Trial Outcomes & Findings for Phase 1 Trial of Oral Ixabepilone (NCT NCT00632424)
NCT ID: NCT00632424
Last Updated: 2016-03-10
Results Overview
DLT: any of the following, considered related to ixabepilone, occurring in Cycle 1: Absolute neutrophil count (ANC) \<500 cells/mm\^3 for ≥5 consecutive days or febrile neutropenia of any duration; Grade(Gr)4 thrombocytopenia \<25,000 cells/mm\^3 or Gr3 with bleeding requiring platelet transfusion; Gr3/4 nausea, vomiting, or diarrhea despite use of adequate intervention, fatigue, any other clinically significant drug-related ≥Gr 3 non-hematologic toxicity, delayed recovery (to Gr ≤1 or baseline, except alopecia) from toxicity which delays initiation of Cycle 2 by ≥3 weeks.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
23 participants
Primary outcome timeframe
During Cycle 1 (Day 0 through Day 21)
Results posted on
2016-03-10
Participant Flow
23 participants enrolled in this study; five participants were never treated due to not meeting study criteria (n=4) and withdrawal of consent (n=1).
Participant milestones
| Measure |
All Treated Participants
Ixabepilone was given as 3 oral doses separated by 6 hours at 30 mg, 40 mg, or 50 mg doses every 6 hours for 3 total doses on Day 1 of a 21-day cycle.
|
|---|---|
|
Overall Study
STARTED
|
18
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
18
|
Reasons for withdrawal
| Measure |
All Treated Participants
Ixabepilone was given as 3 oral doses separated by 6 hours at 30 mg, 40 mg, or 50 mg doses every 6 hours for 3 total doses on Day 1 of a 21-day cycle.
|
|---|---|
|
Overall Study
Disease Progression
|
17
|
|
Overall Study
Study Drug Toxicity
|
1
|
Baseline Characteristics
Phase 1 Trial of Oral Ixabepilone
Baseline characteristics by cohort
| Measure |
Ixabepilone 90 mg/Day
n=3 Participants
The starting dose level was 30 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (30 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 90 mg per cycle.
|
Ixabepilone 120 mg/Day
n=9 Participants
Participants received 40 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (40 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 120 mg per cycle.
|
Ixabepilone 150 mg/Day
n=6 Participants
Participants received 50 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (50 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 150 mg per cycle.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
59.0 years
n=5 Participants
|
69.0 years
n=7 Participants
|
56.0 years
n=5 Participants
|
59.0 years
n=4 Participants
|
|
Age, Customized
Greater than, equal to 65 years
|
1 participants
n=5 Participants
|
5 participants
n=7 Participants
|
0 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Age, Customized
Less than 65 years
|
2 participants
n=5 Participants
|
4 participants
n=7 Participants
|
6 participants
n=5 Participants
|
12 participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: During Cycle 1 (Day 0 through Day 21)Population: All participants who received at least one dose of ixabepilone.
DLT: any of the following, considered related to ixabepilone, occurring in Cycle 1: Absolute neutrophil count (ANC) \<500 cells/mm\^3 for ≥5 consecutive days or febrile neutropenia of any duration; Grade(Gr)4 thrombocytopenia \<25,000 cells/mm\^3 or Gr3 with bleeding requiring platelet transfusion; Gr3/4 nausea, vomiting, or diarrhea despite use of adequate intervention, fatigue, any other clinically significant drug-related ≥Gr 3 non-hematologic toxicity, delayed recovery (to Gr ≤1 or baseline, except alopecia) from toxicity which delays initiation of Cycle 2 by ≥3 weeks.
