Metastatic Breast Cancer, Triple Negative Locally Advanced Non-resectable Breast Cancer
Conditions
Brief summary
The purpose of this study was to estimate the response rate of ixabepilone monotherapy, and the combination of ixabepilone plus cetuximab as first-line treatment of female subjects with triple negative (estrogen receptor \[ER\], progesterone receptor \[PR\], Human Epidermal Growth Factor Receptor 2 \[HER2\] negative) locally advanced non-resectable and/or metastatic breast cancer
Interventions
DRUGixabepilone
injection, intravenous (IV), until unacceptable toxicity or progression or 15 months after the Last Subject First Visit (LSFV), whichever comes first. Ixabepilone 40 mg/m\^2 was administered as a 3-hour IV continuous infusion on Day 1 in a 21-day cycle provided the participant met the re-treatment criteria.
DRUGixabepilone + cetuximab
Ixabepilone: injection, IV, until unacceptable toxicity or progression or 15 months after the LSFV, whichever comes first. Ixabepilone 40 mg/m\^2 was administered as a 3-hour IV continuous infusion on Day 1 in a 21-day cycle provided the participant meets the re-treatment criteria. Cetuximab: injection, IV, until unacceptable toxicity or progression or 15 months after the LSFV, whichever comes first. Cetuximab 400 mg/m\^2 was administered as a 2-hour IV loading dose via in-line filtration with an infusion pump, gravity drip, or a syringe pump on Day 1 of first cycle then 250 mg/m\^2 1-hour IV once a week, i.e. on Days 1, 8, and 15 of each cycle provided the participant meets the re-treatment criteria.
Sponsors
R-Pharm
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female subjects with triple negative (ER, PR, and HER2 negative) locally advanced non-resectable and/or metastatic breast cancer * Prior adjuvant or neoadjuvant anthracycline-based chemotherapy
Exclusion criteria
* Tumors that are fluorescence in situ hybridization test (FISH) positive or immunohistochemistry (IHC) 3+ * Neuropathy \> Grade 1 * Prior systemic therapy for metastatic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR; Using Response Evaluation Criteria in Solid Tumors [RECIST]) | Assessed every 6 weeks for first 12 months from randomization thereafter every 3 months until disease progression (maximum participant objective response of 18.3 weeks) | The participant had an OR if her best overall response (BOR) during the study was either a complete response (CR) or a partial response (PR) according to the RECIST as determined by the investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions. Confidence interval (CI) was Computed using Clopper-Pearson method. |
| Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Assessed at 6 week intervals for first 12 months from randomization, thereafter every 3 months (to a maximum follow-up for tumor response of 17 months). | PD = At least a 20% increase in the sum of LD of target lesions in reference to the smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall; Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | From the date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 15.6 months) | Defined as period from the time that measurement criteria are first met for CR or PR until first date of documented PD or death. Estimated using the Kaplan-Meier product-limit method; CI was computed using Brookmeyer and Crowley method. CR: Disappearance of all target and non-target lesions. PR: At least 30% reduction from baseline in the sum of LD of all target lesions with reference to baseline sum LD. PD: At least 20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall. |
| 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 15 weeks (range: 3-54 weeks for ixabepilone arm; 3-36 weeks for ixabepilone+cetuximab arm) | 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. Other reasons for death included hepatic failure and respiratory distress. |
| Progression Free Survival (PFS) | From the date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 17 months) | PFS is defined as the time interval from date of randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression. The PFS was estimated using the Kaplan-Meier product-limit method, and a two-sided 95% CI for the median PFS time was computed using the method of Brookmeyer and Crowley. PD: At least 20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall. |
| Number of Participants With Serum Chemistry Abnormalities | Assessed prior to 1st cycle, at beginning of each cycle, weekly (cetuximab treatment), and every 4 weeks within 30 days after last dose of study drug. Median time on ixapebilone therapy: 15 weeks (range:3-54:ixabepilone arm;3-36:ixapebilone+cetuximab arm) | 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. Alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase: GR1=\>ULN-2.5\*ULN (upper limit of normal); 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. |
