Trial Outcomes & Findings for Randomized Phase II Study of Ixabepilone Alone and Ixabepilone Plus Cetuximab as First-Line Treatment for Female Subjects With Triple Negative Locally Advanced Non-resectable and/or Metastatic Breast Cancer (NCT NCT00633464)

Last Updated: 2016-03-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

79 participants

Primary outcome timeframe

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)

Results posted on

2016-03-10

Participant Flow

Participant milestones

Participant milestones
Measure	Ixabepilone 40 mg/m^2 ixabepilone 40 mg/m\^2 every 3 weeks	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
Overall Study STARTED	40	39
Overall Study Treated	40	37
Overall Study COMPLETED	40	37
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Ixabepilone 40 mg/m^2 ixabepilone 40 mg/m\^2 every 3 weeks	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
Overall Study Never Treated (Not met study criteria)	0	1
Overall Study Never Treated (Randomized in error)	0	1

Baseline Characteristics

Randomized Phase II Study of Ixabepilone Alone and Ixabepilone Plus Cetuximab as First-Line Treatment for Female Subjects With Triple Negative Locally Advanced Non-resectable and/or Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ixabepilone 40 mg/m^2 n=40 Participants ixabepilone 40 mg/m\^2 every 3 weeks	Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 n=39 Participants cetuximab 400 mg/m\^2 loading dose then 250 mg/m\^2 weekly + ixabepilone 40 mg/m\^2 every 3 weeks	Total n=79 Participants Total of all reporting groups
Age, Customized	53.0 years n=5 Participants	50.0 years n=7 Participants	53.0 years n=5 Participants
Age, Customized < 65	35 participants n=5 Participants	32 participants n=7 Participants	67 participants n=5 Participants
Age, Customized >=65	5 participants n=5 Participants	7 participants n=7 Participants	12 participants n=5 Participants
Sex/Gender, Customized Female	40 participants n=5 Participants	39 participants n=7 Participants	79 participants n=5 Participants
Race/Ethnicity, Customized White	39 participants n=5 Participants	39 participants n=7 Participants	78 participants n=5 Participants
Race/Ethnicity, Customized Black/African American	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Karnofsky Performance Status 100	23 participants n=5 Participants	23 participants n=7 Participants	46 participants n=5 Participants
Karnofsky Performance Status 90	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
Karnofsky Performance Status 80	11 participants n=5 Participants	10 participants n=7 Participants	21 participants n=5 Participants
Karnofsky Performance Status Not Reported	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Setting of Prior Chemotherapy Adjuvant therapy	28 participants n=5 Participants	22 participants n=7 Participants	50 participants n=5 Participants
Setting of Prior Chemotherapy Neo-adjuvant therapy	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants
Setting of Prior Chemotherapy Adjuvant and Neo-adjuvant	8 participants n=5 Participants	3 participants n=7 Participants	11 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ixabepilone 40 mg/m^2 n=40 Participants ixabepilone 40 mg/m\^2 every 3 weeks	Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 n=39 Participants cetuximab 400 mg/m\^2 loading dose then 250 mg/m\^2 weekly + ixabepilone 40 mg/m\^2 every 3 weeks
Percentage of Participants With Objective Response (OR; Using Response Evaluation Criteria in Solid Tumors [RECIST])	30.0 percentage of participants Interval 16.6 to 46.5	35.9 percentage of participants Interval 21.2 to 52.8

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ixabepilone 40 mg/m^2 n=40 Participants ixabepilone 40 mg/m\^2 every 3 weeks	Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 n=39 Participants cetuximab 400 mg/m\^2 loading dose then 250 mg/m\^2 weekly + ixabepilone 40 mg/m\^2 every 3 weeks
Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) Complete Response	3 participants	0 participants
Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) Partial Response	9 participants	14 participants
Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) Stable Disease	17 participants	12 participants
Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) Progressive Disease	9 participants	10 participants
Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) Never Treated	0 participants	2 participants
Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) Unable to determine	2 participants	1 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ixabepilone 40 mg/m^2 n=40 Participants ixabepilone 40 mg/m\^2 every 3 weeks	Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 n=39 Participants cetuximab 400 mg/m\^2 loading dose then 250 mg/m\^2 weekly + ixabepilone 40 mg/m\^2 every 3 weeks
Progression Free Survival (PFS)	4.1 months Interval 3.0 to 4.9	4.1 months Interval 2.7 to 6.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ixabepilone 40 mg/m^2 n=12 Participants ixabepilone 40 mg/m\^2 every 3 weeks	Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 n=14 Participants cetuximab 400 mg/m\^2 loading dose then 250 mg/m\^2 weekly + ixabepilone 40 mg/m\^2 every 3 weeks
Time to Response	8.8 weeks Interval 5.1 to 12.0	6.5 weeks Interval 5.1 to 18.3

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ixabepilone 40 mg/m^2 n=12 Participants ixabepilone 40 mg/m\^2 every 3 weeks	Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 n=14 Participants cetuximab 400 mg/m\^2 loading dose then 250 mg/m\^2 weekly + ixabepilone 40 mg/m\^2 every 3 weeks
Duration of Response	4.5 months Interval 3.0 to 8.7	4.5 months Interval 3.4 to 6.9

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Ixabepilone 40 mg/m^2 n=40 Participants ixabepilone 40 mg/m\^2 every 3 weeks	Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 n=37 Participants cetuximab 400 mg/m\^2 loading dose then 250 mg/m\^2 weekly + ixabepilone 40 mg/m\^2 every 3 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 All Deaths	8 participants	9 participants
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	2 participants
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	6 participants
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	25 participants
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	7 participants
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	12 participants
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	11 participants
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	6 participants
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	37 participants
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	37 participants
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	22 participants
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	13 participants
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	7 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ixabepilone 40 mg/m^2 n=40 Participants ixabepilone 40 mg/m\^2 every 3 weeks	Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 n=37 Participants cetuximab 400 mg/m\^2 loading dose then 250 mg/m\^2 weekly + ixabepilone 40 mg/m\^2 every 3 weeks
Number of Participants With Hematology Abnormalities Platelet Count GR 1-4 (n=39; n=37)	11 participants	4 participants
Number of Participants With Hematology Abnormalities Hemoglobin GR 1-4	29 participants	27 participants
Number of Participants With Hematology Abnormalities Hemoglobin GR 3-4	0 participants	0 participants
Number of Participants With Hematology Abnormalities White Blood cell (WBC) GR 1-4	33 participants	34 participants
Number of Participants With Hematology Abnormalities WBC GR 3-4	13 participants	16 participants
Number of Participants With Hematology Abnormalities Absolute Neutrophil Count(ANC) GR 1-4 (n=39; n=37)	33 participants	31 participants
Number of Participants With Hematology Abnormalities ANC GR 3-4 (n=39; n=37)	19 participants	18 participants
Number of Participants With Hematology Abnormalities Platelet Count GR 3-4 (n=39; n=37)	0 participants	0 participants

SECONDARY outcome

Population: Treated participants: Participants who received any treatment (ixabepilone or cetuximab). n=number of participants with measures available at the time.

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.

