Sorafenib and Anastrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
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ClinicalTrials.gov Identifier: NCT00217399 |
Recruitment Status :
Completed
First Posted : September 22, 2005
Results First Posted : February 12, 2013
Last Update Posted : May 28, 2014
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Recurrent Breast Cancer Stage IV Breast Cancer | Drug: sorafenib tosylate Drug: anastrozole | Phase 1 Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 35 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase I/II Trial of BAY 43-9006 (Sorafenib) in Combination With Anastrozole in Patients With Metastatic Breast Cancer |
Study Start Date : | June 2005 |
Actual Primary Completion Date : | July 2009 |
Actual Study Completion Date : | January 2013 |

Arm | Intervention/treatment |
---|---|
Experimental: Treatment
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 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. |
Drug: sorafenib tosylate
Given orally
Other Names:
Drug: anastrozole Given orally
Other Names:
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- Complete Response + Partial Response + Stable Disease > 24 Weeks [ Time Frame: 24 weeks ]
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.
- Number of Participants With Adverse Events [ Time Frame: 1 year ]Number of patients treated with the sorafenib / anastrozole combination who experienced Grade 1-4 adverse events according to NCI common terminology criteria for adverse events (CTCAE) version 3.0
- Tumor Marker Analysis [ Time Frame: 1 year ]Number of participants with significant change in the following circulating tumor biomarkers, measured by flow cytometry: cluster designation (CD)146, CD133. Values were normalized by CD45 values(ie CD146+/CD45- and CD133+/CD45-).

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
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
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00217399
United States, District of Columbia | |
Lombardi Comprehensive Cancer Center at Georgetown University | |
Washington, District of Columbia, United States, 20057 |
Principal Investigator: | Claudine Isaacs | Lombardi Comprehensive Cancer Center at Georgetown University |
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00217399 |
Other Study ID Numbers: |
NCI-2009-00069 NCI-2009-00069 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000440067 2004-251 2004-251 ( Other Identifier: Lombardi Comprehensive Cancer Center at Georgetown University ) 6584 ( Other Identifier: CTEP ) |
First Posted: | September 22, 2005 Key Record Dates |
Results First Posted: | February 12, 2013 |
Last Update Posted: | May 28, 2014 |
Last Verified: | December 2012 |
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Sorafenib Anastrozole Antineoplastic Agents Protein Kinase Inhibitors |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Hormonal Aromatase Inhibitors Steroid Synthesis Inhibitors Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |