Trial Outcomes & Findings for Phase I Study of Dasatinib (BMS-354825) and Capecitabine for Women With Advanced Breast Cancer (NCT NCT00452673)
NCT ID: NCT00452673
Last Updated: 2015-03-24
Results Overview
Safety was assessed from first dose of study drug through at least 30 days after the last dose, until resolution of drug-related toxicity or when toxicity was deemed irreversible, whichever was longer. An adverse event (AE) was considered a dose limiting toxicity (DLT) if it occurred in the first 21 days and was at least possibly related to study drugs and were: Clinically-evident toxicity of Grade \>= 3, or of Grade 2 which required interruption of treatment for \>= 7 days (consecutive or non-consecutive); non-hematologic abnormal laboratory value of Grade \>= 3, or hematologic toxicity of Grade 4, which persisted 7 days; any grade toxicity which in the judgment of the investigator required a dose reduction or removal from further study therapy.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
52 participants
Primary outcome timeframe
Day 1 to 30 days post last dose
Results posted on
2015-03-24
Participant Flow
28 Jan 2007 to 30 Oct 2012. Women with advanced breast cancer (ABC) were enrolled.
57 enrolled and 52 treated. Reasons for not being treated: 4 no longer met criteria; 1 administrative reason by sponsor. Drug was administered at a reduced dose (gradually escalating at each dose level) during the escalation period and then once a dose for the expansion cohort was identified, additional participants were treated with this dose.
Participant milestones
| Measure |
50 mg Dasatinib + 825 mg/m^2Capecitabine (Dose Escalation)
Dose Level 1: 50 milligram (mg) dasatinib oral tablet twice daily (BID) plus 825 mg per meter squared (m\^2) capecitabine oral tablet BID. Participants were treated at each dose level (DL) for minimum of 21 days before accrual to the next DL. Rules for dose escalation: If 0 dose level toxicity (DLT) was observed in the first 3 participants in a cohort, the next higher cohort was opened to accrual. If 1 DLT was observed in the first 3 participants in a cohort, then 3 additional participants were studied. If 0 DLT was observed in those 3 (ie, 1 DLT in 6 subjects at the DL), the next higher cohort was opened for accrual. If \>=2 DLT was observed in up to 6 subjects, then the maximum tolerated dose (MTD) was exceeded and the next lower DL was defined as the MTD. If 0 DLT was observed in 6 participants in a cohort and the next higher DL exceeded the MTD, then intermediate DLs would be studied. Once the MTD was determined, additional participants were enrolled into that dose group.
|
70 mg Dasatinib + 825 mg/m^2Capecitabine (Dose Escalation)
Dose Level 2: 70 mg dasatinib oral tablet BID plus 825 mg/m\^2 capecitabine oral tablet BID.
|
70 mg Dasatinib + 1000 mg/m^2Capecitabine (Dose Escalation)
Dose Level 3: 70 mg dasatinib oral tablet BID plus 1000 mg/m\^2 capecitabine oral tablet BID.
|
100 mg Dasatinib + 1000 mg/m^2Capecitabine (Dose Escalation)
Dose Level 3A: 100 mg dasatinib oral tablet once daily (QD) plus 1000 mg/m\^2 capecitabine oral tablet BID. No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for expansion in order to provide additional information regarding good tolerance of extended treatment.
|
100 mg Dasatinib + 1000 mg/m^2Capecitabine (Dose Expansion)
No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for the dose expansion period in order to provide additional information regarding good tolerance of extended treatment. An additional 21 participants were treated in this arm in the Dose Expansion Period.
|
|---|---|---|---|---|---|
|
Dose Escalation Period
STARTED
|
7
|
9
|
6
|
9
|
0
|
|
Dose Escalation Period
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Dose Escalation Period
NOT COMPLETED
|
7
|
9
|
6
|
9
|
0
|
|
Dose Expansion Period
STARTED
|
0
|
0
|
0
|
0
|
21
|
|
Dose Expansion Period
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Dose Expansion Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
21
|
Reasons for withdrawal
| Measure |
50 mg Dasatinib + 825 mg/m^2Capecitabine (Dose Escalation)
Dose Level 1: 50 milligram (mg) dasatinib oral tablet twice daily (BID) plus 825 mg per meter squared (m\^2) capecitabine oral tablet BID. Participants were treated at each dose level (DL) for minimum of 21 days before accrual to the next DL. Rules for dose escalation: If 0 dose level toxicity (DLT) was observed in the first 3 participants in a cohort, the next higher cohort was opened to accrual. If 1 DLT was observed in the first 3 participants in a cohort, then 3 additional participants were studied. If 0 DLT was observed in those 3 (ie, 1 DLT in 6 subjects at the DL), the next higher cohort was opened for accrual. If \>=2 DLT was observed in up to 6 subjects, then the maximum tolerated dose (MTD) was exceeded and the next lower DL was defined as the MTD. If 0 DLT was observed in 6 participants in a cohort and the next higher DL exceeded the MTD, then intermediate DLs would be studied. Once the MTD was determined, additional participants were enrolled into that dose group.
|
70 mg Dasatinib + 825 mg/m^2Capecitabine (Dose Escalation)
Dose Level 2: 70 mg dasatinib oral tablet BID plus 825 mg/m\^2 capecitabine oral tablet BID.
|
70 mg Dasatinib + 1000 mg/m^2Capecitabine (Dose Escalation)
Dose Level 3: 70 mg dasatinib oral tablet BID plus 1000 mg/m\^2 capecitabine oral tablet BID.
