Clinical trial NCT00722072: Sorafenib and Fulvestrant in Treating Patients With Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Aromatase Inhibitor Therapy
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: male breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
recurrent breast cancer
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-07-25
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: OBJECTIVES:

Primary

* 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.

Secondary

* 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.

Eligibility criteria: DISEASE CHARACTERISTICS:

* 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

PATIENT CHARACTERISTICS:

* 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

PRIOR CONCURRENT THERAPY:

* 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

Primary outcomes:
measure: Number of Participants With Progression-free Survival at 4 Months
timeFrame: 4 months after initiating treatment with sorafenib plus fulvestrant.
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Every 8 weeks (two cycles) while receiving study therapy.
measure: Time to Progression
timeFrame: Start of treatment to time of progression.
measure: Progression-free Survival
timeFrame: Start of treatment to time of progression or death, whichever comes first.
measure: Overall Survival
timeFrame: 28 to 56 days after discontinuation of study therapy
Other outcomes:
Locations:
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Stephen Chui, MD
role: PRINCIPAL_INVESTIGATOR
References: