Sorafenib and Fulvestrant in Treating Patients With Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Aromatase Inhibitor Therapy

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: NCT00722072
Recruitment Status : Terminated (Sponsor pulled funding and low accrual)
First Posted : July 25, 2008
Results First Posted : September 5, 2011
Last Update Posted : February 26, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
OHSU Knight Cancer Institute

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. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving sorafenib together with fulvestrant may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving sorafenib together with fulvestrant works in treating patients with locally advanced or metastatic breast cancer that did not respond to aromatase inhibitor therapy.

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

Detailed Description:



  • To investigate the clinical activity of sorafenib tosylate and fulvestrant, as determined by a 4-month progression-free survival rate, in patients with hormone receptor-positive locally advanced or metastatic breast cancer that progressed after prior treatment with an aromatase inhibitor.


  • To determine the objective response rate in patients treated with this regimen.
  • To determine the median time to progression in patients treated with this regimen.
  • To determine the progression-free survival of patients treated with this regimen.
  • To determine the overall survival of patients treated with this regimen.
  • To establish the safety and tolerability profile of this regimen in these patients.

OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Patients also receive fulvestrant intramuscularly on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 28-56 days.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Open-Label Study of Sorafenib Plus Fulvestrant as Salvage Therapy for Hormone Receptor Positive Metastatic Breast Cancer Failing Prior Aromatase Inhibitor Treatment
Study Start Date : July 2008
Actual Primary Completion Date : July 2010
Actual Study Completion Date : July 2012

Arm Intervention/treatment
Experimental: Fulvestrant/ Sorafenib

Fulvestrant: A loading dose will be administered intramuscularly to all subjects during cycle 1 of treatment as follows:

  • 500 mg IM on Day 1
  • 250 mg IM on Day 15 Upon completion of the loading dose, a fixed dose of Fulvestrant 250 mg IM will be administered on day 1 of the next 28 day cycle and every consecutive cycle until tumor progression or unacceptable toxicity occurs requiring discontinuation.

Sorafenib: Subjects will take Sorafenib 800 mg/day administered as 400 mg bid (twice daily)each morning and evening approximately 12 hours apart. Treatment will begin on Day 1 of the study and continue daily until tumor progression or until unacceptable toxicity occurs.

Drug: fulvestrant
Loading dose for cycle 1: 500 mg intramuscular(IM) on Day 1;250 mg IM on Day 15 Upon completion of the loading dose, a fixed dose of fulvestrant 250 mg IM will be administered on day 1 of the next 28 day cycle and every consecutive cycle until tumor progression or until unacceptable toxicity occurs requiring discontinuation of study therapy

Drug: sorafenib tosylate
Subjects will take sorafenib 800 mg/day administered as 400 mg bid (twice daily) each morning and evening approximately 12 hours apart. Treatment will begin on Day 1 of the study and continue daily until tumor progression or until an unacceptable toxicity occurs which would require delay, modification or discontinuation of study therapy

Primary Outcome Measures :
  1. Number of Participants With Progression-free Survival at 4 Months [ Time Frame: 4 months after initiating treatment with sorafenib plus fulvestrant. ]
    Progression-free survival rate is defined as the proportion of subjects who are progression free (CR, PR and SD) at 4 months after initiating treatment with sorafenib plus fulvestrant. Complete Response (CR):Disappearance of all target (both measurable and evaluable)lesions. Partial Response (PR):At least a 30% decrease in the sum of the longest diameter (LD) of both measurable and evaluable target lesions. Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease(PD).

Secondary Outcome Measures :
  1. Objective Response Rate [ Time Frame: Every 8 weeks (two cycles) while receiving study therapy. ]
  2. Time to Progression [ Time Frame: Start of treatment to time of progression. ]
  3. Progression-free Survival [ Time Frame: Start of treatment to time of progression or death, whichever comes first. ]
  4. Overall Survival [ Time Frame: 28 to 56 days after discontinuation of study therapy ]

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of incurable breast cancer

    • Locally advanced or metastatic disease
  • Measurable or evaluable disease

    • Measurable disease is defined as ≥ 1 uni-dimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral computed tomography(CT) scan

      • Bone-only metastases that can be imaged with bone scan AND magnetic resonance imaging (MRI) or bone scan AND plain x-ray is considered measurable disease
      • Tumor lesions that are situated in a previously irradiated area are considered measurable only if they are progressing at the time of study entry
    • Evaluable disease includes unresectable skin/chest wall metastases that can be photographed and whose size can be measured with a ruler

      • Bone-only metastases that can only be imaged using bone scan or malignant pleural effusion(s) only are not considered evaluable disease
  • Previously treated with a third-generation aromatase inhibitor (e.g., letrozole, anastrazole, or exemestane) AND meets one of the following criteria:

    • Progressed during palliative aromatase inhibitor therapy
    • Recurred during adjuvant aromatase inhibitor therapy
    • Recurred within 12 months of completing adjuvant aromatase inhibitor therapy
  • Human Epidermal growth factor Receptor 2(HER2/neu)-negative tumor

    • No Human Epidermal growth factor Receptor 2(HER2/neu) overexpression (i.e., tumor staining 3+ by immunohistochemistry [IHC] or gene amplified by Fluorescence In Situ Hybridization [FISH])
  • Hormone receptor status:

    • Estrogen receptor and/or progesterone receptor positive, defined as ≥ 10% of malignant cells with positive nuclear staining


  • Postmenopausal
  • Eastern Cooperative Group(ECOG) performance status 0-1
  • Life expectancy ≥ 16 weeks
  • Neutrophil count ≥ 1,500/mm^³
  • Platelet count ≥ 100,000/mm^³
  • Hemoglobin ≥ 9.0 g/dL
  • Creatinine < 2 mg/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase(AST) ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)
  • International Normalized Ratio(INR) < 1.5 OR Prothrombin time/ partial thromboplastin time (PT/PTT) normal
  • Left ventricular ejection fraction(LVEF) normal by Multiple Gated Acquisition(MUGA) or ECHO
  • No known allergy to sorafenib tosylate or fulvestrant
  • No cardiac disease, including any of the following:

    • New York Heart Association(NYHA) class III-IV congestive heart failure
    • Unstable angina (anginal symptoms at rest) or new-onset angina (within the past 3 months)
    • Myocardial infarction within the past 6 months
    • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • No uncontrolled hypertension, defined as systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mm Hg despite optimal medical management
  • No thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attacks), within the past 6 months
  • No known HIV infection or chronic hepatitis B or C infection
  • No infection that requires IV antibiotics or produces a fever > 100°F within the past 72 hours
  • No pulmonary hemorrhage/bleeding event ≥ Common terminology criteria for adverse events(CTCAE) grade 2 within the past 4 weeks
  • No other hemorrhage/bleeding event ≥ CTCAE grade 3 within the past 4 weeks
  • No evidence or history of bleeding diathesis or coagulopathy
  • No significant traumatic injury within the past 2 weeks
  • No serious, nonhealing wound, ulcer, or bone fracture
  • No condition that impairs the patient's ability to swallow whole pills
  • No malabsorption problem
  • No second malignancy within the past 5 years, except adequately treated and cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No underlying medical condition that, in the principal investigator's opinion, will make the administration of study drug hazardous or would obscure the interpretation of adverse events


  • See Disease Characteristics
  • No prior chemotherapy for metastatic or unresectable locally advanced breast cancer
  • No prior sorafenib tosylate or other Vascular endothelial growth factor(VEGF)-targeting therapies
  • More than 2 weeks since prior major surgery or open biopsy
  • No concurrent anticoagulation with warfarin or heparin
  • No concurrent Hypericum perforatum (St. John wort) or rifampin
  • No other concurrent anticancer agents, including chemotherapy or biological therapy
  • No other concurrent investigational drugs
  • Concurrent bisphosphonates allowed

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): NCT00722072

United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239-3098
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Stephen Chui, MD OHSU Knight Cancer Institute

Responsible Party: OHSU Knight Cancer Institute Identifier: NCT00722072     History of Changes
Other Study ID Numbers: IRB00004318
P30CA069533 ( U.S. NIH Grant/Contract )
CDR0000601002 ( Registry Identifier: NCI PDQ )
First Posted: July 25, 2008    Key Record Dates
Results First Posted: September 5, 2011
Last Update Posted: February 26, 2018
Last Verified: January 2018

Keywords provided by OHSU Knight Cancer Institute:
male breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Aromatase Inhibitors
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Steroid Synthesis Inhibitors