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

• Time to Response [ Time Frame: Assessed every 6 weeks (± 1 week) starting from the first dose of study therapy until CR or PR (up to 12.1 weeks.) ] [ Designated as safety issue: No ]
  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.
• Duration of Response [ Time Frame: From the date of first PR or CR assessment to the date of progression, death, or last tumor assessment (maximum: 4.1 months) ] [ Designated as safety issue: No ]
  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.
• Progression Free Survival (PFS) [ Time Frame: From the date of initiation of study therapy to the date of progression (up to 8.1 months). ] [ Designated as safety issue: No ]
  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).
• Percentage of Participants With Disease Control Rate [ Time Frame: 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) ] [ Designated as safety issue: No ]
  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.
• 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 [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  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.
• Number of Participants With Hematology Abnormalities [ Time Frame: 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). ] [ Designated as safety issue: Yes ]
  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.
• Number of Participants With Serum Chemistry Abnormalities [ Time Frame: 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). ] [ Designated as safety issue: Yes ]
  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.

• To assess duration of response and time to response for this study population [ Time Frame: Tumor assessment every other cycle (about 6 weekly) till end of study period ] [ Designated as safety issue: No ]
• To assess disease control rate for this study population [ Time Frame: Tumor assessment every other cycle (about 6 weekly) till end of study period ] [ Designated as safety issue: Yes ]
• To assess progression free survival for this study population [ Time Frame: Tumor assessment every other cycle (about 6 weekly) till end of study period ] [ Designated as safety issue: Yes ]
• To assess safety and tolerability of ixabepilone [ Time Frame: Tumor assessment every other cycle (about 6 weekly) till end of study period ] [ Designated as safety issue: Yes ]

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

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