| Number of Participants With Hematology Abnormalities | Assessed prior to 1st cycle, at beginning of each cycle, weekly (cetuximab treatment), and every 4 weeks within 30 days after last dose of study drug. Median time on ixapebilone therapy: 15 weeks (range:3-54:ixabepilone arm;3-36:ixapebilone+cetuximab arm) | 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. Hemoglobin:GR1=\<LLN-10.0g/dL; GR2=\<10.0-8.0g/dL; GR3:\<8.0-6.5g/dL, GR4:\<6.5g/dL. 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. 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. 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. LLN=lower limit of normal. |
| Time to Response | Assessed every 6 weeks for first 12 months from randomization thereafter every 3 months until CR or PR (maximum participant time to response of 18.3 weeks.) | Time to response is defined as the time from the date of start of treatment until measurement criteria are first met for PR or CR (whichever is recorded first). CR: Disappearance of all target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all target lesions with reference to the baseline sum LD. Time to response was estimated using the Kaplan-Meier product-limit method. |
Countries
Austria, Czechia, France, Greece, Italy, Poland, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ixabepilone 40 mg/m^2 ixabepilone 40 mg/m\^2 every 3 weeks | 40 |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 cetuximab 400 mg/m\^2 loading dose then 250 mg/m\^2 weekly + ixabepilone 40 mg/m\^2 every 3 weeks | 39 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Never Treated (Not met study criteria) | 0 | 1 |
| Overall Study | Never Treated (Randomized in error) | 0 | 1 |
Baseline characteristics
| Characteristic | Ixabepilone 40 mg/m^2 | Total | Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 |
|---|---|---|---|
| Age, Customized < 65 | 35 participants | 67 participants | 32 participants |
| Age, Customized >=65 | 5 participants | 12 participants | 7 participants |
| Age, Customized | 53.0 years | 53.0 years | 50.0 years |
| Karnofsky Performance Status 100 | 23 participants | 46 participants | 23 participants |
| Karnofsky Performance Status 80 | 11 participants | 21 participants | 10 participants |
| Karnofsky Performance Status 90 | 6 participants | 11 participants | 5 participants |
| Karnofsky Performance Status Not Reported | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black/African American | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White | 39 participants | 78 participants | 39 participants |
| Setting of Prior Chemotherapy Adjuvant and Neo-adjuvant | 8 participants | 11 participants | 3 participants |
| Setting of Prior Chemotherapy Adjuvant therapy | 28 participants | 50 participants | 22 participants |
| Setting of Prior Chemotherapy Neo-adjuvant therapy | 20 participants | 40 participants | 20 participants |
| Sex/Gender, Customized Female | 40 participants | 79 participants | 39 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 40 | 37 / 37 |
| serious Total, serious adverse events | 9 / 40 | 12 / 37 |
Outcome results
Primary
Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST)
PD = At least a 20% increase in the sum of LD of target lesions in reference to the smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall; Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions.
Time frame: Assessed at 6 week intervals for first 12 months from randomization, thereafter every 3 months (to a maximum follow-up for tumor response of 17 months).
Population: All randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 40 mg/m^2 | Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Partial Response | 9 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Progressive Disease | 9 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Complete Response | 3 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Stable Disease | 17 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Unable to determine | 2 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Never Treated | 0 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Unable to determine | 1 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Complete Response | 0 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Partial Response | 14 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Stable Disease | 12 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Progressive Disease | 10 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) | Never Treated | 2 participants |
Primary
Percentage of Participants With Objective Response (OR; Using Response Evaluation Criteria in Solid Tumors [RECIST])
The participant had an OR if her best overall response (BOR) during the study was either a complete response (CR) or a partial response (PR) according to the RECIST as determined by the investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions. Confidence interval (CI) was Computed using Clopper-Pearson method.
