Study of Ixabepilone in Asian Subjects With Unresectable or Metastatic Gastric Cancer

A Phase II Study of Ixabepilone in Asian Subjects With Unresectable or Metastatic Gastric Cancer Previously Treated With Fluoropyrimidine-based Chemotherapy

The purpose of this study was to determine whether ixabepilone is effective in the treatment of unresectable or metastatic gastric cancer in Asian participants.

Study Overview

• Status: Completed
• Conditions: Stomach Neoplasms
• Intervention / Treatment: Drug: Ixabepilone

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong, B
    • Local Institution
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 4648681
      • Local Institution
  • Shizuoka
    • Sunto-Gun, Shizuoka, Japan, 4118777
      • Local Institution
• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Local Institution
  • Seoul, Korea, Republic of, 138-736
    • Local Institution
  • Seoul, Korea, Republic of, 136-705
    • Local Institution
• Singapore
  • Singapore, Singapore, 169610
    • Local Institution
• Taiwan
  • Taipei, Taiwan, 112
    • Local Institution
  • Taoyuan Hsien, Taiwan, 333
    • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed gastric carcinoma originating from the stomach or gastroesophageal junction
• Must have unresectable or metastatic disease
• Asian ethnicity
• Must have failed prior fluoropyrimidine-based chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• measurable disease by with Response Evaluation Criteria in Solid Tumors (RECIST) guidelines

Exclusion Criteria:

• >1 prior chemotherapy regimen in the metastatic setting or >2 prior chemotherapy if subject also received adjuvant therapy
• Receipt of prior ixabepilone
• ECOG ≥2
• Known brain or meningeal metastasis
• Known viral hepatitis
• Prior taxane therapy
• Uncontrolled non-cancer related medical condition
• Second malignancy
• Peripheral neuropathy ≥ grade 2
• Inadequate hematologic, renal and hepatic function