Outcome measures
| Measure |
Ixabepilone 90 mg/Day
n=3 Participants
The starting dose level was 30 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (30 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 90 mg per cycle.
|
Ixabepilone 120 mg/Day
n=9 Participants
Participants received 40 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (40 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 120 mg per cycle.
|
Ixabepilone 150 mg/Day
n=6 Participants
Participants received 50 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (50 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 150 mg per cycle.
|
|---|---|---|---|
|
Number of Participants With a Dose-Limiting Toxicity (DLT)
ANC <500 cells/mm^3 for ≥5 consecutive days
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Dose-Limiting Toxicity (DLT)
Grade 4 febrile neutropenia
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With a Dose-Limiting Toxicity (DLT)
Grade 4 neutropenic sepsis
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With a Dose-Limiting Toxicity (DLT)
Grade 4 thrombocytopenia <25000 cells/mm^3
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Dose-Limiting Toxicity (DLT)
Grade 3 thrombocytopenia with bleeding episode
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Dose-Limiting Toxicity (DLT)
Grade 3/4 nausea
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Dose-Limiting Toxicity (DLT)
Grade 3/4 vomiting
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Dose-Limiting Toxicity (DLT)
Grade 3/4 diarrhea
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Dose-Limiting Toxicity (DLT)
Fatigue
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Dose-Limiting Toxicity (DLT)
Drug-related ≥3 non-hematologic toxicity
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With a Dose-Limiting Toxicity (DLT)
Delayed recovery from drug-related toxicity
|
0 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: At the end of Cycle 1 (21 days).Population: Due to early study discontinuation, the MTD and RP2D of oral ixabepilone at the scheduled doses used in this study were not determined
The MTD was defined as the maximum dose which could be given to 6 participants such that not more than 1 participant experienced a DLT (or fewer than one-third if there were more than 6 treated participants) with at least 2 participants experiencing a DLT at the next higher dose level. The R2PD was to be based on the MTD and the assessment of any relevant chronic toxicities.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From first study drug administration through 30 days post dosePopulation: All participants who received at least one dose of ixabepilone.
AEs graded according to Common Terminology Criteria Version 3.0 (CTC v 3.0). AE=any new untoward medical occurrence or worsening of a pre-existing medical condition not necessarily having a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization/causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, or is an important medical event.
Outcome measures
| Measure |
Ixabepilone 90 mg/Day
n=18 Participants
The starting dose level was 30 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (30 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 90 mg per cycle.
|
Ixabepilone 120 mg/Day
Participants received 40 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (40 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 120 mg per cycle.
|
Ixabepilone 150 mg/Day
Participants received 50 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (50 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 150 mg per cycle.
|
|---|---|---|---|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Grade (Gr) 1 (mild) AE
|
2 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 2 (moderate) AE
|
7 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 3 (severe) AE
|
5 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 4 (life-threatening, [LT]) AE
|
2 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 5 (death) AE
|
1 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
All AEs
|
17 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 4 (LT) AE Leading to Discontinuation (DC)
|
1 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
All AEs Leading to DC
|
1 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 1 (mild) Treatment-related AE
|
7 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 2 (moderate) Treatment-related AE
|
5 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 3 (severe) Treatment-related AE
|
2 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 4 (LT) Treatment-related AE
|
2 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
All Treatment-related AEs
|
16 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 3 (severe) SAE
|
2 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 4 (LT) SAE
|
2 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 5 (death) SAE
|
1 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
All SAEs
|
5 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
Gr 4 (LT) Treatment-related SAE
|
2 participants
|
—
|
—
|
|
Number of Participants With Adverse Event (AE), AE Leading to Discontinuation, Treatment-related AE, Treatment-related AE Leading to Discontinuation (DC), Most Common Treatment-Related Nonhematologic AE (>25%), Serious AE (SAE), or Treatment-related SAE
All Treatment-related SAE
|
2 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From first study drug administration through 30 days post dosePopulation: All participants who received at least one dose of ixabepilone.
AEs graded according to Common Terminology Criteria Version 3.0 (CTC v 3.0). AE=any new untoward medical occurrence or worsening of a pre-existing medical condition not necessarily having a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization/causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, or is an important medical event.
Outcome measures
| Measure |
Ixabepilone 90 mg/Day
n=18 Participants
The starting dose level was 30 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (30 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 90 mg per cycle.
|
Ixabepilone 120 mg/Day
Participants received 40 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (40 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 120 mg per cycle.
|
Ixabepilone 150 mg/Day
Participants received 50 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (50 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 150 mg per cycle.
|
|---|---|---|---|
|
Number of Participants With Most Common Treatment-Related Nonhematologic AEs (>25%)
Gr 1 (mild) Fatigue
|
4 participants
|
—
|
—
|
|
Number of Participants With Most Common Treatment-Related Nonhematologic AEs (>25%)
Gr 2 (moderate) Fatigue
|
3 participants
|
—
|
—
|
|
Number of Participants With Most Common Treatment-Related Nonhematologic AEs (>25%)
Gr 4 (LT) Fatigue
|
1 participants
|
—
|
—
|
|
Number of Participants With Most Common Treatment-Related Nonhematologic AEs (>25%)
All Fatigue
|
8 participants
|
—
|
—
|
|
Number of Participants With Most Common Treatment-Related Nonhematologic AEs (>25%)
Gr 1 (mild) Nausea
|
7 participants
|
—
|
—
|
|
Number of Participants With Most Common Treatment-Related Nonhematologic AEs (>25%)
All Nausea
|
7 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From first study drug administration through 30 days post dosePopulation: All participants who received at least one dose of ixabepilone.
Laboratory results were graded according to CTC v 3.0. Hematology laboratory evaluations included absolute neutrophil count (ANC), white blood cell count (WBC), platelets (PLT), and hemoglobin (HGB).
Outcome measures
| Measure |
Ixabepilone 90 mg/Day
n=18 Participants
The starting dose level was 30 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (30 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 90 mg per cycle.
|
Ixabepilone 120 mg/Day
Participants received 40 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (40 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 120 mg per cycle.
|
Ixabepilone 150 mg/Day
Participants received 50 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (50 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 150 mg per cycle.
|
|---|---|---|---|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 0 (no abnormality) WBC
|
4 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 1 (mild) WBC
|
5 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 2 (moderate) WBC
|
5 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 3 (severe) WBC
|
1 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 4 (LT) WBC
|
3 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 0 (no abnormality) ANC
|
8 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 1 ANC
|
3 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 2 (moderate) ANC
|
2 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 3 (severe) ANC
|
3 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 4 (LT) ANC
|
2 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 0 (no abnormality) PLT
|
14 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 1 (mild) PLT
|
3 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 4 (LT) PLT
|
1 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 1 (mild) HGB
|
10 participants
|
—
|
—
|
|
Number of Participants With Hematology Laboratory Abnormalities
Gr 2 (moderate) HGB
|
8 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From first study drug administration through 30 days post dosePopulation: Since study NCT00632424 (CA163-149) was discontinued early due to variability in oral ixabepilone concentrations with the potential to negatively impact both safety and efficacy, liver and renal laboratory data were collected but not summarized.
Laboratory results were graded according to CTC v 3.0. Clinical laboratory evaluations included liver function (alanine aminotransferase \[ALT\], Aspartate aminotransferase \[AST\], alkaline phosphatase, and total bilirubin), and renal function (creatinine).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 1Population: Since study NCT00632424 (CA163-149) was discontinued early due to variability in oral ixabepilone concentrations with the potential to negatively impact both safety and efficacy, QTc data were collected but not analyzed.
QTc interval was defined as the measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, corrected for heart rate
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 12.5, 13, 14, 15, 16, 17, 18, 20, 48, 72, and 168 hours post dosePopulation: Number of Participants Analyzed =All participants who received any treatment with ixabepilone and had adequate concentration profiles, n=all participants who received ixabepilone and had adequate concentration profiles at the specified time point. Cmax, Cmin, Tmax, AUC (0-TAU), and T-half were not calculated.
Pharmacokinetics (PK) of ixabepilone were derived from plasma concentration versus time data. Individual patient PK parameter values were derived by standard non-compartmental methods by a validated pharmacokinetic analysis program. PK parameters include Cmax (maximum plasma concentration), Cmin (minimum plasma concentration), Tmax (time of maximum plasma concentration), AUC (0-TAU) (area under the curve in one dosing interval), T-half (plasma half-life).
