Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Vinorelbine

Paclitaxel

Albumin-Bound Paclitaxel

Lenograstim

Mitogens

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Adjuvants, Immunologic

Immunologic Factors

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.

Weekly intravenous infusions over 30 minutes.

ABI-007

Weekly intravenous infusions over 10-30 minutes, immediately after ABI-007. Vinorelbine is commercially available and was not supplied by the Sponsor.

vinorelbine

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.

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.

G-CSF

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.

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

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

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.

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.

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

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

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.

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 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.

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.

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.

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.

Celgene

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.

80 mg ABI-007 + 15 mg Vinorelbine

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.

90 mg ABI-007 + 20 mg Vinorelbine

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

< 65 years

>= 65 years

Age, Customized

Sex: Female, Male

Asian

White, Non-Hispanic and Non-Latino

White, Hispanic or Latino

Race/Ethnicity, Customized

Pre-menopausal

Post-menopausal

Menopausal Status

Never Smoked

Current Smoker

Previous Smoker, but have Stopped

Smoking Status

Status 0 (Asymptomatic)

Status 1 (Symptomatic but completely ambulatory)

Status 2 (Ambulatory but unable to work)

Status 3 (Limited self-care)

Status 4 (Completely disabled)

Status 5 (Death)

Eastern Cooperative Oncology Group (ECOG) Performance Status

Associate Director, Clinical Trials Disclosure

Participants With Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0)

Participants With Dose Limiting Toxicities

At least 1 ABI-007 dose reduction

At least 1 Vinorelbine dose reduction

At least 1 ABI-007 dose interruption

At least 1 Vinorelbine dose interruption

At least 1 therapy delay

Percentage of Participants With Discontinued, Delayed or Interrupted Therapy

ANC: grade 0

ANC: grade 1

ANC: grade 2

ANC: grade 3

ANC: grade 4

WBC: grade 0

WBC: grade 1

WBC: grade 2

WBC: grade 3

WBC: grade 4

Platelets: grade 0

Platelets: grade 1

Platelets: grade 2

Platelets: grade 3

Platelets: grade 4

Hemoglobin: grade 0

Hemoglobin: grade 1

Hemoglobin: grade 2

Hemoglobin: grade 3

Hemoglobin: grade 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)

Platelets

Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count

Nadir Measurement for Hemoglobin (Hgb)

Disease control

Complete response

Partial response

Stable disease >=16 weeks

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)

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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