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

• Sponsor: Celgene (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00140140
• Collaborator: (none)
• Enrollment: 16
• Locations: 2
• Arms: 3
• Duration (Months): 30
• Patients Per Site: 8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to: 1) determine the optimal tolerated dose of ABI-007 and vinorelbine, given concurrently on a weekly basis, in the absence of planned growth factor support with granulocyte colony-stimulating factor (G-CSF) (Patients with HER-2/neu positive disease may receive Herceptin, and 2) determine the optimal tolerated dose of ABI-007 and vinorelbine, given concurrently on a weekly basis, in the presence of planned growth factor support with G-CSF.

Condition or Disease	Intervention/Treatment	Phase
Stage IV (Metastatic) Breast Cancer	Drug: ABI-007; Drug: vinorelbine; Drug: Trastuzumab; Biological: G-CSF	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Phase I/II Study of Weekly ABI-007 and Vinorelbine With or Without G-CSF in Patients With Stage IV (Metastatic) Breast Cancer
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: ABI-007; Weekly intravenous infusions over 30 minutes.; Other Names: Abraxane® Nab®-Paclitaxel paclitaxel protein-bound particles for injectable suspension ; Drug: vinorelbine; Weekly intravenous infusions over 10-30 minutes, immediately after ABI-007. Vinorelbine is commercially available and was not supplied by the Sponsor.; Other Names: Navelbine vinorelbine tartrate 5'noranhydrovinblastine ; Drug: Trastuzumab; Trastuzumab was administered to participants who had HER-2-neu positive tumors. Participants received trastuzumab by IV infusion via a vascular access device following dosing with ABI-007 and vinorelbine. During their first cycle, 4 mg/kg was administered on day 1 of that cycle as a loading dose. During subsequent weekly treatments, 2 mg/kg was administered. Trastuzumab is commercially available and was not supplied by the Sponsor.; Other Names: Herceptin
Experimental: 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.	Drug: ABI-007; Weekly intravenous infusions over 30 minutes.; Other Names: Abraxane® Nab®-Paclitaxel paclitaxel protein-bound particles for injectable suspension ; Drug: vinorelbine; Weekly intravenous infusions over 10-30 minutes, immediately after ABI-007. Vinorelbine is commercially available and was not supplied by the Sponsor.; Other Names: Navelbine vinorelbine tartrate 5'noranhydrovinblastine ; Drug: Trastuzumab; Trastuzumab was administered to participants who had HER-2-neu positive tumors. Participants received trastuzumab by IV infusion via a vascular access device following dosing with ABI-007 and vinorelbine. During their first cycle, 4 mg/kg was administered on day 1 of that cycle as a loading dose. During subsequent weekly treatments, 2 mg/kg was administered. Trastuzumab is commercially available and was not supplied by the Sponsor.; Other Names: Herceptin ; Biological: G-CSF; During Part 1, participants followed a dosing regimen with ABI-007 and vinorelbine without G-CSF treatment. However, G-CSF was allowed for administration as necessary in accordance with commonly accepted clinical guidelines. In Part 2, participants started G-CSF treatment in concurrence with their ABI-007 and vinorelbine treatments. G-CSF was administered to all participants on Days 2-7 of each cycle, at a dose of 5 mcg/kg. If the participant's absolute neutrophil (ANC) count was >20,000/mm^3 on the day of anticipated chemotherapy, the site staff reduced the daily dose of G-CSF by 50% to 2.5 mcg/kg. G-CSF is commercially available and was not supplied by the Sponsor.; Other Names: granulocyte-colony stimulating factor
Experimental: 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.	Drug: ABI-007; Weekly intravenous infusions over 30 minutes.; Other Names: Abraxane® Nab®-Paclitaxel paclitaxel protein-bound particles for injectable suspension ; Drug: vinorelbine; Weekly intravenous infusions over 10-30 minutes, immediately after ABI-007. Vinorelbine is commercially available and was not supplied by the Sponsor.; Other Names: Navelbine vinorelbine tartrate 5'noranhydrovinblastine ; Drug: Trastuzumab; Trastuzumab was administered to participants who had HER-2-neu positive tumors. Participants received trastuzumab by IV infusion via a vascular access device following dosing with ABI-007 and vinorelbine. During their first cycle, 4 mg/kg was administered on day 1 of that cycle as a loading dose. During subsequent weekly treatments, 2 mg/kg was administered. Trastuzumab is commercially available and was not supplied by the Sponsor.; Other Names: Herceptin ; Biological: G-CSF; During Part 1, participants followed a dosing regimen with ABI-007 and vinorelbine without G-CSF treatment. However, G-CSF was allowed for administration as necessary in accordance with commonly accepted clinical guidelines. In Part 2, participants started G-CSF treatment in concurrence with their ABI-007 and vinorelbine treatments. G-CSF was administered to all participants on Days 2-7 of each cycle, at a dose of 5 mcg/kg. If the participant's absolute neutrophil (ANC) count was >20,000/mm^3 on the day of anticipated chemotherapy, the site staff reduced the daily dose of G-CSF by 50% to 2.5 mcg/kg. G-CSF is commercially available and was not supplied by the Sponsor.; Other Names: granulocyte-colony stimulating factor

