Trial Outcomes & Findings for A Phase I/II Study of ABI-007 (Abraxane®, Nab®-Paclitaxel)and Vinorelbine in Patients With Stage IV (Metastatic) Breast Cancer (NCT NCT00140140)

Last Updated: 2019-11-26

Results Overview

Overall response rate (ORR) is complete response (CR) + partial response (PR). Complete response (CR): The disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. Disappearance of all non-target lesions. The normalization of tumor marker level confirmed at least 4 weeks after initial documentation. Partial response (PR): At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing. As well as persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

16 participants

Primary outcome timeframe

up to month 30

Results posted on

2019-11-26

Participant Flow

Participant milestones

Participant milestones
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Overall Study STARTED	4	6	6
Overall Study COMPLETED	2	4	4
Overall Study NOT COMPLETED	2	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Overall Study Unacceptable toxicity	1	1	2
Overall Study Physician Decision	1	1	0

Baseline Characteristics

A Phase I/II Study of ABI-007 (Abraxane®, Nab®-Paclitaxel)and Vinorelbine in Patients With Stage IV (Metastatic) Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine n=4 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Total n=16 Participants Total of all reporting groups
Age, Customized < 65 years	4 participants 5.74 • n=5 Participants	5 participants 12.60 • n=7 Participants	5 participants 12.23 • n=5 Participants	14 participants n=4 Participants
Age, Customized >= 65 years	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	16 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized White, Non-Hispanic and Non-Latino	3 participants n=5 Participants	5 participants n=7 Participants	4 participants n=5 Participants	12 participants n=4 Participants
Race/Ethnicity, Customized White, Hispanic or Latino	0 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants
Menopausal Status Pre-menopausal	1 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	4 participants n=4 Participants
Menopausal Status Post-menopausal	3 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants	12 participants n=4 Participants
Smoking Status Never Smoked	2 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	9 participants n=4 Participants
Smoking Status Current Smoker	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Smoking Status Previous Smoker, but have Stopped	1 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	5 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Status 0 (Asymptomatic)	1 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	4 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Status 1 (Symptomatic but completely ambulatory)	3 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants	11 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Status 2 (Ambulatory but unable to work)	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Status 3 (Limited self-care)	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Status 4 (Completely disabled)	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Status 5 (Death)	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants

PRIMARY outcome

Timeframe: up to month 30

Population: Treated population

Outcome measures

Outcome measures
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine n=4 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Participants With Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0)	25 percentage of participants Interval 0.6 to 80.6	16.7 percentage of participants Interval 0.4 to 64.1	33.3 percentage of participants Interval 4.3 to 77.7

PRIMARY outcome

Timeframe: up to month 1

Population: Treated population

Toxicities were evaluated based on the U.S. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Any drug-related toxicities CTC Grade 3 or higher were considered dose limiting. Grade 3=severe AE, Grade 4=life-threatening or disabling AE, Grade 5=death. Other conditions considered dose-limiting toxicities include: * requirement of a dose adjustment during the first 4 weeks * a dose delay of \>3 weeks during the first 4 weeks Grade 3 or greater toxicities attributed to the use of Herceptin were not considered dose-limiting toxicities. The optimal tolerated dose of ABI-007 and vinorelbine given concurrently was defined as the dose administered in the absence of DLTs.

Outcome measures

Outcome measures
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine n=4 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Participants With Dose Limiting Toxicities	2 participants	2 participants	2 participants

PRIMARY outcome

Timeframe: up to week 129

Population: Treated population

Percentage of participants who had discontinued therapy or had a delayed dose or an interrupted (omitted) dose due to toxicities/adverse events.

