A Phase I Study of Ixabepilone in Combination With Capecitabine in Japanese Patients With Metastatic Breast Cancer

A Phase I Study of Ixabepilone in Combination With Capecitabine in Japanese Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00568022

Enrollment

Registered

2007-12-05

Start date

2008-02-29

Completion date

2010-01-31

Last updated

2016-03-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Brief summary

The purpose of this study is to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase II dose of ixabepilone in combination with capecitabine in Japanese participants with metastatic breast cancer.

Interventions

DRUGIxabepilone

Ixabepilone: Intravenous (IV) Solution, IV, 32(40)mg/m\^2, once every 3 weeks, up to 6 cycles

DRUGCapecitabine

Capecitabine: Tablets, Oral, 1650(2000)mg/m\^2, twice daily for 2 weeks, one week off, up to 6 cycles

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

20 Years to No maximum

Healthy volunteers

Inclusion criteria

* Women ≥ 20 years * Histologically or cytologically confirmed diagnosis of adenocarcinoma originating in the breast

Exclusion criteria

* Number of prior chemotherapy lines of treatment in the metastatic setting ≥3

Design outcomes

Primary

Measure	Time frame	Description
Participants Experiencing Dose Limiting Toxicity (DLT)	From initiation of drug through last day of Cycle 2 (Day 42)	DLT was defined as any ixabepilone and/or capecitabine related events requiring study discontinuation during the first two treatment cycles.
Participants Achieving the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)	At the end of Cycle 2 (Day 42)	The MTD was defined as the highest dose evaluated for which less than 1/3 of the participants experienced DLT during the first two treatment cycles. If toxicities (e.g. hand-foot syndrome, existing peripheral neuropathy, etc.) occurred or became more severe in later cycles, the recommended Phase II dose was to be determined after due consideration of their severity.

Secondary

Measure	Time frame	Description
Mean Ixabepilone Maximum Plasma Concentration (Cmax) in One Dosing Interval	During Cycle 1 at specified timepoints (Day 1 to Day 8).	Cmax = maximum observed plasma concentration of ixabepilone as determined from participant serum samples in one dosing interval.
Mean Ixabepilone Area Under the Concentration Curve (AUC INF) in One Dosing Interval	During Cycle 1 at specified timepoints (Day 1 to Day 8).	AUC = the average area under the concentration curve (AUC \[INF\]) of ixabepilone as determined from participant serum samples in one dosing interval over 24 hours.
Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline to Day 42, continuously	AE = any new untoward medical occurrence/worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE = any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or 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, is an important medical event. Treatment-related=Possible, Probable, or Certain relationship to drug
Mean Ixabepilone Volume of Distribution at Steady State (Vss) in One Dosing Interval	During Cycle 1 at specified timepoints (Day 1 to Day 8).	Vss = volume of distribution at steady state determined from participant serum samples from one dosing interval.
Mean Ixabepilone Total Body Clearance (CLT) in One Dosing Interval	During Cycle 1 at specified timepoints (Day 1 to Day 8).	CLT = total body clearance as determined from participant serum samples in one dosing interval.
Mean Ixabepilone Terminal Elimination Half Life (T 1/2) in One Dosing Interval	During Cycle 1 at specified timepoints (Day 1 to Day 8).	T 1/2 = terminal elimination half life as determined from participant serum samples in one dosing interval.
Participant Tumor Response at Study Endpoint	At baseline and after every 42 days (every 2 21-day cycles) after baseline	Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) in which complete response (CR) = disappearance of all target lesions; partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions; and stable disease (SD) = small changes that do not meet above criteria.

Countries

Japan

Participant flow

Recruitment details

Participants were recruited from 4 sites in Japan.

Participants by arm

Arm	Count
Ixabepilone 32 mg/m^2 + Capecitabine 1650 mg/m^2/Day Ixabepilone 32 mg/m\^2 was administered via intravenous (IV) infusion over 3 hours on Day 1 of each 21-day treatment cycle. Capecitabine 1650 mg/m\^2/day was administered on Days 1 to 14 of each 21-day treatment cycle.	3
Ixabepilone 40 mg/m^2 + Capecitabine 1650 mg/m^2/Day Ixabepilone 40 mg/m\^2 was administered via intravenous (IV) infusion over 3 hours on Day 1 of each 21-day treatment cycle. Capecitabine 1650 mg/m\^2/day was administered on Days 1 to 14 of each 21-day treatment cycle.	3
Ixabepilone 40 mg/m^2 + Capecitabine 2000 mg/m^2/Day Ixabepilone 40 mg/m\^2 was administered via intravenous (IV) infusion over 3 hours on Day 1 of each 21-day treatment cycle. Capecitabine 2000 mg/m\^2/day was administered on Days 1 to 14 of each 21-day treatment cycle.	3
Total	9