Outcome Measures

Primary Outcome Measures

1. Participants With Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) [up to month 30]

   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.

2. Participants With Dose Limiting Toxicities [up to month 1]

   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.

3. Percentage of Participants With Discontinued, Delayed or Interrupted Therapy [up to week 129]

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

4. 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) [up to week 129 (longest treatment)]

   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

5. Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count [up to week 129 (longest treatment)]

   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.

6. Nadir Measurement for Hemoglobin (Hgb) [up to week 129 (longest treatment)]

   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.

Secondary Outcome Measures

1. 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) [up to month 30]

   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.

2. Kaplan Meier Estimate for Time to Disease Progression (TTP) [up to month 30]

   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.

3. Kaplan-Meier Estimate for Duration of Response [up to month 30]

   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.

4. Kaplan Meier Estimate for Progression-Free Survival (PFS) [up to month 30]

   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.

5. Kaplan-Meier Estimates for Participant Survival [up to 39 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient has microscopically confirmed invasive breast carcinoma with clinical and/or radiographic evidence of stage 4 disease. If diagnosis is based on pleural effusion, positive cytology must be confirmed.

• Patient has had no prior chemotherapy for Stage 4 disease (hormone therapy is permitted). Prior adjuvant paclitaxel by 3-hour infusion is permitted, if there is no residual neuropathy. Prior adjuvant docetaxel on an every 3 week schedule is permitted.

• Disease must be measurable (unidimensional by Response Evaluation Criteria In Solid Tumors (RECIST) criteria) or evaluable (e.g., malignant effusion, marrow involvement). Elevated tumor markers alone are insufficient.

• Age >18.

• Southwest Oncology Group (SWOG)/Eastern Oncology Group (ECOG) performance status must be < or =2 at screen and on treatment day one.

• Life expectancy must be estimated at >16 weeks.

• Prior irradiation is permitted, provided:

• Does not exceed 25% of the estimated bone marrow volume

• Measurable/evaluable disease exists outside the radiation field, or progressive disease is documented within the radiation field.

• Informed consent must be obtained prior to registration.

• Patients must be > 2 weeks from prior surgery; > 3 weeks from radiation therapy to the pelvis, spine or long bones; > 3 weeks from prior chemotherapy (> 6 weeks for mitomycin C or nitrosureas), or > 2 weeks from prior hormonal therapy.

• All patients must have placement of appropriate central venous access device.

• Tumor HER2/neu expression must be determined prior to study enrollment. Assessment may be by fluorescence in situ hybridization (FISH) assay or by immunohistochemistry (ICC). If determination is intermediate by ICC, FISH must be performed. For enrollment purposes, this phase I study will not discriminate based on HER2 status. However, documentation of patients' HER2 status will be maintained and Herceptin will be prescribed for all HER2 positive patients.

Exclusion Criteria:

• Granulocytes < 1,500/mm^3.

• Platelets < 100,000/mm^3.

• Hemoglobin < 9 gm/dl.

• Creatinine > 2.0 mg/dl.

• Total bilirubin > 2 mg/dl.

• Visceral crisis characterized by rapidly progressive hepatic or lymphangitic lung metastases.

• Medically unstable as judged by the patient's physician.

• Pregnancy or lactation; failure to employ adequate contraception.

• Uncontrolled central nervous system (CNS) disease.

• Pre-existing Grade ≥ 2 peripheral neuropathy except for abnormalities due to cancer.

• Psychological, familial, sociological or geographical conditions which do not permit weekly medical follow-up and compliance with the study protocol.

• Prior therapy with vinorelbine or prior therapy with a taxane that resulted in neuropathy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Care Center	Duarte	California	United States	91010
2	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Celgene

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT00140140
• Other Study ID Numbers: CA025
• First Posted: Sep 1, 2005
• Last Update Posted: Nov 26, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Celgene: Breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Vinorelbine; Albumin-Bound Paclitaxel; Trastuzumab; Lenograstim

Study Results

Participant Flow

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	4	6	6
COMPLETED	2	4	4
NOT COMPLETED	2	2	2

Baseline Characteristics

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine	Total
Arm/Group Description	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.	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.	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 of all reporting groups
Overall Participants	4	6	6	16
Age, Customized (participants) [Number]
< 65 years	4 (5.74) 100%	5 (12.60) 83.3%	5 (12.23) 83.3%	14 87.5%
>= 65 years	0 0%	1 16.7%	1 16.7%	2 12.5%
Sex: Female, Male (Count of Participants)
Female	4 100%	6 100%	6 100%	16 100%
Male	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Asian	1 25%	0 0%	0 0%	1 6.3%
White, Non-Hispanic and Non-Latino	3 75%	5 83.3%	4 66.7%	12 75%
White, Hispanic or Latino	0 0%	1 16.7%	2 33.3%	3 18.8%
Menopausal Status (participants) [Number]
Pre-menopausal	1 25%	2 33.3%	1 16.7%	4 25%
Post-menopausal	3 75%	4 66.7%	5 83.3%	12 75%
Smoking Status (participants) [Number]
Never Smoked	2 50%	4 66.7%	3 50%	9 56.3%
Current Smoker	1 25%	1 16.7%	0 0%	2 12.5%
Previous Smoker, but have Stopped	1 25%	1 16.7%	3 50%	5 31.3%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
Status 0 (Asymptomatic)	1 25%	2 33.3%	1 16.7%	4 25%
Status 1 (Symptomatic but completely ambulatory)	3 75%	4 66.7%	4 66.7%	11 68.8%
Status 2 (Ambulatory but unable to work)	0 0%	0 0%	1 16.7%	1 6.3%
Status 3 (Limited self-care)	0 0%	0 0%	0 0%	0 0%
Status 4 (Completely disabled)	0 0%	0 0%	0 0%	0 0%
Status 5 (Death)	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Participants With Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0)
Description	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.
Time Frame	up to month 30

Outcome Measure Data

Analysis Population Description

Treated population

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.	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.	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.
Measure Participants	4	6	6
Number (95% Confidence Interval) [percentage of participants]	25 625%	16.7 278.3%	33.3 555%

2. Primary Outcome

Title	Participants With Dose Limiting Toxicities
Description	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.
Time Frame	up to month 1

Outcome Measure Data

Analysis Population Description

Treated population

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.	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.	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.
Measure Participants	4	6	6
Number [participants]	2 50%	2 33.3%	2 33.3%

3. Primary Outcome

Title	Percentage of Participants With Discontinued, Delayed or Interrupted Therapy
Description	Percentage of participants who had discontinued therapy or had a delayed dose or an interrupted (omitted) dose due to toxicities/adverse events.
Time Frame	up to week 129

Outcome Measure Data

Analysis Population Description

Treated population

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.	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.	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.
Measure Participants	4	6	6
At least 1 ABI-007 dose reduction	50 1250%	50 833.3%	17 283.3%
At least 1 Vinorelbine dose reduction	50 1250%	50 833.3%	17 283.3%
At least 1 ABI-007 dose interruption	0 0%	0 0%	0 0%
At least 1 Vinorelbine dose interruption	0 0%	0 0%	0 0%
At least 1 therapy delay	75 1875%	83 1383.3%	67 1116.7%

4. Primary Outcome

Title	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)
Description	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
Time Frame	up to week 129 (longest treatment)

Outcome Measure Data

Analysis Population Description

Treated population

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.	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.	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.
Measure Participants	4	6	6
ANC: grade 0	1 25%	1 16.7%	3 50%
ANC: grade 1	1 25%	1 16.7%	0 0%
ANC: grade 2	0 0%	1 16.7%	0 0%
ANC: grade 3	2 50%	0 0%	1 16.7%
ANC: grade 4	0 0%	3 50%	2 33.3%
WBC: grade 0	2 50%	3 50%	1 16.7%
WBC: grade 1	0 0%	0 0%	1 16.7%
WBC: grade 2	1 25%	1 16.7%	2 33.3%
WBC: grade 3	1 25%	2 33.3%	2 33.3%
WBC: grade 4	0 0%	0 0%	0 0%
Platelets: grade 0	4 100%	4 66.7%	6 100%
Platelets: grade 1	0 0%	1 16.7%	0 0%
Platelets: grade 2	0 0%	1 16.7%	0 0%
Platelets: grade 3	0 0%	0 0%	0 0%
Platelets: grade 4	0 0%	0 0%	0 0%
Hemoglobin: grade 0	0 0%	1 16.7%	0 0%
Hemoglobin: grade 1	2 50%	0 0%	0 0%
Hemoglobin: grade 2	1 25%	3 50%	4 66.7%
Hemoglobin: grade 3	1 25%	2 33.3%	2 33.3%
Hemoglobin: grade 4	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count
Description	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.
Time Frame	up to week 129 (longest treatment)

Outcome Measure Data

Analysis Population Description

Treated population

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.	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.	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.
Measure Participants	4	6	6
ANC	1.74 (1.444)	1.00 (0.864)	1.72 (1.589)
WBC	2.79 (0.999)	2.56 (0.962)	2.92 (1.572)
Platelets	221.5 (108.19)	187.2 (70.35)	222.7 (50.11)

6. Primary Outcome

Title	Nadir Measurement for Hemoglobin (Hgb)
Description	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.
Time Frame	up to week 129 (longest treatment)

Outcome Measure Data

Analysis Population Description

Treated population

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.	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.	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.
Measure Participants	4	6	6
Mean (Standard Deviation) [g/L]	89.3 (16.11)	89.7 (14.53)	83.5 (6.09)

7. Secondary Outcome

Title	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)
Description	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.
Time Frame	up to month 30

Outcome Measure Data

Analysis Population Description

Treated population

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.	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.	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.
Measure Participants	4	6	6
Disease control	75 1875%	66.7 1111.7%	33.3 555%
Complete response	0 0%	0 0%	0 0%
Partial response	25 625%	17 283.3%	33 550%
Stable disease >=16 weeks	50 1250%	50 833.3%	0 0%

8. Secondary Outcome

Title	Kaplan Meier Estimate for Time to Disease Progression (TTP)
Description	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.
Time Frame	up to month 30

Outcome Measure Data

Analysis Population Description

Treated population of participants with disease progression

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.	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.	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.
Measure Participants	3	5	4
Median (95% Confidence Interval) [months]	8.8	7.9	4.2

9. Secondary Outcome

Title	Kaplan-Meier Estimate for Duration of Response
Description	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.
Time Frame	up to month 30

Outcome Measure Data

Analysis Population Description

Treated participants who had a response

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.	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.	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.
Measure Participants	1	1	2
Median (95% Confidence Interval) [months]	10.4	7.9	9.6

10. Secondary Outcome

Title	Kaplan Meier Estimate for Progression-Free Survival (PFS)
Description	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.
Time Frame	up to month 30

Outcome Measure Data

Analysis Population Description

Treated population of participants who had disease progression or who died

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.	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.	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.
Measure Participants	3	5	4
Median (95% Confidence Interval) [months]	8.8	7.9	4.2

11. Secondary Outcome

Title	Kaplan-Meier Estimates for Participant Survival
Description	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.
Time Frame	up to 39 months

Outcome Measure Data

Analysis Population Description

Treated population

Arm/Group Title	Part 1: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 80 mg ABI-007 + 15 mg Vinorelbine	Part 2: 90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.	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.	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.
Measure Participants	4	6	6
Median (95% Confidence Interval) [months]	32.7	29.2	22.2