Outcome measures

Outcome measures
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine n=4 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Percentage of Participants With Discontinued, Delayed or Interrupted Therapy At least 1 ABI-007 dose reduction	50 percentage of participants	50 percentage of participants	17 percentage of participants
Percentage of Participants With Discontinued, Delayed or Interrupted Therapy At least 1 Vinorelbine dose reduction	50 percentage of participants	50 percentage of participants	17 percentage of participants
Percentage of Participants With Discontinued, Delayed or Interrupted Therapy At least 1 ABI-007 dose interruption	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With Discontinued, Delayed or Interrupted Therapy At least 1 Vinorelbine dose interruption	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With Discontinued, Delayed or Interrupted Therapy At least 1 therapy delay	75 percentage of participants	83 percentage of participants	67 percentage of participants

PRIMARY outcome

Timeframe: up to week 129 (longest treatment)

Population: Treated population

Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) blood counts were graded using NCI CTCAE version 3. ANC: Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 1.5\*10\^9/L; Grade 2 = \<1.5 - 1.0\*10\^9/L; Grade 3 = \<1.0 - 0.5\*10\^9/L; Grade 4 = \<0.5\*10\^9/L WBC: Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 3.0\*10\^9/L; Grade 2 = \<3.0 - 2.0\*10\^9/L; Grade 3 = \<2.0 - 1.0\*10\^9/L; Grade 4 = \<1.0\*10\^9/L Platelets: Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 75.0\*10\^9/L; Grade 2 = \<75.0 - 50.0\*10\^9/L; Grade 3 = \<50.0 - 25.0\*10\^9/L; Grade 4 = \<25.0\*10\^9/L Hemoglobin: Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 100 g/L ; Grade 2 = \<100 - 80 g/L; Grade 3 = \<80 - 65 g/L; Grade 4 = \<65 g/L

Outcome measures

Outcome measures
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine n=4 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) ANC: grade 0	1 participants	1 participants	3 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) ANC: grade 1	1 participants	1 participants	0 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) ANC: grade 2	0 participants	1 participants	0 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) ANC: grade 3	2 participants	0 participants	1 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) ANC: grade 4	0 participants	3 participants	2 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) WBC: grade 0	2 participants	3 participants	1 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) WBC: grade 1	0 participants	0 participants	1 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) WBC: grade 2	1 participants	1 participants	2 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) WBC: grade 3	1 participants	2 participants	2 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) WBC: grade 4	0 participants	0 participants	0 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) Platelets: grade 0	4 participants	4 participants	6 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) Platelets: grade 1	0 participants	1 participants	0 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) Platelets: grade 2	0 participants	1 participants	0 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) Platelets: grade 3	0 participants	0 participants	0 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) Platelets: grade 4	0 participants	0 participants	0 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) Hemoglobin: grade 0	0 participants	1 participants	0 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) Hemoglobin: grade 1	2 participants	0 participants	0 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) Hemoglobin: grade 2	1 participants	3 participants	4 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) Hemoglobin: grade 3	1 participants	2 participants	2 participants
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3) Hemoglobin: grade 4	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: up to week 129 (longest treatment)

Population: Treated population

Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest observed measurement is the nadir. Blood counts were performed each week of treatment.

Outcome measures

Outcome measures
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine n=4 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count ANC	1.74 10^9/L Standard Deviation 1.444	1.00 10^9/L Standard Deviation 0.864	1.72 10^9/L Standard Deviation 1.589
Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count WBC	2.79 10^9/L Standard Deviation 0.999	2.56 10^9/L Standard Deviation 0.962	2.92 10^9/L Standard Deviation 1.572
Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count Platelets	221.5 10^9/L Standard Deviation 108.19	187.2 10^9/L Standard Deviation 70.35	222.7 10^9/L Standard Deviation 50.11

PRIMARY outcome

Timeframe: up to week 129 (longest treatment)

Population: Treated population

Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest observed measurement is the nadir. Blood counts were performed each week of treatment.

Outcome measures

Outcome measures
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine n=4 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Nadir Measurement for Hemoglobin (Hgb)	89.3 g/L Standard Deviation 16.11	89.7 g/L Standard Deviation 14.53	83.5 g/L Standard Deviation 6.09

SECONDARY outcome

Timeframe: up to month 30

Population: Treated population

Disease control is stable disease (SD) for \>=16 weeks + complete response (CR) + partial response (PR). See Outcome #1 for definitions of CR and PR. RECIST defines SD for target lesions as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.

