Trial Outcomes & Findings for Trastuzumab, Ixabepilone, and Carboplatin in Treating Patients With HER2/Neu-Positive Metastatic Breast Cancer (NCT NCT00077376)

Last Updated: 2014-05-21

Results Overview

To assess objective response, it is necessary to estimate the overall tumor burden at baseline to which subsequent measurements will be compared. The same method of assessment and the same technique should be used to characterize each lesion at baseline and during follow-up. The best overall response based on RECIST is the best response recorded from registration until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since registration. The best response was determined based on the tumor responses in target and nontarget lesions, with or without new lesions. To be assigned a status of complete or partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 8 weeks.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

61 participants

Primary outcome timeframe

Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

Results posted on

2014-05-21

Participant Flow

The study was activated on March 19th, 2004. Accrual was suspended on December 16th, 2004 after reaching the first stage accrual goal. After a pre-planned toxicity analysis, accrual resumed on March 4th, 2005. The study was completed on March 24th, 2006, after accruing 61 patients.

Participant milestones

Participant milestones
Measure	Trastuzumab/Ixabepilone/Carboplatin During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Overall Study STARTED	61
Overall Study Treated	59
Overall Study HER2+ in Central Testing	39
Overall Study COMPLETED	39
Overall Study NOT COMPLETED	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Trastuzumab/Ixabepilone/Carboplatin During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Overall Study Adverse Event	8
Overall Study Withdrawal by Subject	2
Overall Study Death	1
Overall Study Physician Decision	1
Overall Study Alternative therapy	5
Overall Study Complicating disease	1
Overall Study Still on treatment	1
Overall Study Symptomatic deterioration	1
Overall Study Surgery	1
Overall Study Insurance ran out	1

Baseline Characteristics

Trastuzumab, Ixabepilone, and Carboplatin in Treating Patients With HER2/Neu-Positive Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trastuzumab/Ixabepilone/Carboplatin n=59 Participants During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Age, Continuous	54 years n=5 Participants
Sex: Female, Male Female	59 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

Population: HER2+ patients

Outcome measures

Outcome measures
Measure	Trastuzumab/Ixabepilone/Carboplatin n=39 Participants During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Objective Response for HER2+ Patients (Best Objective Response a Patient Has Ever Experienced on Study) Complete Response	3 Participants
Objective Response for HER2+ Patients (Best Objective Response a Patient Has Ever Experienced on Study) Partial Response	13 Participants
Objective Response for HER2+ Patients (Best Objective Response a Patient Has Ever Experienced on Study) No Change/ Stable	10 Participants
Objective Response for HER2+ Patients (Best Objective Response a Patient Has Ever Experienced on Study) Progression	11 Participants
Objective Response for HER2+ Patients (Best Objective Response a Patient Has Ever Experienced on Study) Unevaluable	2 Participants

SECONDARY outcome

Timeframe: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

Population: All treated patients

Outcome measures

Outcome measures
Measure	Trastuzumab/Ixabepilone/Carboplatin n=59 Participants During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Objective Response for All Treated Patients (the Best Response a Patient Has Ever Experienced on Study) Compelete Response	4 Participants
Objective Response for All Treated Patients (the Best Response a Patient Has Ever Experienced on Study) Partial Response	22 Participants
Objective Response for All Treated Patients (the Best Response a Patient Has Ever Experienced on Study) No Change/ Stable	15 Participants
Objective Response for All Treated Patients (the Best Response a Patient Has Ever Experienced on Study) Progression	16 Participants
Objective Response for All Treated Patients (the Best Response a Patient Has Ever Experienced on Study) Unevaluable	2 Participants

SECONDARY outcome

Timeframe: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

Population: HER2+ patients

This interval will be measured from the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression based on RECIST. Patients progression-free at last follow-up were censored.

Outcome measures

Outcome measures
Measure	Trastuzumab/Ixabepilone/Carboplatin n=39 Participants During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Time to Disease Progression for HER2+ Patients	7.1 Months Interval 5.5 to 9.7

SECONDARY outcome

Timeframe: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

Population: All treated patients

Outcome measures

Outcome measures
Measure	Trastuzumab/Ixabepilone/Carboplatin n=59 Participants During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Time to Disease Progression for All Treated Patients	8.2 Months Interval 6.3 to 9.9

SECONDARY outcome

Timeframe: Assessed every cycle until treatment discontinuation

Population: HER2+ patients

Time from study entry to the date at which a patient was removed from treatment due to progression, toxicity, refusal or death. If a patient was considered to be a major treatment violation or was taken off study as a non-protocol failure, the patient would be censored on the date he/she was removed from treatment.

Outcome measures

Outcome measures
Measure	Trastuzumab/Ixabepilone/Carboplatin n=39 Participants During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Time to Treatment Failure for HER2+ Patients	5.4 Months Interval 5.3 to 6.2

SECONDARY outcome

Timeframe: Assessed every cycle until treatment discontinuation

Population: All treated patients

Outcome measures

Outcome measures
Measure	Trastuzumab/Ixabepilone/Carboplatin n=59 Participants During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Time to Treatment Failure for All Treated Patients	5.9 Months Interval 5.3 to 7.6

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, then every 6 months for 3 years

Population: HER2+ patients

Survival estimate from the Kaplan-Meier curve of the proportion of patients alive at 3 years.

Outcome measures

Outcome measures
Measure	Trastuzumab/Ixabepilone/Carboplatin n=39 Participants During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Kaplan-Meier Estimate of Overall Survival at 3 Years for HER2+ Patients	50 Percentage of Participants Interval 33.3 to 66.0

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, then every 6 months for 3 years

Population: All treated patients

Survival estimate from the Kaplan-Meier curve of the proportion of patients alive at 3 years.

Outcome measures

Outcome measures
Measure	Trastuzumab/Ixabepilone/Carboplatin n=59 Participants During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Kaplan-Meier Estimate of Overall Survival at 3 Years for All Treated Patients	48 Percentage of Participants Interval 34.2 to 61.6

Adverse Events

Trastuzumab/Ixabepilone/Carboplatin

Serious events: 39 serious events

Other events: 59 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Trastuzumab/Ixabepilone/Carboplatin n=59 participants at risk During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Immune system disorders Allergic reaction	3.4% 2/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Blood and lymphatic system disorders Anemia	11.9% 7/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations Leukopenia	32.2% 19/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations Neutropenia	49.2% 29/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations Thrombocytopenia	13.6% 8/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Blood and lymphatic system disorders Hematologic-other	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Vascular disorders Hypertension	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Vascular disorders Hypotension	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
General disorders Fatigue	11.9% 7/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations Weight loss	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
General disorders Death NOS	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Anorexia	5.1% 3/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Dehydration	5.1% 3/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Diarrhea w/o prior colostomy	6.8% 4/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Nausea	6.8% 4/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Vomiting	3.4% 2/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Infections and infestations Infection with Grade 0-2 neutrophils, urinary tract	3.4% 2/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations Alkaline phosphatase increased	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations AST increased	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyperglycemia	3.4% 2/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypokalemia	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypernatremia	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyponatremia	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Nonneuropathic generalized weakness	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Nervous system disorders Encephalopathy	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Nervous system disorders Neuropathy-sensory	6.8% 4/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Nervous system disorders Syncope	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Abdomen, pain	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Extremity-limb, pain	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Joint, pain	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Muscle, pain	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.7% 1/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Vascular disorders Thrombosis/thrombus/embolism	3.4% 2/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.

Other adverse events

Other adverse events
Measure	Trastuzumab/Ixabepilone/Carboplatin n=59 participants at risk During the induction phase, patients were treated with Ixabepilone (BMS-247550) 15mg/m2 intravenously (IV) followed by carboplatin (AUC=2 IV) on days 1, 8 and 15 of a 28-day cycle for a maximum of 6 cycles. Trastuzumab was administered weekly (4mg/kg loading dose then 2mg/kg IV) starting on day 1. Routine premedication included H1 blocker (diphenhydramine 50 mg orally (PO) or IV), H2 blocker (ranitidine 150 mg PO or 50 mg IV or another equivalent H2 blocker), and at least a 5-HT3 antagonist and dexamethasone. After completion of 24 weekly trastuzumab doses (induction therapy), trastuzumab were given at a dose of 6 mg/kg IV every 3 weeks (maintenance therapy) beginning one week after the 24th weekly dose. Trastuzumab were repeated every 21 days until disease progression or prohibitive toxicity.
Immune system disorders Allergic reaction	13.6% 8/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Blood and lymphatic system disorders Anemia	93.2% 55/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations Leukopenia	91.5% 54/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations Neutropenia	74.6% 44/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations Thrombocytopenia	62.7% 37/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Cardiac disorders Left ventricular systolic dysfunction	10.2% 6/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
General disorders Fatigue	86.4% 51/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
General disorders Fever w/o neutropenia	8.5% 5/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Psychiatric disorders Insomnia	11.9% 7/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
General disorders Rigors/chills	5.1% 3/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Sweating	5.1% 3/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations Weight loss	16.9% 10/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Dry skin	6.8% 4/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Alopecia	55.9% 33/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Pruritus/itching	6.8% 4/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Rash/desquamation	16.9% 10/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Vascular disorders Hot flashes	5.1% 3/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Anorexia	37.3% 22/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Constipation	40.7% 24/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Diarrhea w/o prior colostomy	55.9% 33/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Dyspepsia	18.6% 11/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	28.8% 17/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Nausea	71.2% 42/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Nervous system disorders Taste disturbance	35.6% 21/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Vomiting	33.9% 20/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Nose, hemorrhage	8.5% 5/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Infections and infestations Infection with Grade 0-2 neutrophils, skin	5.1% 3/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Infections and infestations Infection with Grade 0-2 neutrophils, urinary tract	5.1% 3/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
General disorders Edema limb	16.9% 10/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypoalbuminemia	5.1% 3/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations Alkaline phosphatase increased	28.8% 17/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations ALT increased	40.7% 24/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations AST increased	33.9% 20/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations Bilirubin increased	6.8% 4/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Investigations Creatinine increased	6.8% 4/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyperglycemia	47.5% 28/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypoglycemia	5.1% 3/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypomagnesemia	5.1% 3/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypokalemia	6.8% 4/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Nervous system disorders Dizziness	11.9% 7/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Psychiatric disorders Anxiety	5.1% 3/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Nervous system disorders Neuropathy-motor	6.8% 4/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Nervous system disorders Neuropathy-sensory	61.0% 36/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Abdomen, pain	10.2% 6/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Back, pain	5.1% 3/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
General disorders Chest/thoracic pain NOS	8.5% 5/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Nervous system disorders Head/headache	13.6% 8/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Joint, pain	23.7% 14/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Muscle, pain	27.1% 16/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Cough	10.2% 6/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	18.6% 11/59 • Assessed every cycle (1 induction cycle = 4 weeks, 1 maintenance cycle = 3 weeks) while on treatment and for 30 days after the end of treatment.

Additional Information

Study Statistician

ECOG Statistical Office

Phone: 617-632-3012

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60