Baseline characteristics

Characteristic	Ixabepilone 40 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Ixabepilone 40 mg/m^2 + Capecitabine 2000 mg/m^2/Day	Ixabepilone 32 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	1 Participants	0 Participants	1 Participants
Age, Categorical Between 18 and 65 years	3 Participants	2 Participants	3 Participants	8 Participants
Age, Continuous	52.7 years STANDARD_DEVIATION 4.73	52.7 years STANDARD_DEVIATION 20.26	54.0 years STANDARD_DEVIATION 13	53.1 years STANDARD_DEVIATION 12.28
Region of Enrollment Japan	3 participants	3 participants	3 participants	9 participants
Sex: Female, Male Female	3 Participants	3 Participants	3 Participants	9 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	3 / 3	3 / 3	3 / 3
serious Total, serious adverse events	0 / 3	1 / 3	1 / 3

Outcome results

Primary

Participants Achieving the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

The MTD was defined as the highest dose evaluated for which less than 1/3 of the participants experienced DLT during the first two treatment cycles. If toxicities (e.g. hand-foot syndrome, existing peripheral neuropathy, etc.) occurred or became more severe in later cycles, the recommended Phase II dose was to be determined after due consideration of their severity.

Time frame: At the end of Cycle 2 (Day 42)

Population: All participants treated at the highest dose level.

Arm	Measure	Group	Value (NUMBER)
Ixabepilone 32 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Participants Achieving the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)	Ixa 40 mg/m^2 + Cap 2000 mg/m^2 MTD	3 Participants
Ixabepilone 32 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Participants Achieving the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)	Ixa 40 mg/m^2 + Cap 2000 ng/m^2 RP2D	3 Participants

Primary

Participants Experiencing Dose Limiting Toxicity (DLT)

DLT was defined as any ixabepilone and/or capecitabine related events requiring study discontinuation during the first two treatment cycles.

Time frame: From initiation of drug through last day of Cycle 2 (Day 42)

Population: All participants who received at least 1 dose of either ixabepilone or capecitabine.

Arm	Measure	Value (NUMBER)
Ixabepilone 32 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Participants Experiencing Dose Limiting Toxicity (DLT)	0 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Participants Experiencing Dose Limiting Toxicity (DLT)	0 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 2000 mg/m^2/Day	Participants Experiencing Dose Limiting Toxicity (DLT)	0 Participants

Secondary

Adverse Events (AEs) and Serious Adverse Events (SAEs)

AE = any new untoward medical occurrence/worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE = any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or 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, is an important medical event. Treatment-related=Possible, Probable, or Certain relationship to drug

Time frame: Baseline to Day 42, continuously

Population: All participants who received at least 1 dose of either ixabepilone or capecitabine.

Arm	Measure	Group	Value (NUMBER)
Ixabepilone 32 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Related AEs	3 Participants
Ixabepilone 32 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Deaths	0 Participants
Ixabepilone 32 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Related SAEs	0 Participants
Ixabepilone 32 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs	3 Participants
Ixabepilone 32 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	0 Participants
Ixabepilone 32 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Discontinued Due to AEs	0 Participants
Ixabepilone 32 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Discontinued Due to SAEs	0 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Discontinued Due to AEs	0 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs	3 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Discontinued Due to SAEs	0 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Related AEs	3 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	1 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Related SAEs	1 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 1650 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Deaths	0 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 2000 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Deaths	0 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 2000 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Related SAEs	1 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 2000 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs	3 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 2000 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Discontinued Due to SAEs	0 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 2000 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Discontinued Due to AEs	0 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 2000 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	1 Participants
Ixabepilone 40 mg/m^2 + Capecitabine 2000 mg/m^2/Day	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Related AEs	3 Participants

Secondary

Mean Ixabepilone Area Under the Concentration Curve (AUC INF) in One Dosing Interval

AUC = the average area under the concentration curve (AUC \[INF\]) of ixabepilone as determined from participant serum samples in one dosing interval over 24 hours.