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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

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

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



- 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.

Inclusion Criteria


- 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

- 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)

- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With Progression-free Survival at 4 Months

Outcome Description:

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).

Outcome Time Frame:

4 months after initiating treatment with sorafenib plus fulvestrant.

Safety Issue:


Principal Investigator

Stephen Chui, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

OHSU Knight Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

July 2008

Completion Date:

July 2012

Related Keywords:

  • Breast Cancer
  • male breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms



OHSU Knight Cancer Institute Portland, Oregon  97239