Clinical trial NCT00339144: Study of Dasatinib (BMS-354825) in Patients With Solid Tumors
Official title: A Phase I Study of BMS-354825 in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tumors
Keywords: Solid tumors (including relapsed disease) that are refractory to standard therapies or for which no effective standard therapy exists
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2006-06-20
Enrollment: 16
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: 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
timeFrame: From start of the treatment i.e.Day 1 to end of Cycle 1 i.e. Day 30 (4 weeks)
Secondary outcomes:
measure: Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs (SAEs), Drug Related AEs and Discontinued Due to AEs
timeFrame: From start of study drug therapy up to 30 days after the last dose.
measure: Number of Participants With Grade 3 or 4 Hematology Abnormalities
timeFrame: From start of study drug therapy up to 30 days after the last dose.
measure: Number of Participants With Grade 3-4 Serum Chemistry Abnormalities
timeFrame: From start of study drug therapy up to 30 days after the last dose.
measure: Most Frequent Grade 3-4 Hematology Abnormalities Occurring in >=10% Participants: Low Lymphocyte Count
timeFrame: From start of study drug therapy up to 30 days after the last dose.
measure: Most Frequent Serum Chemistry Laboratory Abnormalities Occurring in >=10% Participants: High Magnesium
timeFrame: From start of study drug therapy up to 30 days after the last dose.
measure: Number of Participants With Clinically Meaningful Physical Examination Measures
timeFrame: From screening, Day 1 in each treatment course and at the end of study
measure: Number of Participants With Clinically Meaningful Vital Signs
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
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings
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
measure: Number of Participants With Clinically Significant Change in QT Interval Corrected for Heart Rate (QTcF)
timeFrame: Baseline, Day 1, Day 14 and Day 28
measure: Maximum Plasma Concentration (Cmax) of Dasatinib
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
measure: Area Under the Plasma-concentration-time Curve [AUC (INF)] of Dasatinib on Day 1
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
measure: AUC[TAU] of Dasatinib
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
measure: Time to Reach Maximum Observed Plasma Concentration of Dasatinib (Tmax)
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
measure: Terminal Elimination Half-life (T-half) of Dasatinib
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
measure: Accumulation Index (AI) of Dasatinib
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
measure: Mean Apparent Oral Clearance (CLo) of Dasatinib
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
measure: Mean Apparent Volume of Distribution (Vz/F) of Dasatinib
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
measure: Cmax of Metabolite BMS-582691
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
measure: AUC (0-t) of Metabolite BMS-582691
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
measure: Tmax of the Metabolite BMS-582691
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
measure: Mean Urine Concentration of Urinary N-telopeptide Type 1 Collagen (NTx) Biological Marker
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.
measure: Mean Urine Concentration of Deoxypyridinoline (Dpyr) Biological Marker
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
measure: Mean Serum Concentration of Tartrate-resistant Acid Phosphatase Isoform 5b (TRACP-5b) Biological Marker
timeFrame: Serum samples were assessed at baseline (Day -1) and on Days 14 and 28
measure: Mean Serum Concentration of Bone Alkaline Phosphatase (BAP) Biological Marker
timeFrame: Serum samples were assessed on baseline (Day -1), and pre-dose on Days 14, 28
measure: Number of Participants With Sarcoma (Src) and Phosphorylated Src (pSRc) Protein Expression in Peripheral Blood Mononuclear Cells (PBMC)
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
measure: Number of Participants With Complete Response (CR) or Partial Response (PR)
timeFrame: Within 4 weeks of first study drug administration, thereafter recorded every 4 or 8 weeks.
Other outcomes:
Locations:
city: Osakasayama City
country: Japan
facility: Local Institution
state: Osaka
city: Koto-Ku
country: Japan
facility: Local Institution
state: Tokyo
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: