Trial Outcomes & Findings for Phase I Study of Ixabepilone Plus Lapatinib With or Without Capecitabine in the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer (NCT NCT00634088)
NCT ID: NCT00634088
Last Updated: 2016-03-10
Results Overview
MTD is defined as the maximum dose that can be administered to 6 participants such that no more than 1 (or fewer than one third if more than 6 participants receive treatment) experiences a DLT, with at least 2 experiencing a DLT at the next higher dose level. The RP2D is based on the MTD and the assessment of any relevant chronic toxicities.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
13 participants
Primary outcome timeframe
Days 1 through 21
Results posted on
2016-03-10
Participant Flow
Of 13 participants enrolled, 10 received treatment with ixabepilone + lapatinib in escalating-dose cohorts. No participants were enrolled in the ixabepilone + lapatinib + capecitabine cohort due to premature termination of the study.
Participant milestones
| Measure |
Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg
Lapatinib, 1000 mg, administered daily in a lead-in period, orally once a day, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib administered daily, orally once a day, for 21-day cycle.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg
Initiated a minimum of 14 days following Day 1 of previous cohort (ixabepilone, 32 mg/m\^2 + lapatinib, 1000 mg). Lapatinib, 1250 mg, administered daily, orally once a day, for 7 to 14 consecutive days prior to the first administration of ixabepilone (Day 1). After the lapatinib lead-in phase, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib administered daily, orally once a day, for 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg
Initiated a minimum of 14 days following Day 1 of previous cohort (ixabepilone, 32 mg/m\^2 + lapatinib, 1250 mg). Lapatinib, 1250 mg, administered daily, orally once a day, for 7 to 14 consecutive days prior to the first administration of ixabepilone (Day 1). After the lapatinib lead-in phase, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib administered daily, orally once a day, for 21-day cycle.
|
Ixabepilone+ Lapatinib + Capecitabine
A triplet combination of ixabepilone, lapatinib, and capecitabine was planned for analysis in escalating doses but was not initiated due to premature termination of the study.
|
|---|---|---|---|---|
|
Time Period 1: Dose Level 1
STARTED
|
6
|
0
|
0
|
0
|
|
Time Period 1: Dose Level 1
COMPLETED
|
0
|
0
|
0
|
0
|
|
Time Period 1: Dose Level 1
NOT COMPLETED
|
6
|
0
|
0
|
0
|
|
Time Period 2: Dose Level 2
STARTED
|
0
|
3
|
0
|
0
|
|
Time Period 2: Dose Level 2
COMPLETED
|
0
|
0
|
0
|
0
|
|
Time Period 2: Dose Level 2
NOT COMPLETED
|
0
|
3
|
0
|
0
|
|
Time Period 3: Dose Level 3
STARTED
|
0
|
0
|
1
|
0
|
|
Time Period 3: Dose Level 3
COMPLETED
|
0
|
0
|
0
|
0
|
|
Time Period 3: Dose Level 3
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
Time Period 4: Triplet Combination
STARTED
|
0
|
0
|
0
|
0
|
|
Time Period 4: Triplet Combination
COMPLETED
|
0
|
0
|
0
|
0
|
|
Time Period 4: Triplet Combination
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg
Lapatinib, 1000 mg, administered daily in a lead-in period, orally once a day, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib administered daily, orally once a day, for 21-day cycle.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg
Initiated a minimum of 14 days following Day 1 of previous cohort (ixabepilone, 32 mg/m\^2 + lapatinib, 1000 mg). Lapatinib, 1250 mg, administered daily, orally once a day, for 7 to 14 consecutive days prior to the first administration of ixabepilone (Day 1). After the lapatinib lead-in phase, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib administered daily, orally once a day, for 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg
Initiated a minimum of 14 days following Day 1 of previous cohort (ixabepilone, 32 mg/m\^2 + lapatinib, 1250 mg). Lapatinib, 1250 mg, administered daily, orally once a day, for 7 to 14 consecutive days prior to the first administration of ixabepilone (Day 1). After the lapatinib lead-in phase, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib administered daily, orally once a day, for 21-day cycle.
|
Ixabepilone+ Lapatinib + Capecitabine
A triplet combination of ixabepilone, lapatinib, and capecitabine was planned for analysis in escalating doses but was not initiated due to premature termination of the study.
|
|---|---|---|---|---|
|
Time Period 1: Dose Level 1
Disease progression
|
2
|
0
|
0
|
0
|
|
Time Period 1: Dose Level 1
Physician Decision
|
1
|
0
|
0
|
0
|
|
Time Period 1: Dose Level 1
Adverse Event
|
3
|
0
|
0
|
0
|
|
Time Period 2: Dose Level 2
Adverse Event
|
0
|
2
|
0
|
0
|
|
Time Period 2: Dose Level 2
Progressive disease
|
0
|
1
|
0
|
0
|
|
Time Period 3: Dose Level 3
Progressive disease
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Phase I Study of Ixabepilone Plus Lapatinib With or Without Capecitabine in the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer
Baseline characteristics by cohort
| Measure |
Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg
n=6 Participants
Lapatinib administered daily in escalating cohorts, beginning with 1000 mg, orally once a day, for 7 to 14 consecutive days in Cycle 1 prior to the first administration of ixabepilone. Then lapatinib administered daily, orally once a day, for a 21-day cycle. After the lapatinib lead-in phase, ixabepilone administered as a 3-hour IV infusion in escalating doses, beginning with 32 mg/m\^2.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg
n=3 Participants
Initiated a minimum of 14 days following Day 1 of previous cohort (ixabepilone, 32 mg/m\^2 + lapatinib, 1000 mg), lapatinib 1250 mg administered orally once a day, every day, for 7 to 14 consecutive days prior to the first administration of ixabepilone. Then lapatinib administered orally once a day, every day, for a 21-day cycle. After lapatinib lead-in period, ixabepilone administered as a 3-hour IV infusion of 32 mg/m\^2.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg
n=1 Participants
Initiated a minimum of 14 days following Day 1 of previous cohort (ixabepilone, 32 mg/m\^2 + lapatinib, 1250 mg), lapatinib 1250 mg administered orally once a day, every day for 7 to 14 consecutive days prior to the first administration of ixabepilone in Cycle 1. Then lapatinib administered daily, orally once a day, for a 21-day cycle. Ixabepilone administered as a 3-hour IV infusion of 40 mg/m\^2 following lapatinib lead-in period.
|
Ixabepilone + Lapatinib + Capecitabine
A triplet combination of ixabepilone, lapatinib, and capecitabine was planned for analysis in escalating doses but was not initiated due to premature termination of the study.
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
Younger than 50 years
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
—
|
2 participants
n=21 Participants
|
|
Age, Customized
50 years and older to younger than 65 years
|
4 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
—
|
7 participants
n=21 Participants
|
|
Age, Customized
65 years and older
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
—
|
1 participants
n=21 Participants
|
|
Gender
Female
|
6 participants
n=5 Participants
|
3 participants
n=7 Participants
|
1 participants
n=5 Participants
|
—
|
10 participants
n=21 Participants
|
|
Gender
Male
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
—
|
0 participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
—
|
0 participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
—
|
1 participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
—
|
0 participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
—
|
0 participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
5 participants
n=5 Participants
|
3 participants
n=7 Participants
|
1 participants
n=5 Participants
|
—
|
9 participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
—
|
0 participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
—
|
0 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Days 1 through 21Population: Because the study was terminated due to insufficient enrollment, MTD was not achieved.
The MTD is defined as the maximum dose that can be administered to 6 participants such that no more than 1 (or fewer than one third if more than 6 participants receive treatment) experiences a dose-limiting toxicity (DLT), with at least 2 experiencing a DLT at the next higher dose level. The RP2D is based on the MTD and the assessment of any relevant chronic toxicities.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Days 1 through 21Population: Because the study was terminated due to insufficient enrollment, no participants received the triplet combination.
MTD is defined as the maximum dose that can be administered to 6 participants such that no more than 1 (or fewer than one third if more than 6 participants receive treatment) experiences a DLT, with at least 2 experiencing a DLT at the next higher dose level. The RP2D is based on the MTD and the assessment of any relevant chronic toxicities.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Day 21, continuouslyPopulation: All participants who received at least 1 dose of ixabepilone and either lapatinib or capecitabine.
AE=Any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical event that results in death, persistent or significant disability/incapacity, drug dependency or abuse; is life-threatening, important, a congenital anomaly/birth defect; or requires or prolongs existing hospitalization. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment. Common Terminology Criteria (CTC) Grade 3=severe; Grade 4=life-threatening or disabling.
Outcome measures
| Measure |
All Treated
n=6 Participants
All participants who received at least 1 dose of ixabepilone or lapatinib.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
n=3 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1 and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
n=1 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone + Lapatinib + Capecitabine
Planned escalating doses of ixabepilone, 32 to 40 mg/m\^2 + lapatinib, 1000 to 1250 mg + capecitabine, 1650 to 2000 mg/m\^2. No participants were enrolled in this arm due to premature termination of the study.
|
|---|---|---|---|---|
|
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Treatment-related AEs, Treatment-related AEs (Grade 3 or 4), Peripheral Neuropathy (PN), PN (Grade 3 or 4)
Death
|
3 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Treatment-related AEs, Treatment-related AEs (Grade 3 or 4), Peripheral Neuropathy (PN), PN (Grade 3 or 4)
SAEs
|
2 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Treatment-related AEs, Treatment-related AEs (Grade 3 or 4), Peripheral Neuropathy (PN), PN (Grade 3 or 4)
AEs leading to discontinuation
|
3 Participants
|
2 Participants
|
0 Participants
|
—
|
|
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Treatment-related AEs, Treatment-related AEs (Grade 3 or 4), Peripheral Neuropathy (PN), PN (Grade 3 or 4)
PN
|
4 Participants
|
2 Participants
|
0 Participants
|
—
|
|
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Treatment-related AEs, Treatment-related AEs (Grade 3 or 4), Peripheral Neuropathy (PN), PN (Grade 3 or 4)
Treatment-related AEs
|
6 Participants
|
3 Participants
|
1 Participants
|
—
|
|
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Treatment-related AEs, Treatment-related AEs (Grade 3 or 4), Peripheral Neuropathy (PN), PN (Grade 3 or 4)
Treatment-related AEs (Grade 3 or 4)
|
3 Participants
|
3 Participants
|
1 Participants
|
—
|
|
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Treatment-related AEs, Treatment-related AEs (Grade 3 or 4), Peripheral Neuropathy (PN), PN (Grade 3 or 4)
PN (Grade 3 or 4)
|
1 Participants
|
1 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline to Day 21, continuouslyPopulation: All participants who received at least 1 dose of ixabepilone and either lapatinib or capecitabine.
DLT=Any of the following events, attributable to study drug and occurring within 21 days after ixabepilone administration: Grade 3 or 4 nausea, vomiting, or diarrhea despite the use of adequate medical intervention; other Grade 3 or greater nonhematologic toxicity requiring removal from study drug; recovery from study drug-related toxicity that delayed scheduled retreatment for longer than 3 weeks; Grade 4 neutropenia for 5 or more consecutive days or Grade 3 or 4 neutropenia of any duration with sepsis or fever; thrombocytopenia or bleeding requiring platelet transfusion.
Outcome measures
| Measure |
All Treated
n=6 Participants
All participants who received at least 1 dose of ixabepilone or lapatinib.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
n=3 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1 and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
n=1 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone + Lapatinib + Capecitabine
Planned escalating doses of ixabepilone, 32 to 40 mg/m\^2 + lapatinib, 1000 to 1250 mg + capecitabine, 1650 to 2000 mg/m\^2. No participants were enrolled in this arm due to premature termination of the study.
|
|---|---|---|---|---|
|
Number of Participants With DLT
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline and weekly from Days 1 to 21 (Cycle 1)Population: All participants who received at least 1 dose of ixabepilone and either lapatinib or capecitabine.
CTC, Version 3.0 used to assess parameters. ULN=upper level of normal among all laboratory ranges. WBC (c/L): 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 (c/uL): 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 (c/uL): 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\*10\^9/L; Hemoglobin (g/dL): 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.
Outcome measures
| Measure |
All Treated
n=6 Participants
All participants who received at least 1 dose of ixabepilone or lapatinib.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
n=3 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1 and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
n=1 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone + Lapatinib + Capecitabine
Planned escalating doses of ixabepilone, 32 to 40 mg/m\^2 + lapatinib, 1000 to 1250 mg + capecitabine, 1650 to 2000 mg/m\^2. No participants were enrolled in this arm due to premature termination of the study.
|
|---|---|---|---|---|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
WBC (Grade 2)
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
Absolute neutrophil count (ANC) (Grade 1)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
Platelet count (Grade 1)
|
1 Participants
|
1 Participants
|
2 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
Platelet count (Grade 2)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
White blood cell count (WBC) (Grade 1)
|
1 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
WBC (Grade 3)
|
2 Participants
|
3 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
WBC (Grade 4)
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
ANC (Grade 2)
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
ANC (Grade 3)
|
2 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
ANC (Grade 4)
|
2 Participants
|
2 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
Platelet count (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
Platelet count (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
Hemoglobin (Grade 1)
|
3 Participants
|
3 Participants
|
6 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
Hemoglobin (Grade 2)
|
3 Participants
|
0 Participants
|
4 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
Hemoglobin (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst CTC Grade
Hemoglobin (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: At baseline and within 72 hours of Day 1 of 21-day cyclePopulation: All participants who received at least 1 dose of ixabepilone and either lapatinib or capecitabine.
CTC, Version 3.0 used to assess parameters. ULN=upper level of normal among all laboratory ranges. ALT(U/L) Gr 1:\>ULN-2.5\*ULN,Gr 2:\>2.5-5.0\*ULN,Gr 3:\>5.0-20.0\*ULN,Gr 4:\>20.0\* ULN; AST(U/L) Gr 1:\>ULN-2.5\* ULN,Gr 2:\>2.5-5.0\*ULN,Gr 3:\>5.0-20.0\*ULN,Gr 4:\>20.0\* ULN; ALP(U/L)Gr 1:\>ULN-2.5\*ULN, Gr 2:\>2.5-5.0\*ULN, Gr 3:\>5.0-20.0\*ULN, Gr 4:\>20.0\*ULN; Creatinine (mg/dL): Gr 1:\>ULN-1.5\*ULN, Gr 2:\>1.5-3.0\*ULN, Gr 3:\>3.0-6.0\*ULN, Gr 4:\>6.0\*ULN; Total bilirubin (mg/dL): Gr 1:\>ULN-1.5\*ULN, Gr 2:\>1.5-3.0\*ULN, Gr 3:\>3.0-10.0\*ULN, Gr 4:\>10.0\*ULN
Outcome measures
| Measure |
All Treated
n=6 Participants
All participants who received at least 1 dose of ixabepilone or lapatinib.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
n=3 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1 and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
n=1 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone + Lapatinib + Capecitabine
Planned escalating doses of ixabepilone, 32 to 40 mg/m\^2 + lapatinib, 1000 to 1250 mg + capecitabine, 1650 to 2000 mg/m\^2. No participants were enrolled in this arm due to premature termination of the study.
|
|---|---|---|---|---|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
ALT (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
Alkaline phosphatase (ALP) (Grade 1)
|
3 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
Creatinine (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
Total bilirubin (Grade 1)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
Total bilirubin (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
Alanine aminotransferase (ALT) (Grade 1)
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
ALT (Grade 2)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
ALT (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
Aspartate aminotransferase (AST) (Grade 1)
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
AST (Grade 2)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
AST (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
AST (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
ALP (Grade 2)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
ALP (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
ALP (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
Creatinine (Grade 1)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
Creatinine (Grade 2)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
Creatinine (Grade 3)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
Total bilirubin (Grade 2)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results by Worst CTC Grade
Total bilirubin (Grade 4)
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Day 1 of 21-day cyclePopulation: Participants who received ixabepilone with lapatinib treatment and had pharmacokinetic parameters available.
Outcome measures
| Measure |
All Treated
n=5 Participants
All participants who received at least 1 dose of ixabepilone or lapatinib.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
n=3 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1 and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
n=1 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone + Lapatinib + Capecitabine
Planned escalating doses of ixabepilone, 32 to 40 mg/m\^2 + lapatinib, 1000 to 1250 mg + capecitabine, 1650 to 2000 mg/m\^2. No participants were enrolled in this arm due to premature termination of the study.
|
|---|---|---|---|---|
|
Maximum Concentration of Ixabepilone
|
200.6 ng/mL
Standard Deviation 78.4 • Interval 105.5 to 311.1
|
109.2 ng/mL
Standard Deviation 1.1 • Interval 107.9 to 110.1
|
133.4 ng/mL
Interval 133.4 to 133.4
|
—
|
SECONDARY outcome
Timeframe: Day 1 of 21-day cyclePopulation: Participants who received ixabepilone with lapatinib treatment and had pharmacokinetic parameters available.
Outcome measures
| Measure |
All Treated
n=5 Participants
All participants who received at least 1 dose of ixabepilone or lapatinib.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
n=3 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1 and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
n=1 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone + Lapatinib + Capecitabine
Planned escalating doses of ixabepilone, 32 to 40 mg/m\^2 + lapatinib, 1000 to 1250 mg + capecitabine, 1650 to 2000 mg/m\^2. No participants were enrolled in this arm due to premature termination of the study.
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve From 0 to Infinity (AUC[INF]) and AUC From 0 to Last Quantifiable Concentration (AUC[O-T] of Ixabepilone
AUC(INF)
|
2212.9 ng*h/mL
Standard Deviation 1030.4
|
2427.0 ng*h/mL
Standard Deviation 225.5
|
1610.7 ng*h/mL
|
—
|
|
Area Under the Concentration-time Curve From 0 to Infinity (AUC[INF]) and AUC From 0 to Last Quantifiable Concentration (AUC[O-T] of Ixabepilone
AUC(O-T)
|
1851.8 ng*h/mL
Standard Deviation 880.5
|
2082.0 ng*h/mL
Standard Deviation 133.6
|
1284.2 ng*h/mL
|
—
|
SECONDARY outcome
Timeframe: Day 1 of 21-day cyclePopulation: Participants who received ixabepilone with lapatinib treatment and had pharmacokinetic parameters available.
Outcome measures
| Measure |
All Treated
n=5 Participants
All participants who received at least 1 dose of ixabepilone or lapatinib.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
n=3 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1 and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
n=1 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone + Lapatinib + Capecitabine
Planned escalating doses of ixabepilone, 32 to 40 mg/m\^2 + lapatinib, 1000 to 1250 mg + capecitabine, 1650 to 2000 mg/m\^2. No participants were enrolled in this arm due to premature termination of the study.
|
|---|---|---|---|---|
|
Terminal Half-life of Ixabepilone
|
51.6 Hours
Standard Deviation 13.2
|
63.1 Hours
Standard Deviation 10.4
|
33.1 Hours
|
—
|
SECONDARY outcome
Timeframe: Day 1 of 21-day cyclePopulation: Participants who received ixabepilone with lapatinib treatment and had pharmacokinetic parameters available.
Outcome measures
| Measure |
All Treated
n=5 Participants
All participants who received at least 1 dose of ixabepilone or lapatinib.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
n=3 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1 and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
n=1 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone + Lapatinib + Capecitabine
Planned escalating doses of ixabepilone, 32 to 40 mg/m\^2 + lapatinib, 1000 to 1250 mg + capecitabine, 1650 to 2000 mg/m\^2. No participants were enrolled in this arm due to premature termination of the study.
|
|---|---|---|---|---|
|
Time to Peak Concentration of Ixabepilone
|
3.0 Hours
Interval 2.0 to 3.4
|
3.0 Hours
Interval 3.0 to 3.0
|
2.9 Hours
Interval 2.9 to 2.9
|
—
|
SECONDARY outcome
Timeframe: Day 1 of 21-day cyclePopulation: Participants who received ixabepilone with lapatinib treatment and had pharmacokinetic parameters available.
Outcome measures
| Measure |
All Treated
n=5 Participants
All participants who received at least 1 dose of ixabepilone or lapatinib.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
n=3 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1 and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
n=1 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone + Lapatinib + Capecitabine
Planned escalating doses of ixabepilone, 32 to 40 mg/m\^2 + lapatinib, 1000 to 1250 mg + capecitabine, 1650 to 2000 mg/m\^2. No participants were enrolled in this arm due to premature termination of the study.
|
|---|---|---|---|---|
|
Volume of Distribution at Steady State of Ixabepilone
|
1484.3 Liters
Standard Deviation 438.5
|
1780.8 Liters
Standard Deviation 237.9
|
1915.8 Liters
|
—
|
SECONDARY outcome
Timeframe: Baseline and Day 21 (21-day cycle)Population: All participants with measurable disease at baseline per RECIST guidelines, with the exception of those with an incorrect diagnosis.
Target lesion criteria: Complete Response(CR)=Disappearance of all clinical and radiologic evidence of target lesions; Partial Response (PR)=A 30% or greater decrease in the sum of longest diameter(LD) of all lesions in reference to the baseline sum LD. Stable Disease (SD)=Insufficient increase to qualify for Progressive Disease (PD) and insufficient shrinkage to qualify for PR; PD=A 20% or greater increase in the sum of LD of all target lesions, taking as reference the smallest sum LD recorded at or following baseline.
Outcome measures
| Measure |
All Treated
n=6 Participants
All participants who received at least 1 dose of ixabepilone or lapatinib.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
n=3 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1 and on Day 1 of subsequent cycles, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
n=1 Participants
Lapatinib, 1250 mg, administered daily, orally once a day, at least 1 hour before or after a meal, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase of Cycle 1, and on Day 1 of subsequent cycles, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for a 21-day cycle.
|
Ixabepilone + Lapatinib + Capecitabine
Planned escalating doses of ixabepilone, 32 to 40 mg/m\^2 + lapatinib, 1000 to 1250 mg + capecitabine, 1650 to 2000 mg/m\^2. No participants were enrolled in this arm due to premature termination of the study.
|
|---|---|---|---|---|
|
Overall Tumor Response By Number of Participants
CR
|
3 Participants
12.2
|
2 Participants
2.1
|
0 Participants
|
—
|
|
Overall Tumor Response By Number of Participants
PR
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Overall Tumor Response By Number of Participants
SD
|
3 Participants
|
1 Participants
|
1 Participants
|
—
|
|
Overall Tumor Response By Number of Participants
PD
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: First occurrence of PR or CR to PD or Death (no average, as no data available)Population: Because the study was terminated due to insufficient enrollment, the duration of response could not be analyzed.
Duration of response is measured from the time in months that measurement criteria are first met for PR or CR, whichever is recorded first, until the date of documented PD or death. Participants who neither relapse nor die will be censored on the date of their last tumor assessment.
Outcome measures
Outcome data not reported
Adverse Events
Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg/d
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg/d
n=6 participants at risk
Lapatinib, 1000 mg, administered daily in a lead-in period, orally once a day, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1000 mg, administered daily, orally once a day, for 21-day cycle.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
n=3 participants at risk
Lapatinib, 1250 mg, administered daily in a lead-in period, orally once a day, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
n=1 participants at risk
Lapatinib, 1250 mg, administered daily in a lead-in period, orally once a day, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for 21-day cycle.
|
|---|---|---|---|
|
Gastrointestinal disorders
NAUSEA
|
0.00%
0/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
VOMITING
|
0.00%
0/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Infections and infestations
DEVICE RELATED INFECTION
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.00%
0/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Blood and lymphatic system disorders
ANAEMIA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
General disorders
FATIGUE
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
General disorders
CHEST PAIN
|
0.00%
0/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
Other adverse events
| Measure |
Ixabepilone, 32 mg/m^2 + Lapatinib, 1000 mg/d
n=6 participants at risk
Lapatinib, 1000 mg, administered daily in a lead-in period, orally once a day, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1000 mg, administered daily, orally once a day, for 21-day cycle.
|
Ixabepilone, 32 mg/m^2 + Lapatinib, 1250 mg/d
n=3 participants at risk
Lapatinib, 1250 mg, administered daily in a lead-in period, orally once a day, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase, ixabepilone, 32 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for 21-day cycle.
|
Ixabepilone, 40 mg/m^2 + Lapatinib, 1250 mg/d
n=1 participants at risk
Lapatinib, 1250 mg, administered daily in a lead-in period, orally once a day, for 7 to 14 consecutive days prior to first administration of ixabepilone (Day 1). After the lapatinib lead-in phase, ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion. Lapatinib, 1250 mg, administered daily, orally once a day, for 21-day cycle.