Adverse Events

Time Frame	Day 1 - up to 133 weeks (longest treatment plus 4 weeks)
Arm/Group Title	80 mg ABI-007 + 15 mg Vinorelbine		90 mg ABI-007 + 20 mg Vinorelbine
Arm/Group Description	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.		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.
All Cause Mortality
	80 mg ABI-007 + 15 mg Vinorelbine		90 mg ABI-007 + 20 mg Vinorelbine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	80 mg ABI-007 + 15 mg Vinorelbine		90 mg ABI-007 + 20 mg Vinorelbine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/10 (50%)		1/6 (16.7%)
Blood and lymphatic system disorders
Febrile neutropenia	1/10 (10%)		0/6 (0%)
Infections and infestations
Bacteraemia	1/10 (10%)		0/6 (0%)
Catheter related infection	1/10 (10%)		0/6 (0%)
Cellulitis	1/10 (10%)		0/6 (0%)
Nervous system disorders
Cervical myelopathy	1/10 (10%)		0/6 (0%)
Facial nerve disorder	1/10 (10%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/10 (0%)		1/6 (16.7%)
Hydropneumothorax	1/10 (10%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	80 mg ABI-007 + 15 mg Vinorelbine		90 mg ABI-007 + 20 mg Vinorelbine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/10 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Anemia	8/10 (80%)		6/6 (100%)
Haemolysis	1/10 (10%)		0/6 (0%)
Leukocytosis	1/10 (10%)		1/6 (16.7%)
Lymphopenia	5/10 (50%)		2/6 (33.3%)
Neutropenia	3/10 (30%)		1/6 (16.7%)
Cardiac disorders
Palpitations	1/10 (10%)		0/6 (0%)
Tachycardia	5/10 (50%)		0/6 (0%)
Ear and labyrinth disorders
Vertigo	0/10 (0%)		1/6 (16.7%)
Eye disorders
Keratoconjunctivitis sicca	3/10 (30%)		0/6 (0%)
Lacrimation increased	4/10 (40%)		1/6 (16.7%)
Vision blurred	2/10 (20%)		0/6 (0%)
Visual acuity reduced	2/10 (20%)		0/6 (0%)
Gastrointestinal disorders
Abdominal pain	1/10 (10%)		0/6 (0%)
Chapped lips	1/10 (10%)		0/6 (0%)
Constipation	3/10 (30%)		1/6 (16.7%)
Diarrhoea	4/10 (40%)		1/6 (16.7%)
Dry mouth	0/10 (0%)		1/6 (16.7%)
Gastrooesophageal reflux disease	0/10 (0%)		1/6 (16.7%)
Hypoaesthesia oral	1/10 (10%)		0/6 (0%)
Nausea	3/10 (30%)		2/6 (33.3%)
Oral mucosal blistering	1/10 (10%)		0/6 (0%)
Post procedural nausea	1/10 (10%)		0/6 (0%)
Tooth disorder	1/10 (10%)		0/6 (0%)
Toothache	2/10 (20%)		0/6 (0%)
General disorders
Asthenia	1/10 (10%)		0/6 (0%)
Catheter related complication	0/10 (0%)		1/6 (16.7%)
Catheter site erythema	0/10 (0%)		1/6 (16.7%)
Catheter site rash	0/10 (0%)		1/6 (16.7%)
Chest pain	2/10 (20%)		0/6 (0%)
Fatigue	8/10 (80%)		5/6 (83.3%)
Gait abnormal	1/10 (10%)		1/6 (16.7%)
Mucosal inflammation	1/10 (10%)		0/6 (0%)
Oedema mucosal	1/10 (10%)		0/6 (0%)
Oedema peripheral	2/10 (20%)		2/6 (33.3%)
