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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Ixabepilone; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 540-0006
    • Local Institution
  • Ehime
    • Matsuyama-Shi, Ehime, Japan, 7910280
      • Local Institution
  • Gunma
    • Maebashi-Shi, Gunma, Japan, 371-8511
      • Local Institution
  • Shizuoka
    • Sunto-Gun, Shizuoka, Japan, 411-8777
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ixabepilone + Capecitabine	Drug: Ixabepilone; Ixabepilone: Intravenous (IV) Solution, IV, 32(40)mg/m^2, once every 3 weeks, up to 6 cycles; Other Names: BMS-247550; IXEMPRA; Drug: Capecitabine; Capecitabine: Tablets, Oral, 1650(2000)mg/m^2, twice daily for 2 weeks, one week off, up to 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From initiation of drug through last day of Cycle 2 (Day 42)
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.	At the end of Cycle 2 (Day 42)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Baseline to Day 42, continuously
Participant Tumor Response at Study Endpoint	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.	At baseline and after every 42 days (every 2 21-day cycles) after baseline
Mean Ixabepilone Maximum Plasma Concentration (Cmax) in One Dosing Interval	Cmax = maximum observed plasma concentration of ixabepilone as determined from participant serum samples in one dosing interval.	During Cycle 1 at specified timepoints (Day 1 to Day 8).
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.	During Cycle 1 at specified timepoints (Day 1 to Day 8).
Mean Ixabepilone Terminal Elimination Half Life (T 1/2) in One Dosing Interval	T 1/2 = terminal elimination half life as determined from participant serum samples in one dosing interval.	During Cycle 1 at specified timepoints (Day 1 to Day 8).
Mean Ixabepilone Volume of Distribution at Steady State (Vss) in One Dosing Interval	Vss = volume of distribution at steady state determined from participant serum samples from one dosing interval.	During Cycle 1 at specified timepoints (Day 1 to Day 8).
Mean Ixabepilone Total Body Clearance (CLT) in One Dosing Interval	CLT = total body clearance as determined from participant serum samples in one dosing interval.	During Cycle 1 at specified timepoints (Day 1 to Day 8).

Collaborators and Investigators

• Sponsor: R-Pharm

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: December 3, 2007
• First Submitted That Met QC Criteria: December 4, 2007
• First Posted (Estimate): December 5, 2007

Study Record Updates

• Last Update Posted (Estimate): March 10, 2016
• Last Update Submitted That Met QC Criteria: February 9, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: CA163-117