Time frame: Assessed every 6 weeks for first 12 months from randomization thereafter every 3 months until disease progression (maximum participant objective response of 18.3 weeks)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixabepilone 40 mg/m^2 | Percentage of Participants With Objective Response (OR; Using Response Evaluation Criteria in Solid Tumors [RECIST]) | 30.0 percentage of participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Percentage of Participants With Objective Response (OR; Using Response Evaluation Criteria in Solid Tumors [RECIST]) | 35.9 percentage of participants |
Secondary
Duration of Response
Defined as period from the time that measurement criteria are first met for CR or PR until first date of documented PD or death. Estimated using the Kaplan-Meier product-limit method; CI was computed using Brookmeyer and Crowley method. CR: Disappearance of all target and non-target lesions. PR: At least 30% reduction from baseline in the sum of LD of all target lesions with reference to baseline sum LD. PD: At least 20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall.
Time frame: From the date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 15.6 months)
Population: Randomized participants with response of CR or PR. Participants who did not relapse or die were censored on the date of their last tumor assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone 40 mg/m^2 | Duration of Response | 4.5 months |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Duration of Response | 4.5 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. Other reasons for death included hepatic failure and respiratory distress.
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 15 weeks (range: 3-54 weeks for ixabepilone arm; 3-36 weeks for ixabepilone+cetuximab arm)
Population: All treated participants: Participants who received any treatment (ixabepilone or cetuximab).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 40 mg/m^2 | 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 | Deaths due to Other Reasons | 0 participants |
| Ixabepilone 40 mg/m^2 | 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 Grade) | 40 participants |
| Ixabepilone 40 mg/m^2 | 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 (Grade 3 to 4) | 4 participants |
| Ixabepilone 40 mg/m^2 | 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 (Grade 3 to 4) | 21 participants |
| Ixabepilone 40 mg/m^2 | 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 | Deaths due to Disease Progression | 8 participants |
| Ixabepilone 40 mg/m^2 | 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 Related AE | 37 participants |
| Ixabepilone 40 mg/m^2 | 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 Related SAE (Any Grade) | 3 participants |
| Ixabepilone 40 mg/m^2 | 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 Related AE (Grade 3 to 4) | 18 participants |
| Ixabepilone 40 mg/m^2 | 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 Grade) | 9 participants |
| Ixabepilone 40 mg/m^2 | 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 discontinuation (Any Grade) | 8 participants |
| Ixabepilone 40 mg/m^2 | 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 Related SAE (Grade 3 to 4) | 2 participants |
| Ixabepilone 40 mg/m^2 | 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 discontinuation (Grade 3 to 4) | 3 participants |
| Ixabepilone 40 mg/m^2 | 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 | All Deaths | 8 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 discontinuation (Grade 3 to 4) | 7 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 | All Deaths | 9 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 | Deaths due to Disease Progression | 7 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 | Deaths due to Other Reasons | 2 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 Grade) | 12 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 (Grade 3 to 4) | 11 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 Related SAE (Any Grade) | 6 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 Related SAE (Grade 3 to 4) | 6 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 Grade) | 37 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 (Grade 3 to 4) | 25 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 Related AE | 37 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 Related AE (Grade 3 to 4) | 22 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | 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 discontinuation (Any Grade) | 13 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. Hemoglobin:GR1=\<LLN-10.0g/dL; GR2=\<10.0-8.0g/dL; GR3:\<8.0-6.5g/dL, GR4:\<6.5g/dL. 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. 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. 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. LLN=lower limit of normal.
Time frame: Assessed prior to 1st cycle, at beginning of each cycle, weekly (cetuximab treatment), and every 4 weeks within 30 days after last dose of study drug. Median time on ixapebilone therapy: 15 weeks (range:3-54:ixabepilone arm;3-36:ixapebilone+cetuximab arm)
Population: Treated participants: Participants who received any treatment (ixabepilone or cetuximab). n=number of participants with measures available at the time.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | White Blood cell (WBC) GR 1-4 | 33 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | WBC GR 3-4 | 13 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | Absolute Neutrophil Count(ANC) GR 1-4 (n=39; n=37) | 33 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | ANC GR 3-4 (n=39; n=37) | 19 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | Platelet Count GR 1-4 (n=39; n=37) | 11 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | Platelet Count GR 3-4 (n=39; n=37) | 0 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | Hemoglobin GR 1-4 | 29 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | Hemoglobin GR 3-4 | 0 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | Hemoglobin GR 3-4 | 0 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | White Blood cell (WBC) GR 1-4 | 34 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | Platelet Count GR 1-4 (n=39; n=37) | 4 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | WBC GR 3-4 | 16 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | Hemoglobin GR 1-4 | 27 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | Absolute Neutrophil Count(ANC) GR 1-4 (n=39; n=37) | 31 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | Platelet Count GR 3-4 (n=39; n=37) | 0 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Hematology Abnormalities | ANC GR 3-4 (n=39; n=37) | 18 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. Alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase: GR1=\>ULN-2.5\*ULN (upper limit of normal); 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.
Time frame: Assessed prior to 1st cycle, at beginning of each cycle, weekly (cetuximab treatment), and every 4 weeks within 30 days after last dose of study drug. Median time on ixapebilone therapy: 15 weeks (range:3-54:ixabepilone arm;3-36:ixapebilone+cetuximab arm)
Population: Treated participants: Participants who received any treatment (ixabepilone or cetuximab). n=number of participants with measures available at the time.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Alkaline Phosphatase (ALP) GR 1-4 (n=38; n=35) | 9 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | ALP GR 3-4 (n=38; n=35) | 0 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Alanine Aminotransferase (ALT) GR 1-4 (n=39; n=35) | 10 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | ALT GR 3-4 (n=39; n=35) | 1 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Aspartate Aminotransferase (AST) GR1-4(n=39; n=35) | 11 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | AST GR 3-4 (n=39; n=35) | 1 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Total Bilirubin GR 1-4 (n=39; n=35) | 1 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Total Bilirubin GR 3-4 (n=39; n=35) | 1 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Creatinine GR 1-4 (n=40; n=36) | 3 participants |
| Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Creatinine GR 3-4 (n=40; n=36) | 0 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Total Bilirubin GR 3-4 (n=39; n=35) | 0 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Alkaline Phosphatase (ALP) GR 1-4 (n=38; n=35) | 17 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | AST GR 3-4 (n=39; n=35) | 3 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | ALP GR 3-4 (n=38; n=35) | 1 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Creatinine GR 3-4 (n=40; n=36) | 0 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Alanine Aminotransferase (ALT) GR 1-4 (n=39; n=35) | 18 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Total Bilirubin GR 1-4 (n=39; n=35) | 3 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | ALT GR 3-4 (n=39; n=35) | 0 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Creatinine GR 1-4 (n=40; n=36) | 1 participants |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Number of Participants With Serum Chemistry Abnormalities | Aspartate Aminotransferase (AST) GR1-4(n=39; n=35) | 17 participants |
Secondary
Progression Free Survival (PFS)
PFS is defined as the time interval from date of randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression. The PFS was estimated using the Kaplan-Meier product-limit method, and a two-sided 95% CI for the median PFS time was computed using the method of Brookmeyer and Crowley. PD: At least 20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall.
Time frame: From the date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 17 months)
Population: All randomized participants. Participants who did not progress or die were censored on the date of their last tumor assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone 40 mg/m^2 | Progression Free Survival (PFS) | 4.1 months |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Progression Free Survival (PFS) | 4.1 months |
Secondary
Time to Response
Time to response is defined as the time from the date of start of treatment until measurement criteria are first met for PR or CR (whichever is recorded first). CR: Disappearance of all target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all target lesions with reference to the baseline sum LD. Time to response was estimated using the Kaplan-Meier product-limit method.
Time frame: Assessed every 6 weeks for first 12 months from randomization thereafter every 3 months until CR or PR (maximum participant time to response of 18.3 weeks.)
Population: Randomized participants with response of CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone 40 mg/m^2 | Time to Response | 8.8 weeks |
| Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 | Time to Response | 6.5 weeks |