|
100 mg Dasatinib + 1000 mg/m^2Capecitabine (Dose Escalation)
Dose Level 3A: 100 mg dasatinib oral tablet once daily (QD) plus 1000 mg/m\^2 capecitabine oral tablet BID. No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for expansion in order to provide additional information regarding good tolerance of extended treatment.
|
100 mg Dasatinib + 1000 mg/m^2Capecitabine (Dose Expansion)
No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for the dose expansion period in order to provide additional information regarding good tolerance of extended treatment. An additional 21 participants were treated in this arm in the Dose Expansion Period.
|
|---|---|---|---|---|---|
|
Dose Escalation Period
Disease Progression
|
6
|
6
|
2
|
6
|
0
|
|
Dose Escalation Period
study drug toxicity
|
1
|
3
|
3
|
1
|
0
|
|
Dose Escalation Period
Other
|
0
|
0
|
1
|
0
|
0
|
|
Dose Escalation Period
Adverse Event
|
0
|
0
|
0
|
1
|
0
|
|
Dose Escalation Period
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
0
|
|
Dose Expansion Period
Disease Progression
|
0
|
0
|
0
|
0
|
19
|
|
Dose Expansion Period
Other
|
0
|
0
|
0
|
0
|
2
|
Baseline Characteristics
Phase I Study of Dasatinib (BMS-354825) and Capecitabine for Women With Advanced Breast Cancer
Baseline characteristics by cohort
| Measure |
50 mg Dasatinib + 825 mg/m^2Capecitabine
n=7 Participants
Dose Level 1: 50 milligram (mg) dasatinib oral tablet twice daily (BID) plus 825 mg per meter squared (m\^2) capecitabine oral tablet BID. Participants were treated at each dose level (DL) for minimum of 21 days before accrual to the next DL. Rules for dose escalation: If 0 dose level toxicity (DLT) was observed in the first 3 participants in a cohort, the next higher cohort was opened to accrual. If 1 DLT was observed in the first 3 participants in a cohort, then 3 additional participants were studied. If 0 DLT was observed in those 3 (ie, 1 DLT in 6 subjects at the DL), the next higher cohort was opened for accrual. If \>=2 DLT was observed in up to 6 subjects, then the maximum tolerated dose (MTD) was exceeded and the next lower DL was defined as the MTD. If 0 DLT was observed in 6 participants in a cohort and the next higher DL exceeded the MTD, then intermediate DLs would be studied. Once the MTD was determined, additional participants were enrolled into that dose group.
|
70 mg Dasatinib + 825 mg/m^2Capecitabine
n=9 Participants
Dose Level 2: 70 mg dasatinib oral tablet BID plus 825 mg/m\^2 capecitabine oral tablet BID.
|
70 mg Dasatinib + 1000 mg/m^2Capecitabine
n=6 Participants
Dose level 3: 70 mg dasatinib oral tablet BID plus 1000 mg/m\^2 capecitabine oral tablet BID.
|
100 mg Dasatinib + 1000 mg/m^2Capecitabine
n=30 Participants
Dose level 3A: 100 mg dasatinib oral tablet QD plus 1000 mg/m\^2 capecitabine oral tablet BID. No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for expansion in order to provide additional information regarding good tolerance of extended treatment.
|
Total
n=52 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
50.1 years
STANDARD_DEVIATION 10.02 • n=5 Participants
|
56.2 years
STANDARD_DEVIATION 15.52 • n=7 Participants
|
49.5 years
STANDARD_DEVIATION 10.78 • n=5 Participants
|
54.2 years
STANDARD_DEVIATION 10.91 • n=4 Participants
|
53.5 years
STANDARD_DEVIATION 11.56 • n=21 Participants
|
|
Age, Customized
< 50 years
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
12 participants
n=4 Participants
|
20 participants
n=21 Participants
|
|
Age, Customized
>= 50 years
|
5 participants
n=5 Participants
|
6 participants
n=7 Participants
|
3 participants
n=5 Participants
|
18 participants
n=4 Participants
|
32 participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
52 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
17 participants
n=4 Participants
|
29 participants
n=21 Participants
|
|
Region of Enrollment
Spain
|
2 participants
n=5 Participants
|
6 participants
n=7 Participants
|
2 participants
n=5 Participants
|
11 participants
n=4 Participants
|
21 participants
n=21 Participants
|
|
Region of Enrollment
Italy
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
2 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1 to 30 days post last dosePopulation: Safety Population: All participants who received at least one dose of study drug. DLTs: Grade 3 headache, Grade 3 pneumonia, Grade 3 diarrhea in Dosing arms, 1, 2, and 3, respectively. DLTs in dose arm 4: 1 participant with Grade 3 pneumonia and pain and 1 participant with Grade 4 neutropenia and diarrhea plus Grade 3 vomiting and mucositis.
Safety was assessed from first dose of study drug through at least 30 days after the last dose, until resolution of drug-related toxicity or when toxicity was deemed irreversible, whichever was longer. An adverse event (AE) was considered a dose limiting toxicity (DLT) if it occurred in the first 21 days and was at least possibly related to study drugs and were: Clinically-evident toxicity of Grade \>= 3, or of Grade 2 which required interruption of treatment for \>= 7 days (consecutive or non-consecutive); non-hematologic abnormal laboratory value of Grade \>= 3, or hematologic toxicity of Grade 4, which persisted 7 days; any grade toxicity which in the judgment of the investigator required a dose reduction or removal from further study therapy.
Outcome measures
| Measure |
50 mg Dasatinib + 825 mg/m^2Capecitabine
n=7 Participants
Dose Level 1: 50 milligram (mg) dasatinib oral tablet twice daily (BID) plus 825 mg per meter squared (m\^2) capecitabine oral tablet BID. Participants were treated at each dose level (DL) for minimum of 21 days before accrual to the next DL. Rules for dose escalation: If 0 dose level toxicity (DLT) was observed in the first 3 participants in a cohort, the next higher cohort was opened to accrual. If 1 DLT was observed in the first 3 participants in a cohort, then 3 additional participants were studied. If 0 DLT was observed in those 3 (ie, 1 DLT in 6 subjects at the DL), the next higher cohort was opened for accrual. If \>=2 DLT was observed in up to 6 subjects, then the maximum tolerated dose (MTD) was exceeded and the next lower DL was defined as the MTD. If 0 DLT was observed in 6 participants in a cohort and the next higher DL exceeded the MTD, then intermediate DLs would be studied. Once the MTD was determined, additional participants were enrolled into that dose group.
|
70 mg Dasatinib + 825 mg/m^2Capecitabine
n=9 Participants
Dose Level 2: 70 mg dasatinib oral tablet BID plus 825 mg/m\^2 capecitabine oral tablet BID.
|
70 mg Dasatinib + 1000 mg/m^2Capecitabine
n=6 Participants
Dose level 3: 70 mg dasatinib oral tablet BID plus 1000 mg/m\^2 capecitabine oral tablet BID.
|
100 mg Dasatinib + 1000 mg/m^2Capecitabine
n=30 Participants
Dose level 3A: 100 mg dasatinib oral tablet QD plus 1000 mg/m\^2 capecitabine oral tablet BID. No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for expansion in order to provide additional information regarding good tolerance of extended treatment.
|
|---|---|---|---|---|
|
Number of Participants With Dose Limiting Toxicities Per Dose Level - Safety Population
|
1 participants
|
1 participants
|
1 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Day 1 up to 30 days post last dosePopulation: Safety Population: all participants receiving at least one dose of study drug.
Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious AE (SAE)=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
Outcome measures
| Measure |
50 mg Dasatinib + 825 mg/m^2Capecitabine
n=7 Participants
Dose Level 1: 50 milligram (mg) dasatinib oral tablet twice daily (BID) plus 825 mg per meter squared (m\^2) capecitabine oral tablet BID. Participants were treated at each dose level (DL) for minimum of 21 days before accrual to the next DL. Rules for dose escalation: If 0 dose level toxicity (DLT) was observed in the first 3 participants in a cohort, the next higher cohort was opened to accrual. If 1 DLT was observed in the first 3 participants in a cohort, then 3 additional participants were studied. If 0 DLT was observed in those 3 (ie, 1 DLT in 6 subjects at the DL), the next higher cohort was opened for accrual. If \>=2 DLT was observed in up to 6 subjects, then the maximum tolerated dose (MTD) was exceeded and the next lower DL was defined as the MTD. If 0 DLT was observed in 6 participants in a cohort and the next higher DL exceeded the MTD, then intermediate DLs would be studied. Once the MTD was determined, additional participants were enrolled into that dose group.
|
70 mg Dasatinib + 825 mg/m^2Capecitabine
n=9 Participants
Dose Level 2: 70 mg dasatinib oral tablet BID plus 825 mg/m\^2 capecitabine oral tablet BID.
|
70 mg Dasatinib + 1000 mg/m^2Capecitabine
n=6 Participants
Dose level 3: 70 mg dasatinib oral tablet BID plus 1000 mg/m\^2 capecitabine oral tablet BID.
|
100 mg Dasatinib + 1000 mg/m^2Capecitabine
n=30 Participants
Dose level 3A: 100 mg dasatinib oral tablet QD plus 1000 mg/m\^2 capecitabine oral tablet BID. No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for expansion in order to provide additional information regarding good tolerance of extended treatment.
|
|---|---|---|---|---|
|
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, Adverse Events Leading to Discontinuation and Treatment-related Adverse Events - Safety Population
Deaths within 30 days of last dose
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, Adverse Events Leading to Discontinuation and Treatment-related Adverse Events - Safety Population
Deaths reported beyond 30 days post last dose
|
0 participants
|
0 participants
|
0 participants
|
4 participants
|
|
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, Adverse Events Leading to Discontinuation and Treatment-related Adverse Events - Safety Population
Participants with SAEs
|
2 participants
|
2 participants
|
4 participants
|
13 participants
|
|
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, Adverse Events Leading to Discontinuation and Treatment-related Adverse Events - Safety Population
Participants with Grade 3 - 4 SAEs
|
2 participants
|
1 participants
|
4 participants
|
11 participants
|
|
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, Adverse Events Leading to Discontinuation and Treatment-related Adverse Events - Safety Population
Participants with AEs
|
7 participants
|
9 participants
|
6 participants
|
30 participants
|
|
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, Adverse Events Leading to Discontinuation and Treatment-related Adverse Events - Safety Population
AEs leading to discontinuation of therapy
|
2 participants
|
3 participants
|
4 participants
|
4 participants
|
|
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, Adverse Events Leading to Discontinuation and Treatment-related Adverse Events - Safety Population
Participants with study drug-related AEs
|
7 participants
|
9 participants
|
6 participants
|
28 participants
|
SECONDARY outcome
Timeframe: Day 1 to 30 days post last dosePopulation: All participants with at least one measurable lesion at baseline, who received at least one dose of the combination therapy and have at least one on-study tumor assessment or stopped study treatment prior to first assessment, were evaluated. Those who stopped drug prior to tumor assessment for reasons unrelated to disease or drug were excluded.
Complete Response (CR): disappearance of all target and non-target lesions, with confirmation at \>=4 weeks interval; Partial Response (PR): \>= 30% decrease in sum of longest diameter (LDs) of target lesions, taking as reference the baseline sum LD, with confirmation at \>= 4 weeks interval. Progressive Disease (PD): Appearance of new lesion(s), or \>=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, without unequivocal progression of non-target lesions, after \>=6 weeks on study. Radiological tumor assessment by computed tomography (CT) or magnetic resonance imaging (MRI) occurred every 6 weeks. For those patients who were on treatment \> 24 weeks, the tumor assessment occurred every 9 weeks.
Outcome measures
| Measure |
50 mg Dasatinib + 825 mg/m^2Capecitabine
n=4 Participants
Dose Level 1: 50 milligram (mg) dasatinib oral tablet twice daily (BID) plus 825 mg per meter squared (m\^2) capecitabine oral tablet BID. Participants were treated at each dose level (DL) for minimum of 21 days before accrual to the next DL. Rules for dose escalation: If 0 dose level toxicity (DLT) was observed in the first 3 participants in a cohort, the next higher cohort was opened to accrual. If 1 DLT was observed in the first 3 participants in a cohort, then 3 additional participants were studied. If 0 DLT was observed in those 3 (ie, 1 DLT in 6 subjects at the DL), the next higher cohort was opened for accrual. If \>=2 DLT was observed in up to 6 subjects, then the maximum tolerated dose (MTD) was exceeded and the next lower DL was defined as the MTD. If 0 DLT was observed in 6 participants in a cohort and the next higher DL exceeded the MTD, then intermediate DLs would be studied. Once the MTD was determined, additional participants were enrolled into that dose group.
|
70 mg Dasatinib + 825 mg/m^2Capecitabine
n=6 Participants
Dose Level 2: 70 mg dasatinib oral tablet BID plus 825 mg/m\^2 capecitabine oral tablet BID.
|
70 mg Dasatinib + 1000 mg/m^2Capecitabine
n=5 Participants
Dose level 3: 70 mg dasatinib oral tablet BID plus 1000 mg/m\^2 capecitabine oral tablet BID.
|
100 mg Dasatinib + 1000 mg/m^2Capecitabine
n=25 Participants
Dose level 3A: 100 mg dasatinib oral tablet QD plus 1000 mg/m\^2 capecitabine oral tablet BID. No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for expansion in order to provide additional information regarding good tolerance of extended treatment.
|
|---|---|---|---|---|
|
Number of Participants With Overall Response to Tumor - Efficacy Evaluable Population
Complete Response
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Overall Response to Tumor - Efficacy Evaluable Population
Unconfirmed partial response
|
1 participants
|
1 participants
|
1 participants
|
3 participants
|
|
Number of Participants With Overall Response to Tumor - Efficacy Evaluable Population
Partial Response
|
2 participants
|
1 participants
|
0 participants
|
6 participants
|
|
Number of Participants With Overall Response to Tumor - Efficacy Evaluable Population
Stable Disease
|
0 participants
|
1 participants
|
2 participants
|
11 participants
|
|
Number of Participants With Overall Response to Tumor - Efficacy Evaluable Population
Progressive Disease
|
1 participants
|
2 participants
|
2 participants
|
3 participants
|
|
Number of Participants With Overall Response to Tumor - Efficacy Evaluable Population
Clinical Progression
|
0 participants
|
1 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Overall Response to Tumor - Efficacy Evaluable Population
Discontinuation due to study drug toxicity
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Day 1 up to 30 days post last dosePopulation: n=number of participants with ORR: 2, 1, 0, 6 in dosing arms 1, 2, 3, and 4, respectively. n= number of participants with Disease control: 3, 2, 2, 14 in dosing arms 1, 2, 3, and 4, respectively.
Objective response rate was the percentage of participants, (n/N; number with objective response per Number evaluated) whose best response is either a Complete Response (CR) or a Partial Response (PR). Disease control rate was defined as percentage (n/N) of participants with stable disease greater than (\>) 6 months, PR, or CR. Efficacy Evaluable Population: All participants with at least one measurable lesion at baseline, who received at least one dose of combination study drug and have at least one on-study tumor assessment or stopped study treatment prior to first assessment, were evaluated. Those who stop treatment prior to tumor assessment for reasons unrelated to disease or drug were excluded.
Outcome measures
| Measure |
50 mg Dasatinib + 825 mg/m^2Capecitabine
n=4 Participants
Dose Level 1: 50 milligram (mg) dasatinib oral tablet twice daily (BID) plus 825 mg per meter squared (m\^2) capecitabine oral tablet BID. Participants were treated at each dose level (DL) for minimum of 21 days before accrual to the next DL. Rules for dose escalation: If 0 dose level toxicity (DLT) was observed in the first 3 participants in a cohort, the next higher cohort was opened to accrual. If 1 DLT was observed in the first 3 participants in a cohort, then 3 additional participants were studied. If 0 DLT was observed in those 3 (ie, 1 DLT in 6 subjects at the DL), the next higher cohort was opened for accrual. If \>=2 DLT was observed in up to 6 subjects, then the maximum tolerated dose (MTD) was exceeded and the next lower DL was defined as the MTD. If 0 DLT was observed in 6 participants in a cohort and the next higher DL exceeded the MTD, then intermediate DLs would be studied. Once the MTD was determined, additional participants were enrolled into that dose group.
