0.00% 0/9	33.3% 1/3	50.0% 2/4
Investigations Blood albumin decreased	0.00% 0/9	0.00% 0/3	50.0% 2/4
Investigations Blood lactate dehydrogenase increased	22.2% 2/9	0.00% 0/3	0.00% 0/4
Investigations Blood magnesium increased	11.1% 1/9	0.00% 0/3	25.0% 1/4
Investigations Blood potassium increased	22.2% 2/9	0.00% 0/3	0.00% 0/4
Investigations Blood sodium decreased	22.2% 2/9	0.00% 0/3	0.00% 0/4
Investigations Electrocardiogram QT prolonged	11.1% 1/9	0.00% 0/3	25.0% 1/4
Investigations Hemoglobin decreased	22.2% 2/9	0.00% 0/3	0.00% 0/4
Investigations Neutrophil count decreased	22.2% 2/9	0.00% 0/3	0.00% 0/4
Investigations Platelet count decreased	11.1% 1/9	33.3% 1/3	0.00% 0/4
Investigations Protein total decreased	0.00% 0/9	0.00% 0/3	50.0% 2/4
Investigations Red blood cell count decreased	22.2% 2/9	0.00% 0/3	0.00% 0/4
Investigations Protein urine present	11.1% 1/9	0.00% 0/3	25.0% 1/4
Investigations Blood alkaline phosphatase increased	22.2% 2/9	0.00% 0/3	0.00% 0/4
Investigations Blood creatinine increased	11.1% 1/9	0.00% 0/3	0.00% 0/4
Investigations Hematocrit decreased	11.1% 1/9	0.00% 0/3	0.00% 0/4
Investigations Prothrombin time ratio increased	11.1% 1/9	0.00% 0/3	0.00% 0/4
Investigations Weight decreased	11.1% 1/9	0.00% 0/3	0.00% 0/4
Investigations Weight increased	11.1% 1/9	0.00% 0/3	0.00% 0/4
Investigations Platelet count increased	0.00% 0/9	0.00% 0/3	25.0% 1/4
Investigations Cell marker increased	11.1% 1/9	0.00% 0/3	0.00% 0/4
Metabolism and nutrition disorders Anorexia	66.7% 6/9	33.3% 1/3	100.0% 4/4
Musculoskeletal and connective tissue disorders Back pain	33.3% 3/9	0.00% 0/3	25.0% 1/4
Musculoskeletal and connective tissue disorders Pain in extremity	11.1% 1/9	33.3% 1/3	0.00% 0/4
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 1/9	0.00% 0/3	0.00% 0/4
Musculoskeletal and connective tissue disorders Flank pain	11.1% 1/9	0.00% 0/3	0.00% 0/4
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/9	0.00% 0/3	25.0% 1/4
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/9	33.3% 1/3	25.0% 1/4
Nervous system disorders Headache	33.3% 3/9	33.3% 1/3	50.0% 2/4
Nervous system disorders Dysgeusia	11.1% 1/9	33.3% 1/3	0.00% 0/4
Nervous system disorders Neuralgia	11.1% 1/9	0.00% 0/3	0.00% 0/4
Nervous system disorders Facial nerve disorder	11.1% 1/9	0.00% 0/3	0.00% 0/4
Psychiatric disorders Insomnia	11.1% 1/9	33.3% 1/3	25.0% 1/4
Psychiatric disorders Confusional state	0.00% 0/9	0.00% 0/3	25.0% 1/4
Renal and urinary disorders Dysuria	11.1% 1/9	0.00% 0/3	0.00% 0/4
Reproductive system and breast disorders Breast hemorrhage	0.00% 0/9	33.3% 1/3	25.0% 1/4
Reproductive system and breast disorders Gynecomastia	0.00% 0/9	0.00% 0/3	25.0% 1/4
Reproductive system and breast disorders Nipple swelling	0.00% 0/9	33.3% 1/3	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Pleural effusion	55.6% 5/9	33.3% 1/3	75.0% 3/4
Respiratory, thoracic and mediastinal disorders Dyspnea	11.1% 1/9	0.00% 0/3	100.0% 4/4
Respiratory, thoracic and mediastinal disorders Cough	22.2% 2/9	33.3% 1/3	25.0% 1/4
Respiratory, thoracic and mediastinal disorders Dyspnea exertional	11.1% 1/9	0.00% 0/3	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.00% 0/9	33.3% 1/3	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Nasal congestion	11.1% 1/9	0.00% 0/3	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	11.1% 1/9	0.00% 0/3	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Productive cough	11.1% 1/9	0.00% 0/3	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	0.00% 0/9	33.3% 1/3	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal discomfort	11.1% 1/9	0.00% 0/3	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Bronchial wall thickening	11.1% 1/9	0.00% 0/3	0.00% 0/4
Skin and subcutaneous tissue disorders Rash	22.2% 2/9	66.7% 2/3	50.0% 2/4
Skin and subcutaneous tissue disorders Eczema	11.1% 1/9	0.00% 0/3	0.00% 0/4
Skin and subcutaneous tissue disorders Erythema	0.00% 0/9	33.3% 1/3	0.00% 0/4
Skin and subcutaneous tissue disorders Hair colour changes	0.00% 0/9	0.00% 0/3	25.0% 1/4
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	0.00% 0/9	0.00% 0/3	25.0% 1/4
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/9	33.3% 1/3	0.00% 0/4
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/9	0.00% 0/3	25.0% 1/4
Vascular disorders Hypotension	0.00% 0/9	33.3% 1/3	0.00% 0/4
Vascular disorders Hot flush	0.00% 0/9	33.3% 1/3	0.00% 0/4

Additional Information

BMS Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER