Sorafenib and Anastrozole in Treating Postmenopausal Women With Metastatic Breast Cancer

May 12, 2014 updated by: National Cancer Institute (NCI)

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

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. 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.

Study Overview

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

Interventional

Enrollment (Actual)

35

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Given orally
Other Names:
  • Arimidex
  • ICI-D1033
  • ANAS

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

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Claudine Isaacs, Lombardi Comprehensive Cancer Center at Georgetown University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2005

Primary Completion (Actual)

July 1, 2009

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

September 20, 2005

First Submitted That Met QC Criteria

September 20, 2005

First Posted (Estimate)

September 22, 2005

Study Record Updates

Last Update Posted (Estimate)

May 28, 2014

Last Update Submitted That Met QC Criteria

May 12, 2014

Last Verified

December 1, 2012

More Information

Terms related to this study

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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