Sorafenib and Paclitaxel in Treating Patients With Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00622466
Recruitment Status : Unknown
Verified May 2015 by University of Texas Southwestern Medical Center.
Recruitment status was:  Active, not recruiting
First Posted : February 25, 2008
Last Update Posted : June 1, 2015
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

Brief Summary:

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with paclitaxel may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving sorafenib together with paclitaxel and to how well it works in treating patients with metastatic breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: paclitaxel Drug: sorafenib tosylate Phase 2

Detailed Description:



  • To evaluate the efficacy of sorafenib tosylate and paclitaxel by measuring tumor response, as defined by RECIST criteria, in patients with metastatic, HER2-negative breast cancer.


  • To evaluate time to disease progression in patients treated with this regimen.
  • To evaluate six-month progression-free survival of patients treated with this regimen.
  • To evaluate time to treatment failure in patients treated with this regimen.
  • To evaluate clinical benefit rate (tumor response and stable disease) at 24 weeks in patients treated with this regimen.
  • To evaluate duration of response in patients treated with this regimen.
  • To evaluate the tolerability of this regimen in these patients.
  • To examine the relationship of gene expression and tissue/serum protein markers, where available, related to response to therapy focusing on growth factor receptor pathways.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib tosylate twice daily on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 41 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Sorafenib and Paclitaxel for Measurable Metastatic HER2-Negative Breast Cancer
Study Start Date : October 2007
Estimated Primary Completion Date : December 2015
Estimated Study Completion Date : December 2015

Arm Intervention/treatment
Experimental: Sorfenib + Paclitaxel
Oral sorafenib tosylate twice daily on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15
Drug: paclitaxel
The chemotherapy drug called paclitaxel (Taxol) treats breast cancer, lung cancer, ovarian cancer and Kaposis sarcoma
Other Name: Taxol, Abraxane, Onxol

Drug: sorafenib tosylate
Sorafenib is a type of targeted therapy known as a kinase inhibitor used to treat advanced renal cell carcinoma and unresectable hepatocellular carcinoma
Other Name: Nexavar

Primary Outcome Measures :
  1. Response rate

Secondary Outcome Measures :
  1. Time to disease progression
  2. 6-month progression-free survival
  3. Time to treatment failure
  4. Clinical benefit rate (tumor and stable disease) at 24 weeks [ Time Frame: 24 weeks from patient start of treatment ]
  5. Duration of response
  6. Tolerability
  7. Relationship of gene expression and tissue/serum protein markers related to response to therapy focusing on growth factor receptor pathways

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


Inclusion criteria:

  • Histologically* confirmed breast cancer

    • Stage IV (metastatic) disease

      • Radiographic evidence of metastases NOTE: *Histological confirmation of the actual metastasis is not required.
  • Measurable disease by RECIST criteria defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (i.e., physical examination, CT scan, MRI, or x-ray) or ≥ 10 mm by spiral CT scan

    • No prior radiotherapy unless growth has been documented following radiotherapy
  • Primary tumor or metastatic tumor HER2-negative, defined as the following:

    • Immunohistochemistry of 0 or 1+ OR the equivalent, if an automated quantitative assay is used
    • HER2 fluorescent in situ hybridization (FISH) assay negative as defined by a HER2:chromosome 17 centromeric probe ratio < 1.8 (or < 2.2 if immunohistochemistry is less than 3+ or equivalent) OR equivalent values for negative FISH assays that do not normalize to chromosome 17
  • Hormone-receptor positive (estrogen receptor-[ER] or progesterone receptor [PgR]-positive) disease or hormone receptor-negative (ER- or PgR-negative) disease
  • Tumor block from initial breast cancer primary or a biopsy of a metastatic site must be available for correlative studies
  • Brain metastases allowed provided the patient is stable after completion of treatment (i.e., surgery and/or radiotherapy), asymptomatic, and off steroids with 2 consecutive stable brain scans at least 4 weeks after radiotherapy

Exclusion criteria:

  • Bone-only or other nonmeasurable-only disease
  • Newly diagnosed brain metastases


Inclusion criteria:

  • ECOG performance status 0-1
  • Life expectancy > 6 months
  • Menopausal status not specified
  • WBC ≥ 3,000/mcL
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • AST and ALT transaminases ≤ 2.5 times ULN (< 5 times ULN if liver involvement)
  • Creatinine < 1.5 times ULN OR creatinine clearance > 60 mL/min
  • INR < 1.5 OR PT/PTT normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to and during (women and men) and for at least 3 months after (men) study therapy
  • Able to swallow and absorb oral medications

Exclusion criteria:

  • Active or uncontrolled medical illness (e.g., active infection > CTCAE grade 2), including any of the following:

    • HIV or chronic hepatitis B or C
    • Uncontrolled diabetes
    • NYHA class II-IV uncompensated congestive heart failure
    • Unstable angina (anginal symptoms at rest)
    • New onset angina (i.e., began within the past 3 months)
    • Coronary artery disease
  • Myocardial infarction within the past 6 months
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • Evidence of bleeding diathesis or coagulopathy
  • Pulmonary hemorrhage/bleeding event > CTCAE grade 2 within 4 weeks of first dose of study drug
  • Any other hemorrhage/bleeding event > CTCAE grade 3 within 4 weeks of first study drug
  • Thrombotic or embolic events (i.e., cerebrovascular accident), including transient ischemic attacks within the past 6 months
  • Hypertension that cannot be controlled with medication to ≤ 150/90 mm Hg
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib tosylate
  • Prior invasive cancer other than breast cancer except nonmelanoma skin cancer
  • Chronic nonhealing wound or ulcer


  • No more than 1 prior chemotherapy regimen for metastatic breast cancer (MBC)
  • At least 3 weeks since prior hormonal therapy for MBC or adjuvant or neoadjuvant chemotherapy

    • More than 1 year since adjuvant paclitaxel
  • At least 4 weeks since major thoracic, abdominal, or pelvic surgery and recovered
  • At least 3 weeks since prior and no concurrent investigational drugs
  • Concurrent bisphosphonates allowed
  • Concurrent anticoagulation agents (i.e., warfarin or heparin) allowed
  • No anticipated need for or concurrent radiotherapy
  • No concurrent Hypericum perforatum (St. John wort) or rifampin (rifampicin)
  • No other concurrent anti-neoplastic drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00622466

United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Principal Investigator: Barbara B. Haley, MD Simmons Cancer Center

Responsible Party: University of Texas Southwestern Medical Center Identifier: NCT00622466     History of Changes
Other Study ID Numbers: SCCC-02107
CDR0000587470 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-2011-02791 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
First Posted: February 25, 2008    Key Record Dates
Last Update Posted: June 1, 2015
Last Verified: May 2015

Keywords provided by University of Texas Southwestern Medical Center:
stage IV breast cancer
male breast cancer
recurrent breast cancer
HER2-negative breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs