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A Phase I/II Trial of BAY 43-9006 (Sorafenib) in Combination With Anastrozole in Patients With Metastatic Breast Cancer

Phase 1/Phase 2
18 Years
Not Enrolling
Recurrent Breast Cancer, Stage IV Breast Cancer

Thank you

Trial Information

A Phase I/II Trial of BAY 43-9006 (Sorafenib) in Combination With Anastrozole in Patients With Metastatic Breast Cancer


I. Determine the clinical benefit rate of sorafenib in combination with anastrazole in women
with estrogen receptor- and/or progesterone receptor-positive metastatic breast cancer.

II. Determine the recommended phase II dose of sorafenib when administered with anastrozole
in these patients.


I. Determine the toxic effects of this regimen in these patients. II. Determine the changes
in Raf-MAPK and VEGF-signaling pathways in tumor tissue and stroma before and after
treatment with this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of sorafenib.

PHASE I: Patients receive oral sorafenib twice daily and oral anastrozole once daily on days

Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity. A minimum of 6 patients are treated at the MTD.

PHASE II: Patients receive sorafenib at the MTD and anastrozole as in phase I.

After completion of study treatment, patients are followed every 4-8 weeks.

Inclusion Criteria:

- Histologically or cytologically confirmed breast cancer

- Metastatic disease

- Measurable disease, defined as >=1 unidimensionally measurable lesion, including >= 1
of the following:

- Lesion >= 10 mm on CT scan (5 mm sections)

- Lesion >= 20 mm on CT scan or MRI (10 mm sections)

- Bone disease that is >= 10 mm on MRI

- Lytic bone lesions that are >= 10 mm on CT scan (with 5 mm sections) OR >= 20 mm
on plain film or CT scan (with 10 mm sections)

- Lesion >= 10 mm on physical exam

- Patients must have received >= 1 prior aromatase inhibitor in either the adjuvant or
metastatic setting and must have had either disease recurrence or disease progression
on a prior aromatase inhibitor therapy

- No brain metastases diagnosed within the past 6 months OR previously untreated brain

- Estrogen receptor-positive and/or progesterone receptor-positive, defined as > 1%
staining by immunohistochemistry or > 10 fmol/mg of protein by radio-ligand
dextran-coated steroid binding assay

- Postmenopausal, as defined by 1 of the following:

- Prior bilateral oophorectomy

- No menses for >= 12 months in patients with an intact uterus

- Follicle-stimulating hormone (FSH) in postmenopausal range in patients < 60
years of age who have had a prior hysterectomy or have been amenorrheic for >= 3

- Age >= 60 years

- Pre- or perimenopausal patients receiving monthly injections of goserelin at a
dose of 3.6 mg are eligible

- ECOG 0-2

- More than 3 months

- Absolute neutrophil count >= 1,500/mm3 Platelet count >= 100,000/mm3 No bleeding

- Bilirubin =< 1.5 times upper limit of normal (ULN AST and ALT =< 2.5 times ULN

- Systolic blood pressure (BP) < 150 mm Hg and diastolic BP < 100 mm Hg on at least one
reading prior to study entry No uncontrolled hypertension

- None of the following within the past 6 months:

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Myocardial infarction

- Cardiac arrhythmia with hemodynamic compromise

- Not pregnant or nursing

- Able to swallow oral medication

- No known HIV positivity

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- No other active invasive malignancy within the past 5 years except nonmelanoma skin
cancer or treated carcinoma in situ of the cervix

- No other uncontrolled illness

- More than 4 weeks since prior chemotherapy

- No more than 2 prior chemotherapy regimens for metastatic disease

- At least 8 weeks since prior anastrozole therapy

- Concurrent steroids allowed if dose is stable

- More than 4 weeks since prior radiotherapy

- More than 4 weeks since prior major surgery

- Recovered from prior therapy

- No prior sorafenib

- No concurrent therapeutic anticoagulation

- Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) for venous or
arterial access devices allowed provided PT and PTT are =< 1.5 times ULN

- No concurrent agents that may interact with sorafenib, including any of the

- Hypericum perforatum (St. John's wort)

- Rifampin

- P450 CYP3A4 enzyme-inducing anticonvulsants (e.g., phenytoin, carbamazepine, or

- No other concurrent investigational agents

Exclusion Criteria:

- estrogen receptor status unknown

- history of myocardial infarction within 6 months

- performance status 3

- performance status 4

- premenopausal

- progesterone receptor status unknown

- HIV positive

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete Response + Partial Response + Stable Disease > 24 Weeks

Outcome Description:

Clinical Outcome measured using Response Evaluation Criteria In Solid Tumors (RECIST,)V1.0, and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), a tumor that is neither growing nor shrinking. A patient has clinical benefit from treatment if CR + PR + SD > 24 weeks.

Outcome Time Frame:

24 weeks

Safety Issue:


Principal Investigator

Claudine Isaacs

Investigator Role:

Principal Investigator

Investigator Affiliation:

Lombardi Comprehensive Cancer Center at Georgetown University


United States: Food and Drug Administration

Study ID:




Start Date:

June 2005

Completion Date:

Related Keywords:

  • Recurrent Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms



Lombardi Comprehensive Cancer Center at Georgetown University Washington, District of Columbia  20057