Pain	4/10 (40%)		1/6 (16.7%)
Pyrexia	4/10 (40%)		2/6 (33.3%)
Rigors	2/10 (20%)		0/6 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/10 (10%)		0/6 (0%)
Infections and infestations
Bronchitis	2/10 (20%)		0/6 (0%)
Folliculitis	1/10 (10%)		0/6 (0%)
Furuncle	0/10 (0%)		1/6 (16.7%)
Herpes simplex	1/10 (10%)		0/6 (0%)
Infusion site infection	1/10 (10%)		0/6 (0%)
Nasopharyngitis	1/10 (10%)		0/6 (0%)
Onychomycosis	1/10 (10%)		0/6 (0%)
Pneumonia	0/10 (0%)		1/6 (16.7%)
Upper respiratory tract infection	2/10 (20%)		0/6 (0%)
Urinary tract infection	3/10 (30%)		0/6 (0%)
Injury, poisoning and procedural complications
Blister	1/10 (10%)		0/6 (0%)
Contusion	1/10 (10%)		1/6 (16.7%)
Device failure	1/10 (10%)		0/6 (0%)
Hepatic trauma	1/10 (10%)		0/6 (0%)
Investigations
Alanine aminotransferase	1/10 (10%)		0/6 (0%)
Alanine aminotransferase increased	4/10 (40%)		3/6 (50%)
Aspartate aminotransferase	1/10 (10%)		0/6 (0%)
Aspartate aminotransferase increased	7/10 (70%)		4/6 (66.7%)
Blood albumin decreased	0/10 (0%)		1/6 (16.7%)
Blood alkaline phosphatase	1/10 (10%)		0/6 (0%)
Blood alkaline phosphatase increased	5/10 (50%)		4/6 (66.7%)
Blood calcium decreased	2/10 (20%)		1/6 (16.7%)
Blood chloride increased	1/10 (10%)		0/6 (0%)
Blood glucose increased	1/10 (10%)		0/6 (0%)
Blood potassium decreased	1/10 (10%)		0/6 (0%)
Cardiac murmur	1/10 (10%)		0/6 (0%)
Haematocrit	1/10 (10%)		0/6 (0%)
Haematocrit decreased	2/10 (20%)		1/6 (16.7%)
Haemoglobin decreased	3/10 (30%)		1/6 (16.7%)
Iron binding capacity total decreased	1/10 (10%)		0/6 (0%)
Lymphocyte count decreased	2/10 (20%)		2/6 (33.3%)
Neutrophil count decreased	6/10 (60%)		2/6 (33.3%)
Platelet count decreased	2/10 (20%)		0/6 (0%)
Protein total decreased	0/10 (0%)		1/6 (16.7%)
Prothrombin time prolonged	1/10 (10%)		0/6 (0%)
Red blood cell count decreased	1/10 (10%)		1/6 (16.7%)
Weight decreased	3/10 (30%)		1/6 (16.7%)
White blood cell count decreased	8/10 (80%)		3/6 (50%)
Metabolism and nutrition disorders
Anorexia	1/10 (10%)		2/6 (33.3%)
Hyperglycaemia	5/10 (50%)		3/6 (50%)
Hyperuricaemia	1/10 (10%)		2/6 (33.3%)
Hypoalbuminaemia	8/10 (80%)		2/6 (33.3%)
Hypocalcaemia	7/10 (70%)		2/6 (33.3%)
Hypokalaemia	7/10 (70%)		2/6 (33.3%)
Hypomagnesaemia	3/10 (30%)		0/6 (0%)
Hyponatraemia	1/10 (10%)		1/6 (16.7%)
Hypophosphataemia	3/10 (30%)		3/6 (50%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/10 (40%)		0/6 (0%)
Back pain	4/10 (40%)		0/6 (0%)
Bone pain	3/10 (30%)		1/6 (16.7%)
Facial pain	1/10 (10%)		0/6 (0%)
Muscular weakness	1/10 (10%)		1/6 (16.7%)
Musculoskeletal stiffness	1/10 (10%)		0/6 (0%)
Myalgia	3/10 (30%)		0/6 (0%)
Pain in extremity	1/10 (10%)		0/6 (0%)