Outcome measures

Outcome measures
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine n=4 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) Disease control	75 percentage of participants	66.7 percentage of participants	33.3 percentage of participants
Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) Complete response	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) Partial response	25 percentage of participants	17 percentage of participants	33 percentage of participants
Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) Stable disease >=16 weeks	50 percentage of participants	50 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: up to month 30

Population: Treated population of participants with disease progression

Time to progression was defined as the time from the first dose of study drug to the start of progression. Participants that did not have progression were censored at the last known time the patient was evaluated for progression. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.

Outcome measures

Outcome measures
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine n=3 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine n=5 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine n=4 Participants Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Kaplan Meier Estimate for Time to Disease Progression (TTP)	8.8 months Interval 1.0 to 30.4	7.9 months Interval 3.5 to 16.4	4.2 months Interval 3.5 to 14.5

SECONDARY outcome

Timeframe: up to month 30

Population: Treated participants who had a response

Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Patients that did not have progression or have not died were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Complete response (CR) and partial response (PR) are defined in outcome #1. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.

Outcome measures

Outcome measures
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine n=1 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine n=1 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine n=2 Participants Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Kaplan-Meier Estimate for Duration of Response	10.4 months	7.9 months	9.6 months Interval 4.6 to 14.5

SECONDARY outcome

Timeframe: up to month 30

Population: Treated population of participants who had disease progression or who died

PFS was defined as the time from the first dose of study drug to the start of progression or patient death (any cause) whichever occurred first. Participants that did not have progression or have not died were censored at the last known time the participant was progression free. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Because no patients died as a result of a non-disease progression event, the analysis of PFS was identical to the analysis for TTP.

Outcome measures

Outcome measures
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine n=3 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine n=5 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine n=4 Participants Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Kaplan Meier Estimate for Progression-Free Survival (PFS)	8.8 months Interval 1.0 to 30.4	7.9 months Interval 3.5 to 16.4	4.2 months Interval 3.5 to 14.5

SECONDARY outcome

Timeframe: up to 39 months

Population: Treated population

Participant survival is the time from the first dose of study drug to participant death from any cause. Participants that did not die were censored at the last known time the participant was alive.

Outcome measures

Outcome measures
Measure	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine n=4 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine n=6 Participants Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Kaplan-Meier Estimates for Participant Survival	32.7 months Interval 3.1 to 32.7	29.2 months Interval 25.2 to 29.2	22.2 months Interval 19.4 to 26.1

Adverse Events

80 mg ABI-007 + 15 mg Vinorelbine

Serious events: 5 serious events

Other events: 10 other events

Deaths: 0 deaths

90 mg ABI-007 + 20 mg Vinorelbine

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	80 mg ABI-007 + 15 mg Vinorelbine n=10 participants at risk Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants from study Parts 1 and 2 are combined.	90 mg ABI-007 + 20 mg Vinorelbine n=6 participants at risk Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants are from study Part 2.
Blood and lymphatic system disorders Febrile neutropenia	10.0% 1/10 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)	0.00% 0/6 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)
Infections and infestations Bacteraemia	10.0% 1/10 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)	0.00% 0/6 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)
Infections and infestations Catheter related infection	10.0% 1/10 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)	0.00% 0/6 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)
Infections and infestations Cellulitis	10.0% 1/10 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)	0.00% 0/6 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)
Nervous system disorders Cervical myelopathy	10.0% 1/10 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)	0.00% 0/6 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)
Nervous system disorders Facial nerve disorder	10.0% 1/10 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)	0.00% 0/6 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/10 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)	16.7% 1/6 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)
Respiratory, thoracic and mediastinal disorders Hydropneumothorax	10.0% 1/10 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)	0.00% 0/6 • Day 1 - up to 133 weeks (longest treatment plus 4 weeks)

Other adverse events

Additional Information

Associate Director, Clinical Trials Disclosure

Celgene Corporation

Phone: 1-888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Celgene shall complete its review within 30 days after receipt of a proposed publication or presentation submitted by the investigator. Upon request, the publication/presentation might be delayed up to 60 additional days for Celgene to secure intellectual property protection. Subsequent to the multicenter publication or one year after study completion, whichever occurs first, an investigator and/or his/her colleagues may publish the results of INVESTIGATOR's part of the study independently.
Publication restrictions are in place

Restriction type: OTHER