|
70 mg Dasatinib + 825 mg/m^2Capecitabine
n=6 Participants
Dose Level 2: 70 mg dasatinib oral tablet BID plus 825 mg/m\^2 capecitabine oral tablet BID.
|
70 mg Dasatinib + 1000 mg/m^2Capecitabine
n=5 Participants
Dose level 3: 70 mg dasatinib oral tablet BID plus 1000 mg/m\^2 capecitabine oral tablet BID.
|
100 mg Dasatinib + 1000 mg/m^2Capecitabine
n=25 Participants
Dose level 3A: 100 mg dasatinib oral tablet QD plus 1000 mg/m\^2 capecitabine oral tablet BID. No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for expansion in order to provide additional information regarding good tolerance of extended treatment.
|
|---|---|---|---|---|
|
Objective Response Rate (ORR) and Disease Control Rate - Efficacy Evaluable Population
Objective Response Rate
|
50.0 percentage of participants
Interval 6.76 to 93.24
|
16.67 percentage of participants
Interval 0.42 to 64.12
|
0 percentage of participants
participants=0 so percentage is less than 0 and a Confidence interval is not appropriate.
|
24.0 percentage of participants
Interval 9.36 to 45.13
|
|
Objective Response Rate (ORR) and Disease Control Rate - Efficacy Evaluable Population
Disease control rate
|
75.0 percentage of participants
Interval 19.41 to 99.37
|
33.33 percentage of participants
Interval 4.33 to 77.72
|
40.0 percentage of participants
Interval 5.27 to 85.34
|
56.00 percentage of participants
Interval 34.93 to 75.6
|
SECONDARY outcome
Timeframe: Day 1 up to 30 days post last dosePopulation: Safety Population: All participants with at least 1 dose of study drug. N=number of participants with Grade 0 values at baseline in each dosing arm, respectively.
National Cancer Institute Common terminology criteria (CTC), Version 3 used to assess parameters. Lower limit of normal (LLN). CTC criteria: Absolute neutrophil count (ANC). Leukocytes (White blood cells) Grade (Gr) 1:\<LLN to 3.0\*10\^9/L, Gr 2:\<3.0 to 2.0\*10\^9/L, Gr 3:\<2.0 to 1.0\*10\^9/L, Gr 4:\<1.0\*10\^9/L. ANC Gr 1:\<LLN to 1.5\*10\^9/L, Gr 2:\<1.5 to 1.0\*10\^9/L, Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L. Platelet count Gr 1:LLN to 75.0\*10\^9/L, Gr 2:\<75.0 to 50.0\*10\^9/L, Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L. Hemoglobin Gr 1:\<LLN to 10.0 g/dL, Gr 2:\<10.0 to 8.0 g/dL, Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL. Participants with a baseline hematology lab value of Gr 0 but who had Gr 3 - 4 hematology value while on-study are presented below.
Outcome measures
| Measure |
50 mg Dasatinib + 825 mg/m^2Capecitabine
n=7 Participants
Dose Level 1: 50 milligram (mg) dasatinib oral tablet twice daily (BID) plus 825 mg per meter squared (m\^2) capecitabine oral tablet BID. Participants were treated at each dose level (DL) for minimum of 21 days before accrual to the next DL. Rules for dose escalation: If 0 dose level toxicity (DLT) was observed in the first 3 participants in a cohort, the next higher cohort was opened to accrual. If 1 DLT was observed in the first 3 participants in a cohort, then 3 additional participants were studied. If 0 DLT was observed in those 3 (ie, 1 DLT in 6 subjects at the DL), the next higher cohort was opened for accrual. If \>=2 DLT was observed in up to 6 subjects, then the maximum tolerated dose (MTD) was exceeded and the next lower DL was defined as the MTD. If 0 DLT was observed in 6 participants in a cohort and the next higher DL exceeded the MTD, then intermediate DLs would be studied. Once the MTD was determined, additional participants were enrolled into that dose group.
|
70 mg Dasatinib + 825 mg/m^2Capecitabine
n=9 Participants
Dose Level 2: 70 mg dasatinib oral tablet BID plus 825 mg/m\^2 capecitabine oral tablet BID.
|
70 mg Dasatinib + 1000 mg/m^2Capecitabine
n=6 Participants
Dose level 3: 70 mg dasatinib oral tablet BID plus 1000 mg/m\^2 capecitabine oral tablet BID.
|
100 mg Dasatinib + 1000 mg/m^2Capecitabine
n=30 Participants
Dose level 3A: 100 mg dasatinib oral tablet QD plus 1000 mg/m\^2 capecitabine oral tablet BID. No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for expansion in order to provide additional information regarding good tolerance of extended treatment.
|
|---|---|---|---|---|
|
Number of Participants On-Study With Grade 3 - 4 Hematology Laboratory Test Values in Those Participants With a Baseline Laboratory Value of Grade 0 - Safety Population
Platelet Count (N=7, 9, 6, 30)
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants On-Study With Grade 3 - 4 Hematology Laboratory Test Values in Those Participants With a Baseline Laboratory Value of Grade 0 - Safety Population
Leukocytes ( N=7, 9, 5, 29)
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants On-Study With Grade 3 - 4 Hematology Laboratory Test Values in Those Participants With a Baseline Laboratory Value of Grade 0 - Safety Population
ANC (N=6, 9, 6, 30)
|
0 participants
|
0 participants
|
0 participants
|
3 participants
|
|
Number of Participants On-Study With Grade 3 - 4 Hematology Laboratory Test Values in Those Participants With a Baseline Laboratory Value of Grade 0 - Safety Population
Hemoglobin (N=7, 6, 4, 18)
|
0 participants
|
0 participants
|
0 participants
|
3 participants
|
SECONDARY outcome
Timeframe: Day 1 to 30 days post last dosePopulation: Safety Population: All participants with at least 1 dose of study drug. N=number of participants with Grade 0 values at baseline in each dosing arm, respectively.