Sacral pain	1/10 (10%)		0/6 (0%)
Nervous system disorders
Dizziness	1/10 (10%)		0/6 (0%)
Dysgeusia	1/10 (10%)		0/6 (0%)
Headache	3/10 (30%)		1/6 (16.7%)
Hypoaesthesia	4/10 (40%)		1/6 (16.7%)
Memory impairment	1/10 (10%)		0/6 (0%)
Neuropathy	1/10 (10%)		1/6 (16.7%)
Neuropathy peripheral	2/10 (20%)		1/6 (16.7%)
Paraesthesia	1/10 (10%)		0/6 (0%)
Peripheral sensory neuropathy	1/10 (10%)		0/6 (0%)
Syncope	1/10 (10%)		0/6 (0%)
Psychiatric disorders
Anxiety	2/10 (20%)		1/6 (16.7%)
Depression	1/10 (10%)		0/6 (0%)
Insomnia	2/10 (20%)		1/6 (16.7%)
Restlessness	0/10 (0%)		1/6 (16.7%)
Renal and urinary disorders
Haematuria	2/10 (20%)		0/6 (0%)
Pollakiuria	0/10 (0%)		1/6 (16.7%)
Proteinuria	3/10 (30%)		0/6 (0%)
Renal pain	1/10 (10%)		0/6 (0%)
Urinary hesitation	1/10 (10%)		0/6 (0%)
Urinary retention	1/10 (10%)		0/6 (0%)
Reproductive system and breast disorders
Amenorrhoea	1/10 (10%)		0/6 (0%)
Breast pain	1/10 (10%)		0/6 (0%)
Pelvic pain	1/10 (10%)		0/6 (0%)
Vaginal haemorrhage	1/10 (10%)		0/6 (0%)
Vaginal pain	0/10 (0%)		1/6 (16.7%)
Vulvovaginal dryness	0/10 (0%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Cough	4/10 (40%)		3/6 (50%)
Dry throat	1/10 (10%)		0/6 (0%)
Dyspnoea	3/10 (30%)		2/6 (33.3%)
Epistaxis	2/10 (20%)		1/6 (16.7%)
Hoarseness	3/10 (30%)		1/6 (16.7%)
Hypoxia	1/10 (10%)		1/6 (16.7%)
Lung infiltration	1/10 (10%)		0/6 (0%)
Nasal congestion	1/10 (10%)		2/6 (33.3%)
Pharyngeal erythema	1/10 (10%)		0/6 (0%)
Pharyngolaryngeal pain	3/10 (30%)		0/6 (0%)
Pleural effusion	1/10 (10%)		0/6 (0%)
Postnasal drip	1/10 (10%)		0/6 (0%)
Respiratory tract congestion	1/10 (10%)		0/6 (0%)
Rhinitis	1/10 (10%)		0/6 (0%)
Rhinorrhoea	2/10 (20%)		0/6 (0%)
Sinus congestion	1/10 (10%)		0/6 (0%)
Throat irritation	0/10 (0%)		1/6 (16.7%)
Skin and subcutaneous tissue disorders
Acne	0/10 (0%)		1/6 (16.7%)
Alopecia	5/10 (50%)		5/6 (83.3%)
Dermatitis	1/10 (10%)		0/6 (0%)
Dry skin	2/10 (20%)		1/6 (16.7%)
Erythema	1/10 (10%)		1/6 (16.7%)
Nail discolouration	0/10 (0%)		1/6 (16.7%)
Nail disorder	0/10 (0%)		1/6 (16.7%)
Night sweats	1/10 (10%)		0/6 (0%)
Palmar-plantar erythrodysaesthesia	1/10 (10%)		0/6 (0%)
Photosensitivity reaction	1/10 (10%)		0/6 (0%)
Pruritus	3/10 (30%)		1/6 (16.7%)
Rash	6/10 (60%)		4/6 (66.7%)
Rash generalised	1/10 (10%)		0/6 (0%)
Skin discolouration	2/10 (20%)		0/6 (0%)
Skin disorder	1/10 (10%)		0/6 (0%)
Skin lesion	0/10 (0%)		1/6 (16.7%)
Skin tightness	1/10 (10%)		0/6 (0%)
Urticaria	1/10 (10%)		0/6 (0%)
Vascular disorders
Flushing	1/10 (10%)		0/6 (0%)
Hot flush	2/10 (20%)		0/6 (0%)
Hypotension	2/10 (20%)		1/6 (16.7%)
Lymphoedema	0/10 (0%)		2/6 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.