Outcome measures

Outcome measures
Measure	Ixabepilone 40 mg/m^2 n=40 Participants ixabepilone 40 mg/m\^2 every 3 weeks	Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 n=37 Participants cetuximab 400 mg/m\^2 loading dose then 250 mg/m\^2 weekly + ixabepilone 40 mg/m\^2 every 3 weeks
Number of Participants With Serum Chemistry Abnormalities ALT GR 3-4 (n=39; n=35)	1 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities Aspartate Aminotransferase (AST) GR1-4(n=39; n=35)	11 participants	17 participants
Number of Participants With Serum Chemistry Abnormalities Creatinine GR 1-4 (n=40; n=36)	3 participants	1 participants
Number of Participants With Serum Chemistry Abnormalities Alkaline Phosphatase (ALP) GR 1-4 (n=38; n=35)	9 participants	17 participants
Number of Participants With Serum Chemistry Abnormalities ALP GR 3-4 (n=38; n=35)	0 participants	1 participants
Number of Participants With Serum Chemistry Abnormalities Alanine Aminotransferase (ALT) GR 1-4 (n=39; n=35)	10 participants	18 participants
Number of Participants With Serum Chemistry Abnormalities AST GR 3-4 (n=39; n=35)	1 participants	3 participants
Number of Participants With Serum Chemistry Abnormalities Total Bilirubin GR 1-4 (n=39; n=35)	1 participants	3 participants
Number of Participants With Serum Chemistry Abnormalities Total Bilirubin GR 3-4 (n=39; n=35)	1 participants	0 participants
Number of Participants With Serum Chemistry Abnormalities Creatinine GR 3-4 (n=40; n=36)	0 participants	0 participants

Adverse Events

Ixabepilone 40 mg/m^2

Serious events: 9 serious events

Other events: 40 other events

Deaths: 0 deaths

Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2

Serious events: 12 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

BMS Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ixabepilone 40 mg/m^2 n=40 participants at risk ixabepilone 40 mg/m\^2 every 3 weeks	Cetuximab 250 mg/m^2 + Ixabepilone 40 mg/m^2 n=37 participants at risk cetuximab 400 mg/m\^2 loading dose then 250 mg/m\^2 weekly + ixabepilone 40 mg/m\^2 every 3 weeks
General disorders PYREXIA	5.0% 2/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	0.00% 0/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Gastrointestinal disorders STOMATITIS	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	2.7% 1/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Gastrointestinal disorders VOMITING	2.5% 1/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	2.7% 1/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	2.7% 1/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
General disorders CHEST PAIN	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	2.7% 1/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Vascular disorders THROMBOPHLEBITIS	2.5% 1/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	0.00% 0/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
General disorders FATIGUE	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	2.7% 1/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Gastrointestinal disorders RECTAL HAEMORRHAGE	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	2.7% 1/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
General disorders ASTHENIA	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	2.7% 1/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	2.5% 1/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	0.00% 0/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Vascular disorders HAEMORRHAGE	2.5% 1/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	0.00% 0/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Neoplasms benign, malignant and unspecified (incl cysts and polyps) NEOPLASM MALIGNANT	5.0% 2/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	0.00% 0/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	2.7% 1/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Infections and infestations SKIN INFECTION	2.5% 1/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	0.00% 0/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Respiratory, thoracic and mediastinal disorders HYPOXIA	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	2.7% 1/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
General disorders INFLAMMATION	2.5% 1/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	0.00% 0/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Infections and infestations SEPSIS	2.5% 1/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	0.00% 0/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Cardiac disorders TACHYCARDIA	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	5.4% 2/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	13.5% 5/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Injury, poisoning and procedural complications OVERDOSE	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	2.7% 1/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Cardiac disorders SINUS ARRHYTHMIA	2.5% 1/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	0.00% 0/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Gastrointestinal disorders DIARRHOEA	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	2.7% 1/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTASES TO CENTRAL NERVOUS SYSTEM	2.5% 1/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	0.00% 0/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	2.5% 1/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	0.00% 0/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Blood and lymphatic system disorders FEBRILE NEUTROPENIA	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	5.4% 2/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Blood and lymphatic system disorders NEUTROPENIA	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	5.4% 2/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])
Vascular disorders SUBCLAVIAN VEIN THROMBOSIS	0.00% 0/40 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])	2.7% 1/37 • Assessed from the date of first dose until at least 30 days after the last dose of study drug (Median number of ixabepilone cycles were 5 [range: 1-18 cycles for ixabepilone arm; 1-12 cycles for cetuximab + ixabepilone arm])