CTC, Version 3 used to assess parameters. (ULN)=upper limit of normal: (ALT)= alanine transaminase; (AST)=aspartate aminotransferase; (ALP)=alkaline phosphatase. ALT Grade (Gr)1:\>ULN to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. AST Gr 1: \>ULN to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. Total bilirubin Gr 1: \>ULN to 1.5\*ULN; Gr 2: \>1.5 to 3.0\*ULN; Gr 3: \>3.0 to 10.0\*ULN; Gr 4: \>10.0\*ULN. ALP (U/L) Gr1:\>ULN to 2.5\*ULN, Gr2:\>2.5 to 5.0\*ULN, Gr3:\>5.0 to 20.0\*ULN, Gr4:\>20.0\*ULN. Albumin (low) Gr 1:\<LLN - 3 grams per deciliter (g/dL)to \<LLN - 3 g/dL; Gr 2: \<3 - 2 g/dL to \< 3.0 - 2.0 g/dL; Gr 3: \< 2 g/dL to \<2 g/L. Participants with a baseline chemistry lab value of Gr 0 but who had Gr 3 - 4 chemistry value while on-study are presented below.
Outcome measures
| Measure |
50 mg Dasatinib + 825 mg/m^2Capecitabine
n=7 Participants
Dose Level 1: 50 milligram (mg) dasatinib oral tablet twice daily (BID) plus 825 mg per meter squared (m\^2) capecitabine oral tablet BID. Participants were treated at each dose level (DL) for minimum of 21 days before accrual to the next DL. Rules for dose escalation: If 0 dose level toxicity (DLT) was observed in the first 3 participants in a cohort, the next higher cohort was opened to accrual. If 1 DLT was observed in the first 3 participants in a cohort, then 3 additional participants were studied. If 0 DLT was observed in those 3 (ie, 1 DLT in 6 subjects at the DL), the next higher cohort was opened for accrual. If \>=2 DLT was observed in up to 6 subjects, then the maximum tolerated dose (MTD) was exceeded and the next lower DL was defined as the MTD. If 0 DLT was observed in 6 participants in a cohort and the next higher DL exceeded the MTD, then intermediate DLs would be studied. Once the MTD was determined, additional participants were enrolled into that dose group.
|
70 mg Dasatinib + 825 mg/m^2Capecitabine
n=9 Participants
Dose Level 2: 70 mg dasatinib oral tablet BID plus 825 mg/m\^2 capecitabine oral tablet BID.
|
70 mg Dasatinib + 1000 mg/m^2Capecitabine
n=6 Participants
Dose level 3: 70 mg dasatinib oral tablet BID plus 1000 mg/m\^2 capecitabine oral tablet BID.
|
100 mg Dasatinib + 1000 mg/m^2Capecitabine
n=30 Participants
Dose level 3A: 100 mg dasatinib oral tablet QD plus 1000 mg/m\^2 capecitabine oral tablet BID. No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for expansion in order to provide additional information regarding good tolerance of extended treatment.
|
|---|---|---|---|---|
|
Number of Participants On-study With Grade 3 - 4 Chemistry Laboratory Values in Those Participants With a Baseline Laboratory Value of Grade 0 - Safety Population
Alkaline Phosphatase (N=4, 6, 5, 21)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants On-study With Grade 3 - 4 Chemistry Laboratory Values in Those Participants With a Baseline Laboratory Value of Grade 0 - Safety Population
Alanine Aminotransferase (N=6, 9, 6, 25)
|
0 participants
|
0 participants
|
0 participants
|
2 participants
|
|
Number of Participants On-study With Grade 3 - 4 Chemistry Laboratory Values in Those Participants With a Baseline Laboratory Value of Grade 0 - Safety Population
Aspartate Aminotransferase (N=4, 8, 6, 25)
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants On-study With Grade 3 - 4 Chemistry Laboratory Values in Those Participants With a Baseline Laboratory Value of Grade 0 - Safety Population
Total Bilirubin (N=6, 9, 6, 29)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
50 mg Dasatinib + 825 mg/m^2 Capecitabine
Serious events: 2 serious events
Other events: 7 other events
Deaths: 0 deaths
70 mg Dasatinib + 825 mg/m^2 Capecitabine
Serious events: 2 serious events
Other events: 9 other events
Deaths: 0 deaths
70 mg Dasatinib + 1000 mg/m^2 Capecitabine
Serious events: 4 serious events
Other events: 6 other events
Deaths: 0 deaths
100 mg Dasatinib + 1000 mg/m^2 Capecitabine
Serious events: 13 serious events
Other events: 30 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
50 mg Dasatinib + 825 mg/m^2 Capecitabine
n=7 participants at risk
Dose Level 1: 50 milligram (mg) dasatinib oral tablet twice daily (BID) plus 825 mg per meter squared (m\^2) capecitabine oral tablet BID. Participants were treated at each dose level (DL) for minimum of 21 days before accrual to the next DL. Rules for dose escalation: If 0 dose level toxicity (DLT) was observed in the first 3 participants in a cohort, the next higher cohort was opened to accrual. If 1 DLT was observed in the first 3 participants in a cohort, then 3 additional participants were studied. If 0 DLT was observed in those 3 (ie, 1 DLT in 6 subjects at the DL), the next higher cohort was opened for accrual. If \>=2 DLT was observed in up to 6 subjects, then the maximum tolerated dose (MTD) was exceeded and the next lower DL was defined as the MTD. If 0 DLT was observed in 6 participants in a cohort and the next higher DL exceeded the MTD, then intermediate DLs would be studied. Once the MTD was determined, additional participants were enrolled into that dose group.