Outcome measures
| Measure |
Ixabepilone 90 mg/Day
n=3 Participants
The starting dose level was 30 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (30 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 90 mg per cycle.
|
Ixabepilone 120 mg/Day
n=9 Participants
Participants received 40 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (40 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 120 mg per cycle.
|
Ixabepilone 150 mg/Day
n=6 Participants
Participants received 50 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (50 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 150 mg per cycle.
|
|---|---|---|---|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 0 hours (hrs)
|
0 ng/ml
Standard Deviation 0
|
0 ng/ml
Standard Deviation 0
|
0 ng/ml
Standard Deviation 0
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 0.5 hrs (n=1, n=1, n=1)
|
2.77 ng/ml
Standard Deviation 0
|
11.46 ng/ml
Standard Deviation 0
|
7.86 ng/ml
Standard Deviation 0
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 1 hrs (n=1, n=5, n=4)
|
9.31 ng/ml
Standard Deviation 0
|
19.93 ng/ml
Standard Deviation 21.3
|
41.82 ng/ml
Standard Deviation 52.44
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 2 hrs (n=2, n=6, n=n=6)
|
29.67 ng/ml
Standard Deviation 29.49
|
73.57 ng/ml
Standard Deviation 81.25
|
104.91 ng/ml
Standard Deviation 52.99
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 3 hrs (n=3, n=8, n=6)
|
52.75 ng/ml
Standard Deviation 54.89
|
56.2 ng/ml
Standard Deviation 33.30
|
124.51 ng/ml
Standard Deviation 66.16
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 4 hrs (n=3, n=8, , n=6)
|
24.18 ng/ml
Standard Deviation 13.62
|
30.23 ng/ml
Standard Deviation 21.80
|
52.16 ng/ml
Standard Deviation 31.23
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 5 hrs (n=3, n=8, n=6)
|
16.64 ng/ml
Standard Deviation 9.66
|
22.24 ng/ml
Standard Deviation 18.62
|
36.54 ng/ml
Standard Deviation 21.13
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 6 hrs (n=3, n=8, n=6)
|
12.84 ng/ml
Standard Deviation 7.81
|
17.75 ng/ml
Standard Deviation 15.92
|
32.08 ng/ml
Standard Deviation 20.15
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 8 hrs (n=3, n=8, n=6)
|
11.19 ng/ml
Standard Deviation 3.87
|
32.50 ng/ml
Standard Deviation 33.33
|
104.54 ng/ml
Standard Deviation 122.82
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 12 hrs (n=3, n=9, n=6)
|
26.76 ng/ml
Standard Deviation 35.20
|
24.84 ng/ml
Standard Deviation 38.33
|
49.41 ng/ml
Standard Deviation 26.57
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 12.5 hrs (n=3, n=9, n=6)
|
24.24 ng/ml
Standard Deviation 30.31
|
22.58 ng/ml
Standard Deviation 35.24
|
78.35 ng/ml
Standard Deviation 102.94
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 13 hrs (n=3, n=9, n=6)
|
17.63 ng/ml
Standard Deviation 20.47
|
25.94 ng/ml
Standard Deviation 30.20
|
103.24 ng/ml
Standard Deviation 166.47
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 14 hrs (n=3, n=9, n=6)
|
19.6 ng/ml
Standard Deviation 24.98
|
52.17 ng/ml
Standard Deviation 51.73
|
59.02 ng/ml
Standard Deviation 74.01
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 15 hrs (n=3, n=9, n=6)
|
18.52 ng/ml
Standard Deviation 23.07
|
39.52 ng/ml
Standard Deviation 29.80
|
86.30 ng/ml
Standard Deviation 134.08
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 16 hrs (n=3, n=9, n=6)
|
27.37 ng/ml
Standard Deviation 23.34
|
43.62 ng/ml
Standard Deviation 37.63
|
93.53 ng/ml
Standard Deviation 144.91
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 17 hrs (n=3, n=9, n=6)
|
76.63 ng/ml
Standard Deviation 79.12
|
37.31 ng/ml
Standard Deviation 33.27
|
116.04 ng/ml
Standard Deviation 196.12
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 18 hrs (n=3, n=9, n=6)
|
38.32 ng/ml
Standard Deviation 27.42
|
41.13 ng/ml
Standard Deviation 45.41
|
94.27 ng/ml
Standard Deviation 142.91
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 20 hrs (n=3, n=9, n=6)
|
24.71 ng/ml
Standard Deviation 17.20
|
43.04 ng/ml
Standard Deviation 38.39
|
89.71 ng/ml
Standard Deviation 78.41
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 48 hrs (n=2, n=9, n=4)
|
11.77 ng/ml
Standard Deviation 4.16
|
13.60 ng/ml
Standard Deviation 17.77
|
24.41 ng/ml
Standard Deviation 15.33
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 72 hrs (n=2, n=8, n=4)
|
7.20 ng/ml
