Phase 2 Study of Gemzar, Taxol & Avastin Combination as 1st Line Treatment for Metastatic Breast Cancer

This study has been completed.
Sponsor:
Collaborators:
Genentech
Eli Lilly and Company
Information provided by (Responsible Party):
George Albert Fisher, Stanford University
ClinicalTrials.gov Identifier:
NCT00403130
First received: November 22, 2006
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

Given the lack of other viable treatment options for metastatic neuroendocrine tumors, contrasted with our positive anecdotal experience, and the relative tolerability of the treatment regimen for colorectal cancer patients, we propose a single-institution phase II trial investigating the efficacy of capecitabine, oxaliplatin and bevacizumab for patients with metastatic neuroendocrine tumors.


Condition Intervention Phase
Breast Cancer
Metastatic Breast Cancer
Drug: Gemcitabine
Drug: Paclitaxel
Drug: Bevacizumab
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Time to progression will be the primary outcome measure for this trial. [ Time Frame: At point of disease progression ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival and response rates will be secondary outcome measures. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • toxicity data will be collected for a comprehensive safety analysis of this regimen in this patient population. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 26
Study Start Date: February 2006
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase II 3-drug regimen
Gemcitabine + Paclitaxel + Bevacizumab
Drug: Gemcitabine
Gemcitabine 1000 mg/m2 by IV infusion, days 1, 8, and 15 in 28-day cycles
Other Name: Gemzar
Drug: Paclitaxel
Paclitaxel 80 mg/m2 by IV infusion, days 1, 8, and 15 in 28-day cycles
Other Name: Taxol
Drug: Bevacizumab
Bevacizumab 10 mg/kg by IV infusion, days 1 and 15 in 28-day cycles
Other Name: Avastin

Detailed Description:

This study will evaluate the efficacy by estimation of time to progression of Bevacizumab in combination with Paclitaxel and Gemcitabine, as concurrent use of these two agents alone, was shown to increase overall survival, time to progression, and response rate in previously untreated metastatic breast cancer. The improvement in overall survival was based on an interim analysis. It is hypothesized that this three-drug regimen will result in increased time to progression and possibly higher response rates in the current study population. Moreover, it is believed that this regimen will be well tolerated with minimal overlapping toxicities.

  Eligibility

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

Inclusion Criteria:- Patients must have previously untreated metastatic breast cancer.

  • Patients may have had prior chest wall irradiation or palliative radiation to bony sites for control of pain or fracture. These sites of disease, however, will not be considered as sites of measurable disease.
  • Use of bisphosphonates will be permitted.
  • Patients must have an ECoG performance status of 0 or 1.
  • Patients must have adequate hepatic, renal and bone marrow function as defined by the following:

    • granulocyte count >= 1500/mm^3
    • platelet count >= 100,000/mm^3
    • hemoglobin >=8.0 g/dl.
    • SGoT/SGPT <= 2.5X the institutional upper limit of normal (ULN) if alkaline phosphatase is d ULN or alkaline phosphatase may be up to 4X ULN if transaminases are d ULN.
    • total bilirubin within institutional limits of normal.
    • calculated creatinine clearance >= 30 ml/min using the formula: a. Ccr(ml/min) = ((140-age in years) X (wt in kg) X 0.85 (females))/(72 X Serum creatinine in mg/dl)
  • All patients must be >= 18 years of age.
  • Patients with prior anthracyclines in the adjuvant setting or prior chest wall radiation must have left ventricular ejection fraction (LVEF) within the institutional range of normal as assessed by pretreatment MUGA scan or ECHo.
  • All patients must give signed written informed consent. o Patients may have received adjuvant therapy as long as therapy complete >12 months from study entry.

Exclusion Criteria:- Patients on hormonal therapy

  • Patients had prior treatment for metastatic disease with cytotoxic agents or inhibitors of EGFR.
  • Her2NEU positive breast cancers, either IHC 3+ or FISH +.
  • Patients who are pregnant/lactating. Patients of childbearing potential must have a negative pregnancy test taken <= 2 weeks prior to study enrollment. Patients of childbearing potential must consent to the use of effective contraception during the study period and for six months thereafter.
  • Patients have had active malignancies other than breast cancer in the past 5 years with the exception of in situ carcinoma of the cervix or nonmelanomatous skin cancer.
  • Patients have active or unresolved infection.
  • Patients with pre-existing peripheral neuropathy > Grade 1.
  • Patients with a prior history of severe hypersensitivity reaction to paclitaxel, gemcitabine, bevacizumab or drugs formulated with polysorbate 80.
  • Patients ineligible due to Bevacizumab-specific concerns:

    • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.
    • Blood pressure of >150/100 mmHg
    • Unstable angina
    • New York Heart Association (NYHA) Grade II or greater congestive heart failure
    • History of myocardial infarction within 6 months
    • History of stroke within 6 months
    • Clinically significant peripheral vascular disease
    • Evidence of bleeding diathesis or coagulopathy
    • Presence of central nervous system or brain metastases
    • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
    • Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0
    • Urine protein:creatinine ratio >= 1.0 at screening
    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
    • Serious, non-healing wound, ulcer, or bone fracture
    • Inability to comply with study and/or follow-up procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00403130

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
George Albert Fisher
Genentech
Eli Lilly and Company
Investigators
Principal Investigator: George Albert Fisher M.D. Ph.D. Stanford University
  More Information

No publications provided

Responsible Party: George Albert Fisher, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00403130     History of Changes
Other Study ID Numbers: 13761, 96052, BRSMTS0007
Study First Received: November 22, 2006
Last Updated: February 28, 2014
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on September 22, 2014