- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00217399
Sorafenib and Anastrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
A Phase I/II Trial of BAY 43-9006 (Sorafenib) in Combination With Anastrozole in Patients With Metastatic Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20057
- Lombardi Comprehensive Cancer Center at Georgetown University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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. |
Given orally
Other Names:
Given orally
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
1 year
|
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-).
|
1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Claudine Isaacs, Lombardi Comprehensive Cancer Center at Georgetown University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protein Kinase Inhibitors
- Hormone Antagonists
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Sorafenib
- Anastrozole
Other Study ID Numbers
- NCI-2009-00069 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- CDR0000440067
- 2004-251 (Other Identifier: Lombardi Comprehensive Cancer Center at Georgetown University)
- 6584 (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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