|
|---|---|---|---|
|
Eye disorders
CATARACT
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Eye disorders
CYCLOPLEGIA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Eye disorders
VISION BLURRED
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Eye disorders
VISUAL ACUITY REDUCED
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Eye disorders
NEUROLOGICAL EYELID DISORDER
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Investigations
WEIGHT DECREASED
|
0.00%
0/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Investigations
HAEMOGLOBIN DECREASED
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Investigations
BLOOD MAGNESIUM DECREASED
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Investigations
BLOOD POTASSIUM DECREASED
|
33.3%
2/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Investigations
EJECTION FRACTION DECREASED
|
0.00%
0/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
0.00%
0/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Cardiac disorders
PALPITATIONS
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Vascular disorders
FLUSHING
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Vascular disorders
LYMPHOEDEMA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Vascular disorders
HYPERTENSION
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Vascular disorders
ORTHOSTATIC HYPOTENSION
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Psychiatric disorders
INSOMNIA
|
33.3%
2/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Psychiatric disorders
DEPRESSION
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Hepatobiliary disorders
PORTAL VEIN THROMBOSIS
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Immune system disorders
DRUG HYPERSENSITIVITY
|
33.3%
2/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Nervous system disorders
AGEUSIA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Nervous system disorders
HEADACHE
|
33.3%
2/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Nervous system disorders
LETHARGY
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Nervous system disorders
DYSGEUSIA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Nervous system disorders
NEURALGIA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Nervous system disorders
PARAESTHESIA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Nervous system disorders
PERIPHERAL SENSORY NEUROPATHY
|
66.7%
4/6 • Baseline to Day 21, continuously
|
66.7%
2/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
NAUSEA
|
83.3%
5/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
VOMITING
|
50.0%
3/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
DIARRHOEA
|
83.3%
5/6 • Baseline to Day 21, continuously
|
100.0%
3/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
GASTRITIS
|
0.00%
0/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
CONSTIPATION
|
33.3%
2/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
MOUTH ULCERATION
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
PARAESTHESIA ORAL
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
HYPOAESTHESIA ORAL
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
FAECAL INCONTINENCE
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Infections and infestations
BRONCHITIS
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Infections and infestations
CELLULITIS
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Infections and infestations
FOLLICULITIS
|
0.00%
0/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Infections and infestations
NASOPHARYNGITIS
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Infections and infestations
LOCALISED INFECTION
|
33.3%
2/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Infections and infestations
DEVICE RELATED INFECTION
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
33.3%
2/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Renal and urinary disorders
POLLAKIURIA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Renal and urinary disorders
MICTURITION URGENCY
|
0.00%
0/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.00%
0/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
0.00%
0/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
33.3%
2/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Blood and lymphatic system disorders
ANAEMIA
|
33.3%
2/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
0.00%
0/6 • Baseline to Day 21, continuously
|
66.7%
2/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
50.0%
3/6 • Baseline to Day 21, continuously
|
100.0%
3/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Skin and subcutaneous tissue disorders
RASH
|
16.7%
1/6 • Baseline to Day 21, continuously
|
66.7%
2/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Skin and subcutaneous tissue disorders
ONYCHOLYSIS
|
0.00%
0/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Skin and subcutaneous tissue disorders
PAIN OF SKIN
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Skin and subcutaneous tissue disorders
RASH MACULAR
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Skin and subcutaneous tissue disorders
NAIL DISORDER
|
33.3%
2/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Skin and subcutaneous tissue disorders
HYPOAESTHESIA FACIAL
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Injury, poisoning and procedural complications
FALL
|
33.3%
2/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
50.0%
3/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
66.7%
4/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
33.3%
2/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
0.00%
0/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
33.3%
2/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
16.7%
1/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
0.00%
0/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
33.3%
2/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
General disorders
PAIN
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
General disorders
FATIGUE
|
66.7%
4/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
General disorders
PYREXIA
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
General disorders
EXTRAVASATION
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
General disorders
CHEST DISCOMFORT
|
16.7%
1/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
|
General disorders
OEDEMA PERIPHERAL
|
50.0%
3/6 • Baseline to Day 21, continuously
|
0.00%
0/3 • Baseline to Day 21, continuously
|
100.0%
1/1 • Baseline to Day 21, continuously
|
|
General disorders
MUCOSAL INFLAMMATION
|
16.7%
1/6 • Baseline to Day 21, continuously
|
33.3%
1/3 • Baseline to Day 21, continuously
|
0.00%
0/1 • Baseline to Day 21, continuously
|
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 of 60 days or less 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