|
70 mg Dasatinib + 825 mg/m^2 Capecitabine
n=9 participants at risk
Dose Level 2: 70 mg dasatinib oral tablet BID plus 825 mg/m\^2 capecitabine oral tablet BID.
|
70 mg Dasatinib + 1000 mg/m^2 Capecitabine
n=6 participants at risk
Dose Level 3: 70 mg dasatinib oral tablet BID plus 1000 mg/m\^2 capecitabine oral tablet BID.
|
100 mg Dasatinib + 1000 mg/m^2 Capecitabine
n=30 participants at risk
Dose Level 3A: 100 mg dasatinib oral tablet once daily (QD) plus 1000 mg/m\^2 capecitabine oral tablet BID. No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for expansion in order to provide additional information regarding good tolerance of extended treatment.
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Mucosal inflammation
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Nervous system disorders
Syncope
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Infections and infestations
Upper respiratory tract infection
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Vomiting
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Nervous system disorders
Headache
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Infections and infestations
Infection
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Asthenia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Pyrexia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Chest pain
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Pain
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
33.3%
2/6 • Day 1 up to 30 days post last dose.
|
10.0%
3/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Diarrhoea
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
Other adverse events
| Measure |
50 mg Dasatinib + 825 mg/m^2 Capecitabine
n=7 participants at risk
Dose Level 1: 50 milligram (mg) dasatinib oral tablet twice daily (BID) plus 825 mg per meter squared (m\^2) capecitabine oral tablet BID. Participants were treated at each dose level (DL) for minimum of 21 days before accrual to the next DL. Rules for dose escalation: If 0 dose level toxicity (DLT) was observed in the first 3 participants in a cohort, the next higher cohort was opened to accrual. If 1 DLT was observed in the first 3 participants in a cohort, then 3 additional participants were studied. If 0 DLT was observed in those 3 (ie, 1 DLT in 6 subjects at the DL), the next higher cohort was opened for accrual. If \>=2 DLT was observed in up to 6 subjects, then the maximum tolerated dose (MTD) was exceeded and the next lower DL was defined as the MTD. If 0 DLT was observed in 6 participants in a cohort and the next higher DL exceeded the MTD, then intermediate DLs would be studied. Once the MTD was determined, additional participants were enrolled into that dose group.
|
70 mg Dasatinib + 825 mg/m^2 Capecitabine
n=9 participants at risk
Dose Level 2: 70 mg dasatinib oral tablet BID plus 825 mg/m\^2 capecitabine oral tablet BID.
|
70 mg Dasatinib + 1000 mg/m^2 Capecitabine
n=6 participants at risk
Dose Level 3: 70 mg dasatinib oral tablet BID plus 1000 mg/m\^2 capecitabine oral tablet BID.
|
100 mg Dasatinib + 1000 mg/m^2 Capecitabine
n=30 participants at risk
Dose Level 3A: 100 mg dasatinib oral tablet once daily (QD) plus 1000 mg/m\^2 capecitabine oral tablet BID. No dose level in this study was identified as the maximum tolerated dose (MDT) but this dose arm (100 mg dasatinib plus 1000 mg/m\^2 capecitabine) was selected for expansion in order to provide additional information regarding good tolerance of extended treatment.
|
|---|---|---|---|---|
|
Investigations
Aspartate aminotransferase
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
42.9%
3/7 • Day 1 up to 30 days post last dose.
|
44.4%
4/9 • Day 1 up to 30 days post last dose.
|
33.3%
2/6 • Day 1 up to 30 days post last dose.
|
20.0%
6/30 • Day 1 up to 30 days post last dose.
|
|
Metabolism and nutrition disorders
Dehydration
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Vascular disorders
Varicose vein
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Asthenia
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
44.4%
4/9 • Day 1 up to 30 days post last dose.
|
33.3%
2/6 • Day 1 up to 30 days post last dose.
|
40.0%
12/30 • Day 1 up to 30 days post last dose.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Abdominal pain
|
28.6%
2/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
10.0%
3/30 • Day 1 up to 30 days post last dose.
|
|
Nervous system disorders
Dysgeusia
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
16.7%
5/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Eye disorders
Eyelids pruritus
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Investigations
Haemoglobin
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Eye disorders
Lacrimation increased
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Mucosal inflammation
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
33.3%
2/6 • Day 1 up to 30 days post last dose.
|
16.7%
5/30 • Day 1 up to 30 days post last dose.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
13.3%
4/30 • Day 1 up to 30 days post last dose.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
20.0%
6/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Infections and infestations
Upper respiratory tract infection
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
22.2%
2/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Eye disorders
Vision blurred
|
28.6%
2/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
22.2%
2/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Chills
|
28.6%
2/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
33.3%
2/6 • Day 1 up to 30 days post last dose.
|
23.3%
7/30 • Day 1 up to 30 days post last dose.
