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

NCT ID: NCT00140140

Last Updated: 2019-11-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2008-02-29

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.

Conditions

Stage IV (Metastatic) Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

ABI-007

Intervention Type: DRUG

Weekly intravenous infusions over 30 minutes.

vinorelbine

Intervention Type: DRUG

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

Trastuzumab

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

ABI-007

Intervention Type: DRUG

Weekly intravenous infusions over 30 minutes.

vinorelbine

Intervention Type: DRUG

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

Trastuzumab

Intervention Type: DRUG

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.

G-CSF

Intervention Type: BIOLOGICAL

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.

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.

Group Type: EXPERIMENTAL

ABI-007

Intervention Type: DRUG

Weekly intravenous infusions over 30 minutes.

vinorelbine

Intervention Type: DRUG

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

Trastuzumab

Intervention Type: DRUG

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.

G-CSF

Intervention Type: BIOLOGICAL

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.

Interventions

ABI-007

Weekly intravenous infusions over 30 minutes.

Intervention Type: DRUG

vinorelbine

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

Intervention Type: 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.

Intervention Type: DRUG

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Abraxane®; Nab®-Paclitaxel; paclitaxel protein-bound particles for injectable suspension; Navelbine; vinorelbine tartrate; 5'noranhydrovinblastine; Herceptin; granulocyte-colony stimulating factor

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

City of Hope Comprehensive Cancer Care Center

Duarte, California, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Countries

United States

Other Identifiers

CA025

Identifier Type: -

Identifier Source: org_study_id