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Sorafenib and Anastrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2008 by National Cancer Institute (NCI).   Recruitment status was  Active, not recruiting

First Received on September 20, 2005.   Last Updated on May 7, 2010   History of Changes
Sponsor: Lombardi Cancer Research Center
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00217399
  Purpose

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Estradiol can cause the growth of breast cancer. Hormone therapy using anastrozole may fight breast cancer by blocking the use of estradiol by the tumor cells. Sometimes when hormone therapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to hormone therapy. Giving sorafenib together with anastrozole may reduce drug resistance and allow the tumor cells to be killed.

PURPOSE: This phase I/II trial is studying the side effects and best dose of sorafenib when given in combination with anastrozole and to see how well they work in treating postmenopausal women with metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: anastrozole
Drug: sorafenib tosylate
Phase I
Phase II

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Clinical benefit rate [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity as assessed by NCI CTCAE version 3.0 [ Designated as safety issue: Yes ]
  • Tumor marker analysis [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: June 2005
Estimated Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the clinical benefit rate of sorafenib in combination with anastrazole in women with estrogen receptor- and/or progesterone receptor-positive metastatic breast cancer.
  • Determine the recommended phase II dose of sorafenib when administered with anastrozole in these patients.

Secondary

  • Determine the toxic effects of this regimen in these patients.
  • 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.

PROJECTED ACCRUAL: A total of 15-50 patients will be accrued for this study within 2-3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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
  • Hormone receptor status:

    • 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

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Sex

  • Female

Menopausal status

  • 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

Performance status

  • ECOG 0-2

Life expectancy

  • More than 3 months

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • No bleeding diathesis

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN

Renal

  • Creatinine ≤ 1.5 times ULN

Cardiovascular

  • 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

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • More than 4 weeks since prior chemotherapy
  • No more than 2 prior chemotherapy regimens for metastatic disease

Endocrine therapy

  • See Disease Characteristics
  • At least 8 weeks since prior anastrozole therapy
  • Concurrent steroids allowed if dose is stable

Radiotherapy

  • More than 4 weeks since prior radiotherapy

Surgery

  • More than 4 weeks since prior major surgery

Other

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00217399

Locations
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520-8028
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Maryland
Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
Baltimore, Maryland, United States, 21237
United States, Virginia
Medical Oncology and Hematology Associates of North Virginia - Fairfax
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Lombardi Cancer Research Center
Investigators
Study Chair: Claudine Isaacs, MD Lombardi Cancer Research Center
  More Information

Additional Information:
No publications provided

Responsible Party: Claudine Isaacs, Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
ClinicalTrials.gov Identifier: NCT00217399     History of Changes
Other Study ID Numbers: CDR0000440067, GUMC-2004-251, NCI-6584
Study First Received: September 20, 2005
Last Updated: May 7, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
recurrent breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Anastrozole
Sorafenib
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012