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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
N/A
Not Enrolling
Female
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


PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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
1-28.

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
metastases

- 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
months

- 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
diathesis

- 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
following:

- Hypericum perforatum (St. John's wort)

- Rifampin

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

- 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:

Interventional

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:

No

Principal Investigator

Claudine Isaacs

Investigator Role:

Principal Investigator

Investigator Affiliation:

Lombardi Comprehensive Cancer Center at Georgetown University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00069

NCT ID:

NCT00217399

Start Date:

June 2005

Completion Date:

Related Keywords:

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

Name

Location

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