Stomach Neoplasms
Conditions
Brief summary
The purpose of this study was to determine whether ixabepilone is effective in the treatment of unresectable or metastatic gastric cancer in Asian participants.
Interventions
DRUGIxabepilone
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.
Sponsors
R-Pharm
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (RECIST) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response | Assessed every 6 weeks (± 1 week) starting from the first dose of study therapy until CR or PR (up to 12.1 weeks.) | 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 | From the date of first PR or CR assessment to the date of progression, death, or last tumor assessment (maximum: 4.1 months) | 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) | From the date of initiation of study therapy to the date of progression (up to 8.1 months). | 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). |
| 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 | 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) | 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 | 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). | 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 | 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). | 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. |
| Percentage of Participants With Disease Control Rate | 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) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Best Response as Assessed With Modified RECIST | 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) | 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. |
Countries
Hong Kong, Japan, Singapore, South Korea, Taiwan
Participant flow
Pre-assignment details
Of 58 participants enrolled in this study, 6 failed screening criteria, and 52 received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Ixabepilone 40 mg/m^2 IV ixabepilone 40 mg/m\^2 intravenous (IV), every 21 days, up to 8 cycles or until disease progression or development of intolerable toxicity. | 52 |
| Total | 52 |
Baseline characteristics
| Characteristic | Ixabepilone 40 mg/m^2 IV |
|---|---|
| Age, Customized < 50 years | 9 participants |
| Age, Customized >=50 years | 43 participants |
| Age, Customized < 65 years | 40 participants |
| Age, Customized >=65 years | 12 participants |
| Age, Customized | 56.5 years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 (normal activity) | 20 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 1 (symptoms, but fully ambulatory) | 32 participants |
| Race/Ethnicity, Customized Asian Other | 1 participants |
| Race/Ethnicity, Customized Chinese | 23 participants |
| Race/Ethnicity, Customized Japanese | 15 participants |
| Race/Ethnicity, Customized Korean | 13 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 51 / 52 |
| serious Total, serious adverse events | 30 / 52 |
Outcome results
Primary
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.
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)
Population: Response-evaluable participants: Participants who received at least 1 dose of ixabepilone with measurable disease at baseline and right cancer diagnosis (presence of histologic or cytologic diagnosis of advanced or metastatic adenocarcinoma originating in the stomach or gastroesophageal junction).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixabepilone 40 mg/m^2 IV | Percentage of Participants With Overall Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (RECIST) | 15.4 percentage of participants |
Secondary
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.
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)
Population: Participants who received at least 1 dose of ixabepilone and had either CR or PR. Participants who neither relapsed nor died were censored on the date of their last tumor assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone 40 mg/m^2 IV | Duration of Response | 3.1 months |
Secondary
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.
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)
Population: Participants who received at least 1 dose of study therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 40 mg/m^2 IV | 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 | Death (due to disease progression) | 16 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | Death (due to pneumonia) | 1 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | Death within 30 days of last dose of study therapy | 4 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | At least one SAE (Any GR) | 30 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | At least one SAE (GR 3-4) | 21 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | At least one DR SAE (Any GR) | 12 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | At least one DR SAE (GR 3-4) | 9 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | At least one AE (Any GR) | 52 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | At least one AE (GR 3-4) | 41 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | At least one DR AE (Any GR) | 50 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | At least one DR AE (GR 3-4) | 31 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | AEs leading to study drug discontinuation (Any GR) | 10 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | AEs leading to study drug discontinuation (GR 3-4) | 7 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | DRAEs leading to study drug discontinuation:Any GR | 4 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | DRAEs leading to study drug discontinuation: GR3-4 | 4 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | Any Peripheral Neuropathy (Any GR) | 33 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | Any Peripheral Neuropathy (GR 3-4) | 4 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | DR Peripheral Neuropathy (Any GR) | 32 participants |
| Ixabepilone 40 mg/m^2 IV | 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 | DR Peripheral Neuropathy (GR 3-4) | 4 participants |
Secondary
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.
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).
Population: Participants who received at least 1 dose of ixabepilone and had at least one measurement available during the study therapy period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | WBC GR1 | 6 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | WBC GR2 | 17 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | WBC GR3 | 20 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | WBC GR4 | 5 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | ANC GR1 | 4 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | ANC GR2 | 7 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | ANC GR3 | 16 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | ANC GR4 | 21 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | Platelet Count GR1 | 18 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | Platelet Count GR2 | 3 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | Platelet Count GR3 | 4 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | Platelet Count GR4 | 0 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | Hemoglobin GR1 | 17 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | Hemoglobin GR2 | 23 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | Hemoglobin GR3 | 11 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities | Hemoglobin GR4 | 0 participants |
Secondary
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.
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).
Population: Participants who received at least 1 dose of ixabepilone. n=number of participants with at least 1 measurement available during the study therapy period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | Creatinine GR1 (n=51) | 4 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | ALP GR1 (n=49) | 22 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | ALP GR2 (n=49) | 1 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | ALP GR3 (n=49) | 1 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | ALP GR4 (n=49) | 1 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | AST GR1 (n=49) | 9 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | AST GR2 (n=49) | 0 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | AST GR3 (n=49) | 0 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | AST GR4 (n=49) | 0 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | ALT GR1 (n=50) | 8 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | ALT GR2 (n=50) | 1 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | ALT GR3 (n=50) | 0 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | ALT GR4 (n=50) | 0 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | Total bilirubin GR1 (n=49) | 0 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | Total bilirubin GR2 (n=49) | 3 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | Total bilirubin GR3 (n=49) | 0 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | Total bilirubin GR4 (n=49) | 0 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | Creatinine GR2 (n=51) | 1 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | Creatinine GR3 (n=51) | 0 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities | Creatinine GR4 (n=51) | 0 participants |
Secondary
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.
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)
Population: Response-evaluable participants: Participants who received at least 1 dose of ixabepilone with measurable disease at baseline and right cancer diagnosis (presence of histologic or cytologic diagnosis of advanced or metastatic adenocarcinoma originating in the stomach or gastroesophageal junction).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixabepilone 40 mg/m^2 IV | Percentage of Participants With Disease Control Rate | 65.4 percentage of participants |
Secondary
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).
Time frame: From the date of initiation of study therapy to the date of progression (up to 8.1 months).
Population: Participants who received at least 1 dose of ixabepilone. Participants who died without reporting prior progression were considered to have progressed on their death day. Participants who did not progress or die were censored on their last tumor assessment day. Participants without on-study tumor assessments were censored at start date of therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone 40 mg/m^2 IV | Progression Free Survival (PFS) | 2.8 months |
Secondary
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.
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.)
Population: Participants who received at least 1 dose of study therapy and had a response of either CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone 40 mg/m^2 IV | Time to Response | 8.9 weeks |
Other Pre-specified
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.
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 (to a maximum follow up for tumor response of 30 weeks)
Population: Response-evaluable participants: Participants who received at least 1 dose of ixabepilone with measurable disease at baseline and right cancer diagnosis (presence of histologic or cytologic diagnosis of advanced or metastatic adenocarcinoma originating in the stomach or gastroesophageal junction).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Best Response as Assessed With Modified RECIST | Partial Response | 8 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Best Response as Assessed With Modified RECIST | Stable Disease | 26 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Best Response as Assessed With Modified RECIST | Progressive Disease | 15 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Best Response as Assessed With Modified RECIST | Unable to Determine (No tumor assessment) | 1 participants |
| Ixabepilone 40 mg/m^2 IV | Number of Participants With Best Response as Assessed With Modified RECIST | Unable to Determine (Other) | 2 participants |