Paclitaxel Albumin-Stabilized Nanoparticle Formulation, Bevacizumab, and Gemcitabine as First-Line Therapy in Treating Patients With Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00503906
First received: July 17, 2007
Last updated: August 13, 2013
Last verified: August 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving paclitaxel albumin-stabilized nanoparticle formulation together with bevacizumab and gemcitabine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving paclitaxel albumin-stabilized nanoparticle formulation together with bevacizumab and gemcitabine works as first-line therapy in treating patients with metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: Bevacizumab
Drug: Gemcitabine
Drug: Abraxane
Genetic: Analysis of SPARC Expression
Other: Circulating Tumor Cells (CTC) Analysis
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Abraxane, Bevacizumab and Gemcitabine for First Line Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by University of Miami Sylvester Comprehensive Cancer Center:

Primary Outcome Measures:
  • Progression-free Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Progression-free survival will be measured from the first dose date to the earliest date of documented evidence of progressive disease or the date of death due to any causes, whichever occurs first.


Secondary Outcome Measures:
  • Percentage of Subjects Achieving 6 Month Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The percentage of subjects achieving 6 month survival, the time from date of initial Gemcitabine, Abraxane and Bevacizumab therapy to date of death. In the absence of confirmation of death, survival time will be censored to last date of follow-up

  • Percentage of Subjects Achieving 12 Month Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Percentage of subjects achieving 12 month survival,the time from date of initial Gemcitabine, Abraxane and Bevacizumab therapy to date of death. In the absence of confirmation of death, survival time will be censored to last date of follow-up12 month survival

  • Percentage of Subjects Achieving 18 Month Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Percentage of subjects achieving 18 month survival, the time from date of initial Gemcitabine, Abraxane and Bevacizumab therapy to date of death. In the absence of confirmation of death, survival time will be censored to last date of follow-up

  • Percentage of Subjects Achieving 24 Months Survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Percentage of subjects achieving 24 month survival, the time from date of initial Gemcitabine, Abraxane and Bevacizumab therapy to date of death. In the absence of confirmation of death, survival time will be censored to last date of follow-up12 month survival

  • Relationship Between Circulating Tumor Cells (CTC) and Disease Progression as Measured by Presence of CTC at Baseline and Over the Course of Study Treatment [ Time Frame: Baseline, over the course of Treatment ] [ Designated as safety issue: No ]
  • To Determine Safety and Side Effect Profile of the Treatment Combination. [ Time Frame: Over the course of study treatment. ] [ Designated as safety issue: Yes ]
    The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for adverse event reporting.


Enrollment: 30
Study Start Date: June 2007
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abraxane, Bevacizumab and Gemcitabine Drug: Bevacizumab
Bevacizumab 10 mg/kg BW IV over 30 minutes (+/- 5 minutes). One cycle is 28 days with chemotherapy Gemcitabine, Abraxane® and Bevacizumab given on day 1 and 15 of each treatment cycle.
Drug: Gemcitabine
Gemcitabine 1500 mg/m2 BSA IV over 30 minutes (+/- 5 minutes). One cycle is 28 days with chemotherapy Gemcitabine, Abraxane® and Bevacizumab given on day 1 and 15 of each treatment cycle.
Other Name: Gemzar
Drug: Abraxane
Abraxane® 150 mg/m2 IV over 30 minutes (+/- 5 minutes). One cycle is 28 days with chemotherapy Gemcitabine, Abraxane® and Bevacizumab given on day 1 and 15 of each treatment cycle.
Other Name: Albumin-Bound Paclitaxel Formulation
Genetic: Analysis of SPARC Expression
A sample of tumor block will be sent to Abraxis Bioscience for analysis of SPARC expression, at a time and location to be determined by the Principal Investigator
Other: Circulating Tumor Cells (CTC) Analysis
CTC will be measured in peripheral blood, as reference to the CellSearch System. Samples will be drawn within 48 hours of the day # 1 infusion for first cycle and again within 48 hours of the day #1 infusion for every other cycle (i.e. every odd cycle).

Detailed Description:

OBJECTIVES:

Primary

  • To determine preliminary evidence of efficacy of the combination regimen of gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation (Abraxane®), and bevacizumab as first-line treatment for Her2/neu-negative metastatic (stage IV) breast cancer.

Secondary

  • To determine the partial, complete, and overall response rate.
  • To determine the safety and side effect profile of the treatment combination.
  • To explore the relationship between circulating tumor cells (CTC) and disease progression, by measuring CTC at baseline and over the course of treatment.

OUTLINE: Patients receive gemcitabine hydrochloride IV over 30 minutes followed by paclitaxel albumin-stabilized nanoparticle formulation (Abraxane®) IV over 30 minutes followed by bevacizumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor tissue and blood sample collection periodically for correlative laboratory studies. Tumor tissue samples are analyzed for secreted protein acidic rich in cysteine (SPARC) expression by antibody immunostaining. Blood samples are analyzed for the presence of circulating tumor cells by the CellSearch™ system.

After completion of study treatment, patients are followed at 1 year and then annually thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Patients must meet 1 of the following criteria:

    • Treatment-naïve with newly diagnosed Her2/neu non-overexpressing (non amplified) metastatic (stage IV) breast cancer
    • HER2/neu-negative breast cancer with metastasis diagnosed 6 or more months after completing primary systemic treatment (i.e., neoadjuvant or adjuvant chemotherapy)
  • Measurable disease as defined by RECIST criteria OR evaluable disease
  • No CNS or brain metastases

PATIENT CHARACTERISTICS:

  • Inclusion Criteria

    • Pre- or postmenopausal
    • ECOG performance status 0-1
    • Life expectancy > 3 months
    • Female or male patients must be surgically sterilized or willing to use an acceptable method of birth control for the duration of the study
    • Neutrophils ≥ 1.5 x 10^9/L
    • Platelets ≥ 100 x 10^9/L
    • Hemoglobin ≥ 9.0 g/dL
    • Serum creatinine ≤ 1.5 mg/dL
    • Bilirubin ≤ upper limit of normal (ULN), except when caused by metastatic disease
    • ALT/AST ≤ 2.5 times ULN, except when caused by metastatic disease
    • Urine protein:creatinine (UPC) ratio < 1.0 at screening
  • Exclusion Criteria

    • Pregnant (positive pregnancy test) or lactating
    • History of gastrointestinal bleeding within the past 3 months
    • Inadequately controlled hypertension (i.e., systolic BP > 150 mm Hg and/or diastolic BP > 100 mm Hg while on antihypertensive medications)
    • Prior history of hypertensive crisis or hypertensive encephalopathy
    • Peripheral neuropathy > grade 1
    • Clinical AIDS or known positive HIV serology
    • No concurrent clinically evident malignancy except for inactive nonmelanoma skin cancer, inactive cervical cancer, or other cancer for which the patient has been disease-free for 5 years
    • Unstable angina
    • New York Heart Association class II-IV congestive heart failure
    • History of myocardial infarction within the past 6 months
    • History of stroke within the past 6 months
    • Clinically significant peripheral vascular disease
    • Evidence of bleeding diathesis or coagulopathy
    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
    • Serious nonhealing wound, ulcer, or bone fracture
    • Serious medical or psychiatric illness that would render chemotherapy unsafe
    • Significant traumatic injury within the past 28 days

PRIOR CONCURRENT THERAPY:

  • Exclusion Criteria

    • Previous chemotherapy for metastatic breast cancer
    • Previous treatment with gemcitabine hydrochloride
    • Chemotherapy within 4 weeks prior to study enrollment
    • Radiation therapy or evidence of acute effects of radiation therapy within 2 weeks prior to study enrollment
    • Any major surgery or open biopsy within 4 weeks prior to study enrollment
    • Minor surgical procedures (i.e., fine needle aspirations or core biopsies) within 7 days prior to study enrollment
    • Participation in another experimental drug study (other than a bevacizumab clinical trial for cancer) within 4 weeks prior to study enrollment
    • Anticipation of need for major surgical procedure during the course of the study
    • Concurrent irradiation
    • Other concurrent chemotherapy, immunotherapy, or anti-tumor hormonal therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00503906

Locations
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami Sylvester Comprehensive Cancer Center
Investigators
Study Chair: Stefan Gluck, MD, PhD, FRCPC University of Miami Sylvester Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00503906     History of Changes
Other Study ID Numbers: UMIAMI-20060913, SCCC-2006081
Study First Received: July 17, 2007
Results First Received: January 22, 2013
Last Updated: August 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami Sylvester Comprehensive Cancer Center:
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Bevacizumab
Paclitaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014