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

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Tumors
Intervention:	Drug: Dasatinib

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
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.

Participant Flow: Overall Study

	Dasatinib 100 mg	Dasatinib 150 mg	Dasatinib 200 mg
STARTED	9 ^[1]	3 ^[1]	4 ^[1]
COMPLETED	0	0	0
NOT COMPLETED	9	3	4
Disease progression	5	2	2
Study drug toxicity	3	1	1
Participant's request to discontinuation	1	0	1

[1]	Number of participants enrolled and treated

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
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.

Baseline Measures

	Dasatinib 100 mg	Dasatinib 150 mg	Dasatinib 200 mg	Total
Number of Participants [units: participants]	9	3	4	16
Age [units: years] Median ( Full Range )	58.0 ( 33.0 to 65.0 )	55.0 ( 39.0 to 63.0 )	47.5 ( 33.0 to 53.0 )	54.0 ( 33.0 to 65.0 )
Age, Customized [units: participants]
< 65 years	7	3	4	14
>=65 years	2	0	0	2
Gender [units: participants]
Female	7	1	3	11
Male	2	2	1	5
Eastern Cooperative Oncology group (ECOG) Performance Status (PS) ^[1] [units: Units on a scale]
0 = Fully active	7	1	2	10
1 = Ambulatory and able to work	2	2	2	6
2 = Ambulatory but unable to work	0	0	0	0
3 = Capable of only limited self care	0	0	0	0
4 = Completely disabled	0	0	0	0

[1]	The ECOG PS is used to assess disease severity. ECOG PS scores are, 0: fully active, able to carry on all pre-disease performance without restriction; 1: restricted physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2: ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3: capable of only limited self care, confined to bed or chair more than 50% of waking hours; 4: completely disabled, cannot carry on any self-care i.e. totally confined to bed or chair.

[1]

The ECOG PS is used to assess disease severity. ECOG PS scores are, 0: fully active, able to carry on all pre-disease performance without restriction; 1: restricted physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2: ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3: capable of only limited self care, confined to bed or chair more than 50% of waking hours; 4: completely disabled, cannot carry on any self-care i.e. totally confined to bed or chair.

Outcome Measures

Show All Outcome Measures

1. Primary:

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 [ Time Frame: From start of the treatment i.e.Day 1 to end of Cycle 1 i.e. Day 30 (4 weeks) ]

Show Outcome Measure 1

2. Secondary:

Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs (SAEs), Drug Related AEs and Discontinued Due to AEs [ Time Frame: From start of study drug therapy up to 30 days after the last dose. ]

Show Outcome Measure 2

3. Secondary:

Number of Participants With Grade 3 or 4 Hematology Abnormalities [ Time Frame: From start of study drug therapy up to 30 days after the last dose. ]

Show Outcome Measure 3

4. Secondary:

Number of Participants With Grade 3-4 Serum Chemistry Abnormalities [ Time Frame: From start of study drug therapy up to 30 days after the last dose. ]

Show Outcome Measure 4

5. Secondary:

Most Frequent Grade 3-4 Hematology Abnormalities Occurring in >=10% Participants: Low Lymphocyte Count [ Time Frame: From start of study drug therapy up to 30 days after the last dose. ]

Show Outcome Measure 5

6. Secondary:

Most Frequent Serum Chemistry Laboratory Abnormalities Occurring in >=10% Participants: High Magnesium [ Time Frame: From start of study drug therapy up to 30 days after the last dose. ]

Show Outcome Measure 6

7. Secondary:

Number of Participants With Clinically Meaningful Physical Examination Measures [ Time Frame: From screening, Day 1 in each treatment course and at the end of study ]

Show Outcome Measure 7

8. Secondary:

Number of Participants With Clinically Meaningful Vital Signs [ Time Frame: 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 ]

Show Outcome Measure 8

9. Secondary:

Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings [ Time Frame: 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 ]

Show Outcome Measure 9

10. Secondary:

Number of Participants With Clinically Significant Change in QT Interval Corrected for Heart Rate (QTcF) [ Time Frame: Baseline, Day 1, Day 14 and Day 28 ]

Show Outcome Measure 10

11. Secondary:

Maximum Plasma Concentration (Cmax) of Dasatinib [ Time Frame: 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 ]

Show Outcome Measure 11

12. Secondary:

Area Under the Plasma-concentration-time Curve [AUC (INF)] of Dasatinib on Day 1 [ Time Frame: 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 ]

Show Outcome Measure 12

13. Secondary:

AUC[TAU] of Dasatinib [ Time Frame: 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 ]

Show Outcome Measure 13

14. Secondary:

Time to Reach Maximum Observed Plasma Concentration of Dasatinib (Tmax) [ Time Frame: 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 ]

Show Outcome Measure 14

15. Secondary:

Terminal Elimination Half-life (T-half) of Dasatinib [ Time Frame: 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 ]

Show Outcome Measure 15

16. Secondary:

Accumulation Index (AI) of Dasatinib [ Time Frame: 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 ]

Show Outcome Measure 16

17. Secondary:

Mean Apparent Oral Clearance (CLo) of Dasatinib [ Time Frame: 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 ]

Show Outcome Measure 17

18. Secondary:

Mean Apparent Volume of Distribution (Vz/F) of Dasatinib [ Time Frame: 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 ]

Show Outcome Measure 18

19. Secondary:

Cmax of Metabolite BMS-582691 [ Time Frame: 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 ]

Show Outcome Measure 19

20. Secondary:

AUC (0-t) of Metabolite BMS-582691 [ Time Frame: 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 ]

Show Outcome Measure 20

21. Secondary:

Tmax of the Metabolite BMS-582691 [ Time Frame: 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 ]

Show Outcome Measure 21

22. Secondary:

Mean Urine Concentration of Urinary N-telopeptide Type 1 Collagen (NTx) Biological Marker [ Time Frame: 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. ]

Show Outcome Measure 22

23. Secondary:

Mean Urine Concentration of Deoxypyridinoline (Dpyr) Biological Marker [ Time Frame: 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 ]

Show Outcome Measure 23

24. Secondary:

Mean Serum Concentration of Tartrate-resistant Acid Phosphatase Isoform 5b (TRACP-5b) Biological Marker [ Time Frame: Serum samples were assessed at baseline (Day -1) and on Days 14 and 28 ]

Show Outcome Measure 24

25. Secondary:

Mean Serum Concentration of Bone Alkaline Phosphatase (BAP) Biological Marker [ Time Frame: Serum samples were assessed on baseline (Day -1), and pre-dose on Days 14, 28 ]

Show Outcome Measure 25

26. Secondary:

Number of Participants With Sarcoma (Src) and Phosphorylated Src (pSRc) Protein Expression in Peripheral Blood Mononuclear Cells (PBMC) [ Time Frame: Plasma samples were collected on baseline (Day -1), 0 hour (pre-dose), 1 and 4 hours (post-dose) on Days 1, 14 and 28 ]

Show Outcome Measure 26

27. Secondary:

Number of Participants With Complete Response (CR) or Partial Response (PR) [ Time Frame: Within 4 weeks of first study drug administration, thereafter recorded every 4 or 8 weeks. ]

Show Outcome Measure 27

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com

No publications provided

Responsible Party:	Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00339144 History of Changes
Other Study ID Numbers:	CA180-058
Study First Received:	June 19, 2006
Results First Received:	October 7, 2010
Last Updated:	November 19, 2010
Health Authority:	Japan: Ministry of Health, Labor and Welfare