Standard Deviation 2.05
|
10.49 ng/ml
Standard Deviation 12.68
|
14.81 ng/ml
Standard Deviation 9.62
|
|
PK: Mean Plasma Concentration Of Ixabepilone By Nominal Collection Time
Time 168 hrs (n=1, n=4, n=n=4)
|
3.12 ng/ml
Standard Deviation 0.00
|
7.80 ng/ml
Standard Deviation 7.84
|
6.28 ng/ml
Standard Deviation 5.90
|
SECONDARY outcome
Timeframe: Tumor assessments performed on Day 1 of every other cycle of therapy, until disease progression or toxicityPopulation: All treated participants who received at least one dose of ixabepilone were evaluable for tumor response.
Tumor assessment was performed according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR) = disappearance of all clinical and radiological evidence of target lesions; Partial Response (PR) = at least 30% reduction in the sum of the longest diameter of all target lesions; Progressive disease (PD) = at least 20% increase in the sum of the longest diameter of all target lesions; Stable Disease (SD) = neither PR nor PD criteria were met.
Outcome measures
| Measure |
Ixabepilone 90 mg/Day
n=3 Participants
The starting dose level was 30 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (30 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 90 mg per cycle.
|
Ixabepilone 120 mg/Day
n=9 Participants
Participants received 40 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (40 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 120 mg per cycle.
|
Ixabepilone 150 mg/Day
n=6 Participants
Participants received 50 mg/dose for ixabepilone given as 3 oral doses separated by 6 hours (50 mg every 6 hours for 3 doses) on Day 1 of a 21-day cycle for a total dose of 150 mg per cycle.
|
|---|---|---|---|
|
Best Overall Response
Stable Disease
|
1 participants
|
2 participants
|
2 participants
|
|
Best Overall Response
Complete Response
|
0 participants
|
0 participants
|
0 participants
|
|
Best Overall Response
Partial Response
|
0 participants
|
0 participants
|
0 participants
|
|
Best Overall Response
Progressive Disease
|
2 participants
|
7 participants
|
3 participants
|
|
Best Overall Response
Unable To Be Determined
|
0 participants
|
0 participants
|
1 participants
|
Adverse Events
Ixa 90 mg/Day
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Ixa 120 mg/Day
Serious events: 2 serious events
Other events: 8 other events
Deaths: 0 deaths
Ixa 150 mg/Day
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ixa 90 mg/Day
n=3 participants at risk
|
Ixa 120 mg/Day
n=9 participants at risk
|
Ixa 150 mg/Day
n=6 participants at risk
|
|---|---|---|---|
|
Gastrointestinal disorders
DYSPHAGIA
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Infections and infestations
ABDOMINAL ABSCESS
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Infections and infestations
NEUTROPENIC SEPSIS
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.00%
0/3
|
11.1%
1/9
|
16.7%
1/6
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
0.00%
0/3
|
11.1%
1/9
|
16.7%
1/6
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONIA ASPIRATION
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
General disorders
FATIGUE
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
General disorders
CHEST PAIN
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
General disorders
MUCOSAL INFLAMMATION
|
0.00%
0/3
|
11.1%
1/9
|
16.7%
1/6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT NEOPLASM PROGRESSION
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
Other adverse events
| Measure |
Ixa 90 mg/Day
n=3 participants at risk
|
Ixa 120 mg/Day
n=9 participants at risk
|
Ixa 150 mg/Day
n=6 participants at risk
|
|---|---|---|---|
|
Gastrointestinal disorders
ABDOMINAL PAIN LOWER
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Infections and infestations
INFLUENZA
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Eye disorders
DIPLOPIA
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Eye disorders
EYE PAIN
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Eye disorders
EYELID OEDEMA
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Eye disorders
LACRIMATION INCREASED
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Investigations
WEIGHT DECREASED
|
0.00%
0/3
|
0.00%
0/9
|
33.3%
2/6
|
|
Investigations
BLOOD BILIRUBIN INCREASED
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Cardiac disorders
SUPRAVENTRICULAR TACHYCARDIA
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Vascular disorders
HYPOTENSION
|
33.3%
1/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Vascular disorders
DEEP VEIN THROMBOSIS
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Vascular disorders
VENA CAVA THROMBOSIS
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Psychiatric disorders
INSOMNIA
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Psychiatric disorders
CONFUSIONAL STATE
|
0.00%
0/3
|
11.1%
1/9
|
16.7%
1/6
|
|
Nervous system disorders
TREMOR
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Nervous system disorders
HEADACHE
|
33.3%
1/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Nervous system disorders
DIZZINESS
|
33.3%
1/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Nervous system disorders
DYSGEUSIA
|
33.3%
1/3
|
22.2%
2/9
|
0.00%
0/6
|
|
Nervous system disorders
NEUROPATHY PERIPHERAL
|
33.3%
1/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Gastrointestinal disorders
NAUSEA
|
33.3%
1/3
|
55.6%
5/9
|
16.7%
1/6
|
|
Gastrointestinal disorders
ASCITES
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Gastrointestinal disorders
VOMITING
|
33.3%
1/3
|
22.2%
2/9
|
16.7%
1/6
|
|
Gastrointestinal disorders
DIARRHOEA
|
33.3%
1/3
|
11.1%
1/9
|
16.7%
1/6
|
|
Gastrointestinal disorders
DRY MOUTH
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Gastrointestinal disorders
DYSPHAGIA
|
0.00%
0/3
|
11.1%
1/9
|
33.3%
2/6
|
|
Gastrointestinal disorders
PROCTALGIA
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Gastrointestinal disorders
STOMATITIS
|
33.3%
1/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/3
|
33.3%
3/9
|
33.3%
2/6
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/3
|
22.2%
2/9
|
0.00%
0/6
|
|
Infections and infestations
FOLLICULITIS
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Infections and infestations
NASOPHARYNGITIS
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Infections and infestations
FUNGAL INFECTION
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Infections and infestations
ESCHERICHIA INFECTION
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Renal and urinary disorders
RENAL PAIN
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Renal and urinary disorders
POLLAKIURIA
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
ANOREXIA
|
66.7%
2/3
|
22.2%
2/9
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
HYPERNATRAEMIA
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.00%
0/3
|
33.3%
3/9
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
0.00%
0/3
|
0.00%
0/9
|
50.0%
3/6
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
0.00%
0/3
|
22.2%
2/9
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
DECUBITUS ULCER
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
EXFOLIATIVE RASH
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Reproductive system and breast disorders
SCROTAL PAIN
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
FALL
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
TENDON RUPTURE
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.00%
0/3
|
22.2%
2/9
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
NECK PAIN
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
FLANK PAIN
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
33.3%
1/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
33.3%
1/3
|
22.2%
2/9
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
HICCUPS
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
33.3%
1/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
DYSPHONIA
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
ASPIRATION
|
0.00%
0/3
|
0.00%
0/9
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
ATELECTASIS
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
SINUS DISORDER
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY TRACT CONGESTION
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
General disorders
FATIGUE
|
100.0%
3/3
|
44.4%
4/9
|
66.7%
4/6
|
|
General disorders
PYREXIA
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
|
General disorders
CHEST PAIN
|
33.3%
1/3
|
0.00%
0/9
|
0.00%
0/6
|
|
General disorders
MUCOSAL INFLAMMATION
|
0.00%
0/3
|
22.2%
2/9
|
0.00%
0/6
|
|
General disorders
TEMPERATURE INTOLERANCE
|
0.00%
0/3
|
11.1%
1/9
|
0.00%
0/6
|
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