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

Drug: Ixabepilone; Vial, Injection, Intravenous (IV), 40 mg/m^2, Every 21 days, Up to 8 cycles or until disease progression or intolerable toxicity. Additional treatment was given in agreement by both the investigator and sponsor. Ixabepilone 40 mg/m^2 was administered as a 3-hour IV infusion on Day 1 of each 21-day (3 week) cycle provided the participant met the retreatment criteria.; Other Names: BMS-247550; Ixempra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Overall Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (RECIST)	Percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) according to modified RECIST, as determined by investigator. CR: Disappearance of all evidence of target and non-target lesions. In case of lymph node, the lesions short axis of all nodes measuring <10 mm. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. A 2-sided confidence interval (CI) was computed using Clopper-Pearson method.	During treatment, assessed every 6 weeks (± 1 week) starting from the 1st dose of therapy until disease progression, or development of intolerable toxicity, for a maximum of 8 cycles (maximum time that any participant was on therapy was 30 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Response	Time to response is defined as the time in weeks from the first dose of study therapy until measurement criteria are first met for PR or CR (whichever status is recorded first). CR: Disappearance of all evidence of target and non-target lesions. In case of lymph node lesions, the short axis of all nodes should measure <10 mm. PR: At least 30% reduction from baseline in the sum of the LD of all target lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks of initial assessment.	Assessed every 6 weeks (± 1 week) starting from the first dose of study therapy until CR or PR (up to 12.1 weeks.)
Duration of Response	Defined as the period in months from the time measurement criteria are first met for PR or CR until the first date of documented PD or death. Refer to outcome measure 1 for CR and PR. PD=≥20% increase in the sum of LD of target lesions and an absolute increase of at least 5 mm of tumor size in reference to the smallest sum LD recorded at or following baseline or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions. Estimated by Kaplan-Meier product limit method and a 2-sided 95% CI for median duration was computed by Brookmeyer and Crowley method.	From the date of first PR or CR assessment to the date of progression, death, or last tumor assessment (maximum: 4.1 months)
Progression Free Survival (PFS)	PFS=the time interval from date of randomization to the earliest (first) progression or date of death. Participants who progressed or died were counted as events. PD=≥20% increase in sum of LD of target lesions and an absolute increase ≥5 mm in tumor size in reference to the smallest sum LD recorded at or following baseline or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions. Estimated using the Kaplan-Meier product-limit method for all treated participants and a 2-sided 95% CI for the median PFS was computed by Brookmeyer and Crowley method).	From the date of initiation of study therapy to the date of progression (up to 8.1 months).
Percentage of Participants With Disease Control Rate	Defined as percentage of participants whose best response was PR, CR, or SD as determined by the investigator. SD=Neither PR or PD are met, taking the smallest sum of the LD recorded at baseline as reference. Refer to outcome measure 1 for definition of CR or PR and refer to outcome measure 4 for definition of PD. A 2-sided 95% CI was computed using Clopper-Pearson method.	During treatment, assessed every 6 weeks (± 1 week) starting from the 1st dose of therapy until disease progression, or development of intolerable toxicity, for a maximum of 8 cycles (maximum time that any participant was on therapy was 30 weeks)
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0	AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization. Grade (GR) 3=Severe; and GR4=Life-threatening or disabling. DR=Drug-related. Any Peripheral Neuropathy includes peripheral sensory and motor neuropathies, including muscle weakness, and hypoaesthesia.	Assessed from the date of first dose until at least 30 days after the last dose of study drug. Median time on ixapebilone therapy was 10.5 weeks (range: 3 to 30 weeks)
Number of Participants With Hematology Abnormalities	Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. White blood cell (WBC):GR1=<LLN-3.0*10^9/L; GR2=<3.0-2.0*10^9/L; GR3=<2.0-1.0*10^9/L; GR4=<1.0*10^9/L. Absolute Neutrophil Count (ANC):GR1=<LLN-1.5*10^9 /L; GR2=<1.5-1.0*10^9/L; GR3=<1.0-0.5*10^9/L; GR4=<0.5*10^9/L. Platelets:GR1=<LLN-75.0*10^9/L; GR2=<75.0-50.0*10^9/L; GR3=<50.0-25.0*10^9/L, GR4=<25.0*10^9/L. Hemoglobin:GR1=<LLN-10.0g/dL; GR2=<10.0-8.0g/dL; GR3=<8.0-6.5g/dL, GR4=<6.5g/dL. LLN=lower limit of normal.	Assessed once every week for first 3 weeks, as clinically indicated, start of each 3 week cycle (maximum time that any participant was on therapy was 30 weeks).
Number of Participants With Serum Chemistry Abnormalities	Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST): GR1=>ULN-2.5*ULN; GR2=>2.5-5.0*ULN; GR3=>5.0-20.0*ULN; GR4=>20.0*ULN. Total bilirubin: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3-10*ULN, GR4=>10*ULN. Creatinine: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3.0-6.0*ULN, GR4=>6.0*ULN. ULN=upper limit of normal.	Assessed within 2 weeks of first dose and every 3 weeks before therapy dose (maximum time that any participant was on therapy was 30 weeks).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Best Response as Assessed With Modified RECIST	Best overall response that any participant can have is the best response recorded from the start of treatment until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). PR: At least 30% reduction from baseline in the sum of the LD of all target lesions. PR criteria should be met again after 4 weeks and before 6 weeks. Stable disease (SD)=Neither PR or progressive disease (PD) are met, taking the smallest sum of the LD recorded at baseline as reference. Refer to outcome measure 4 for definition of PD.	During treatment, assessed every 6 weeks (± 1 week) starting from the 1st dose of therapy until disease progression, or development of intolerable toxicity, for a maximum of 8 cycles (to a maximum follow up for tumor response of 30 weeks)

Collaborators and Investigators

• Sponsor: R-Pharm

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: September 23, 2009
• First Submitted That Met QC Criteria: September 23, 2009
• First Posted (Estimate): September 24, 2009

Study Record Updates

• Last Update Posted (Actual): October 28, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: CA163-200