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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00722072
• Date of registration: 24/07/2008
• Primary sponsor: OHSU Knight Cancer Institute
• Public title: Sorafenib and Fulvestrant in Treating Patients With Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Aromatase Inhibitor Therapy
• Scientific 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
• Date of first enrolment: July 2008
• Target sample size: 12
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT00722072
• Study type: Interventional
• Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Stephen Chui, MD
• Affiliation: OHSU Knight Cancer Institute

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: fulvestrant

Drug: sorafenib tosylate

Primary Outcome(s)

Number of Participants With Progression-free Survival at 4 Months [Time Frame: 4 months after initiating treatment with sorafenib plus fulvestrant.]

Secondary Outcome(s)

Objective Response Rate [Time Frame: Every 8 weeks (two cycles) while receiving study therapy.]

Overall Survival [Time Frame: 28 to 56 days after discontinuation of study therapy]

Progression-free Survival [Time Frame: Start of treatment to time of progression or death, whichever comes first.]

Safety and Tolerability Profile [Time Frame: Continuous throughout study and 28 to 56 days after discontinuation of study therapy]

Time to Progression [Time Frame: Start of treatment to time of progression.]

Secondary ID(s)

BAYER-OHSU-4318

CDR0000601002

OHSU-4318

P30CA069533

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)