Phase 1
N=16
Study of Dasatinib (BMS-354825) in Patients With Solid Tumors
Tumors
Bottom Line
View on ClinicalTrials.gov: NCT00339144 ↗Enrolled (actual)
16
Serious AEs
18.8%
Results posted
Dec 2010
Primary outcome: 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 — 1; 0; 1 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Dasatinib (Drug)
- Age
- Adult, Older Adult · 20+ yrs
- Sex
- All
- Sponsor
- Bristol-Myers Squibb
- Primary completion
- Sep 2008
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| 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 |
1; 0; 1 | — |
| SECONDARY Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs (SAEs), Drug Related AEs and Discontinued Due to AEs |
0; 0; 0; 9; 3; 4 | — |
| SECONDARY Number of Participants With Grade 3 or 4 Hematology Abnormalities |
1; 0; 0; 0; 1; 2 | — |
| SECONDARY Number of Participants With Grade 3-4 Serum Chemistry Abnormalities |
0; 0; 1; 0; 0; 1 | — |
| SECONDARY Most Frequent Grade 3-4 Hematology Abnormalities Occurring in >=10% Participants: Low Lymphocyte Count |
0; 1; 2 | — |
| SECONDARY Most Frequent Serum Chemistry Laboratory Abnormalities Occurring in >=10% Participants: High Magnesium |
1; 0; 1 | — |
| SECONDARY Number of Participants With Clinically Meaningful Physical Examination Measures |
— | — |
| SECONDARY Number of Participants With Clinically Meaningful Vital Signs |
0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings |
0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Change in QT Interval Corrected for Heart Rate (QTcF) |
0; 0; 0 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Dasatinib |
139.83; 127.1; 124.48; 137.03; 166.43; 102.61 | — |
| SECONDARY Area Under the Plasma-concentration-time Curve [AUC (INF)] of Dasatinib on Day 1 |
537.98; 544.36; 595.62 | — |
| SECONDARY AUC[TAU] of Dasatinib |
524.55; 530.81; 528.65; 499.69; 694.90; 716.27 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration of Dasatinib (Tmax) |
1.0; 1.0; 1.3; 1.0; 1.0; 2.3 | — |
| SECONDARY Terminal Elimination Half-life (T-half) of Dasatinib |
4.77; 4.68; 7.62; 5.75; 5.04; 7.95 | — |
| SECONDARY Accumulation Index (AI) of Dasatinib |
0.81; 1.78; 2.30; 1.12; 0.48; 1.72 | — |
| SECONDARY Mean Apparent Oral Clearance (CLo) of Dasatinib |
200.12; 215.86; 279.22; 135.36; 549.26; 374.30 | — |
| SECONDARY Mean Apparent Volume of Distribution (Vz/F) of Dasatinib |
1156.57; 1285.05; 2903.18; 566.93; 3443.56; 3362.08 | — |
| SECONDARY Cmax of Metabolite BMS-582691 |
5.18; 2.89; 7.90; 4.63; 4.61; 5.99 | — |
| SECONDARY AUC (0-t) of Metabolite BMS-582691 |
21.24; 5.99; 36.96; 15.24; 26.05; 37.65 | — |
| SECONDARY Tmax of the Metabolite BMS-582691 |
1.5; 1.5; 2.0; 1.0; 1.8; 3.0 | — |
| SECONDARY Mean Urine Concentration of Urinary N-telopeptide Type 1 Collagen (NTx) Biological Marker |
51.71; 62.57; 103.90; 51.55; 36.47; 51.33 | — |
| SECONDARY Mean Urine Concentration of Deoxypyridinoline (Dpyr) Biological Marker |
37.79; 50.37; 116.85; 27.08; 25.37; 46.73 | — |
| SECONDARY Mean Serum Concentration of Tartrate-resistant Acid Phosphatase Isoform 5b (TRACP-5b) Biological Marker |
5.13; 4.13; 3.40 | — |
| SECONDARY Mean Serum Concentration of Bone Alkaline Phosphatase (BAP) Biological Marker |
29.11; 32.34; 28.20 | — |
| SECONDARY Number of Participants With Sarcoma (Src) and Phosphorylated Src (pSRc) Protein Expression in Peripheral Blood Mononuclear Cells (PBMC) |
— | — |
| SECONDARY Number of Participants With Complete Response (CR) or Partial Response (PR) |
0; 0; 0; 0; 0; 0 | — |
Summary
The primary objective of this study is to determine the maximum tolerated dose (MTD) or the maximum administered dose (MAD) of Dasatinib (BMS-354825) in patients in Japan.
Eligibility Criteria
Inclusion Criteria
- Performance status (general conditions) specified by the Eastern Cooperative Oncology Group: 0-2
- Histologic or cytologic diagnosis of a solid tumor which has progressed on or following standard therapies (including relapsed disease) or for which no standard therapy exists.
- men and women, ages 20 and over
- women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 3 months after the study in such a manner that the risk of pregnancy is minimized
- Adequate hepatic function
Exclusion Criteria
- Participants who are eligible and willing to undergo transplantation at pre- study.
- Women who are pregnant or breastfeeding with known brain metastasis or symptoms of brain metastasis
- Uncontrolled or significant bleeding disorder unrelated to a primary tumor
- Dementia or mental illness that would prohibit understanding or giving informed consent.
- Severe allergy to drugs required for appropriate supportive care of patients in this study.
- History of gastrointestinal surgery or of any digestive disorder which has the potential to inhibit absorption of the study drug.
- Pleural effusion > Grade 1
- Patient with dysphagia
- Does not agree to blood/blood products transfusion(s)
- Donated blood over 200 mL within 4 weeks prior to the start of study therapy
- Medication that known to have a risk of causing Torsade de pointes
- Participants who are compulsorily detained for legal reasons or treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
Data sourced from ClinicalTrials.gov (NCT00339144). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.