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Eye disorders
Dry eye
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Lip dry
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Orthopnoea
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
28.6%
2/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Vomiting
|
42.9%
3/7 • Day 1 up to 30 days post last dose.
|
44.4%
4/9 • Day 1 up to 30 days post last dose.
|
33.3%
2/6 • Day 1 up to 30 days post last dose.
|
40.0%
12/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Psychiatric disorders
Anxiety
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
13.3%
4/30 • Day 1 up to 30 days post last dose.
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Constipation
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
33.3%
2/6 • Day 1 up to 30 days post last dose.
|
16.7%
5/30 • Day 1 up to 30 days post last dose.
|
|
Psychiatric disorders
Depression
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
22.2%
2/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
13.3%
4/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Fatigue
|
57.1%
4/7 • Day 1 up to 30 days post last dose.
|
22.2%
2/9 • Day 1 up to 30 days post last dose.
|
50.0%
3/6 • Day 1 up to 30 days post last dose.
|
30.0%
9/30 • Day 1 up to 30 days post last dose.
|
|
Nervous system disorders
Headache
|
71.4%
5/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
50.0%
3/6 • Day 1 up to 30 days post last dose.
|
20.0%
6/30 • Day 1 up to 30 days post last dose.
|
|
Psychiatric disorders
Insomnia
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
22.2%
2/9 • Day 1 up to 30 days post last dose.
|
33.3%
2/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Oedema peripheral
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
13.3%
4/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
28.6%
2/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
66.7%
4/6 • Day 1 up to 30 days post last dose.
|
63.3%
19/30 • Day 1 up to 30 days post last dose.
|
|
Renal and urinary disorders
Pollakiuria
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
16.7%
5/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
10.0%
3/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
22.2%
2/9 • Day 1 up to 30 days post last dose.
|
66.7%
4/6 • Day 1 up to 30 days post last dose.
|
30.0%
9/30 • Day 1 up to 30 days post last dose.
|
|
Infections and infestations
Ear infection
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Face oedema
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Nervous system disorders
Facial neuralgia
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Infections and infestations
Gingivitis
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Musculoskeletal and connective tissue disorders
Muscle tightness
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Pyrexia
|
42.9%
3/7 • Day 1 up to 30 days post last dose.
|
22.2%
2/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
26.7%
8/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Rash
|
42.9%
3/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
33.3%
2/6 • Day 1 up to 30 days post last dose.
|
16.7%
5/30 • Day 1 up to 30 days post last dose.
|
|
Eye disorders
Visual impairment
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Investigations
White blood cell count decreased
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
23.3%
7/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Chest pain
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Eye disorders
Diplopia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Nervous system disorders
Dizziness postural
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
22.2%
2/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Flatulence
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Vascular disorders
Hot flush
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Irritability
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
10.0%
3/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Oedema
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
General disorders
Pain
|
28.6%
2/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
13.3%
4/30 • Day 1 up to 30 days post last dose.
|
|
Eye disorders
Periorbital oedema
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
50.0%
3/6 • Day 1 up to 30 days post last dose.
|
23.3%
7/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
10.0%
3/30 • Day 1 up to 30 days post last dose.
|
|
Investigations
Weight decreased
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
13.3%
4/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Diarrhoea
|
28.6%
2/7 • Day 1 up to 30 days post last dose.
|
33.3%
3/9 • Day 1 up to 30 days post last dose.
|
50.0%
3/6 • Day 1 up to 30 days post last dose.
|
36.7%
11/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Dyspepsia
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
10.0%
3/30 • Day 1 up to 30 days post last dose.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Investigations
Heart rate increased
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Vascular disorders
Hypotension
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
6.7%
2/30 • Day 1 up to 30 days post last dose.
|
|
Investigations
Neutrophil count
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
42.9%
3/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
13.3%
4/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Plantar erythema
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Investigations
QRS axis abnormal
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Cardiac disorders
Tachycardia
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
10.0%
3/30 • Day 1 up to 30 days post last dose.
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Psychiatric disorders
Affect lability
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
16.7%
5/30 • Day 1 up to 30 days post last dose.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
16.7%
5/30 • Day 1 up to 30 days post last dose.
|
|
Nervous system disorders
Dizziness
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
33.3%
3/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
16.7%
5/30 • Day 1 up to 30 days post last dose.
|
|
Vascular disorders
Hypertension
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
28.6%
2/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
10.0%
3/30 • Day 1 up to 30 days post last dose.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Eye disorders
Keratitis
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
10.0%
3/30 • Day 1 up to 30 days post last dose.
|
|
Gastrointestinal disorders
Nausea
|
57.1%
4/7 • Day 1 up to 30 days post last dose.
|
55.6%
5/9 • Day 1 up to 30 days post last dose.
|
50.0%
3/6 • Day 1 up to 30 days post last dose.
|
63.3%
19/30 • Day 1 up to 30 days post last dose.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Skin and subcutaneous tissue disorders
Palmar erythema
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
16.7%
1/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
10.0%
3/30 • Day 1 up to 30 days post last dose.
|
|
Cardiac disorders
Pericardial effusion
|
14.3%
1/7 • Day 1 up to 30 days post last dose.
|
0.00%
0/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
10.0%
3/30 • Day 1 up to 30 days post last dose.
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
0.00%
0/30 • Day 1 up to 30 days post last dose.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/7 • Day 1 up to 30 days post last dose.
|
11.1%
1/9 • Day 1 up to 30 days post last dose.
|
0.00%
0/6 • Day 1 up to 30 days post last dose.
|
3.3%
1/30 • Day 1 up to 30 days post last dose.
|
Additional Information
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