1st or 2nd Line MBC (Metastatic Breast Cancer) With Previous Avastin (Bevacizumab) Therapy

May 15, 2014 updated by: Accelerated Community Oncology Research Network

A Double-Blind, Randomized Phase 2b Study of Sorafenib Compared to Placebo When Administered in Combination With Chemotherapy for Patients With Locally Advanced or MBC That Has Progressed During or After Bevacizumab Therapy

The study is being conducted to compare progression-free survival in patients treated with sorafenib and gemcitabine/capecitabine versus patients treated with placebo and gemcitabine/capecitabine for locally advanced or metastatic breast cancer that has progressed during or following treatment with a bevacizumab-containing regimen.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

160

Phase

  • Phase 2

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

  • United States
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Providence Cancer Center / Katmai Oncology Group LLC
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Highlands Oncology Group
    • California
      • Corona, California, United States, 92879
        • Compassionate Cancer Care-Corona
      • Fountain Valley, California, United States, 92879
        • Compassionate Cancer Care-Fountain Valley
      • Greenbrae, California, United States, 94904-2007
        • California Cancer Care
      • Long Beach, California, United States, 90806
        • Long Beach Memorial Medical Center
      • Riverside, California, United States, 92501
        • Compassionate Cancer Care-Riverside
      • Sacramento, California, United States, 98516
        • Sutter Cancer Center
      • San Francisco, California, United States, 94107
        • California Pacific Medical Center
      • San Francisco, California, United States, 94115
        • University of California San Francisco Comprehensive Cancer Center
    • Colorado
      • Fort Collins, Colorado, United States, 80528
        • Front Range Cancer Specialists
    • Connecticut
      • Stamford, Connecticut, United States, 06902
        • Hematology Oncology PC / Bennett Cancer Center
      • Trumbull, Connecticut, United States, 06611
        • Oncology Associates of Bridgeport
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Medical Center
      • Washington, District of Columbia, United States, 20010
        • Washington Cancer Institute
    • Florida
      • Brooksville, Florida, United States, 34613
        • Pasco Hernando Oncology Associates PA
      • New Port Richey, Florida, United States, 34652
        • Pasco Hernando Oncology Associates PA
    • Georgia
      • Augusta, Georgia, United States, 30901
        • Augusta Oncology Associates, PC
      • Macon, Georgia, United States, 31201
        • Central Georgia Cancer Care
      • Macon, Georgia, United States, 31201
        • Cascade Cancer Center
      • Marietta, Georgia, United States, 30060
        • Northwest Georgia Oncology Center
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60611
        • Northwestern University-Robert H. Lurie Comprehensive Cancer Center
      • Harvey, Illinois, United States, 60426
        • Ingalls Memorial Hospital
      • Quincy, Illinois, United States, 62301
        • Quincy Medical Group
    • Indiana
      • South Bend, Indiana, United States, 46601
        • Northern Indiana Cancer Research Consortium
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Mary Bird Perkins Cancer Center
    • Maine
      • Scarborough, Maine, United States, 04474-9308
        • Maine Center for Cancer Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
      • Springfield, Massachusetts, United States, 01107
        • Baystate Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • University of Michigan Comprehensive Cancer Center
    • Missouri
      • Jefferson City, Missouri, United States, 65109
        • Columbia Comprehensive Cancer Care Clinic & Research Institute
    • New Jersey
      • Denville, New Jersey, United States, 07134
        • Oncology Hematology Specialists, PA
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • East Syracuse, New York, United States, 13057
        • Hematology Oncology Associates of New York
      • Jamaica, New York, United States, 11432
        • Queens Cancer Center
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Presbyterian Hospital
    • Ohio
      • Sandusky, Ohio, United States, 44870
        • North Coast Cancer Care
    • Pennsylvania
      • Dunmore, Pennsylvania, United States, 18512
        • Hematology Oncology of Northeast Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19106
        • Pennsylvania Oncology Hematology Associates
    • South Carolina
      • Charleston, South Carolina, United States, 29403
        • Charleston Hematology Oncology Associates
    • Tennessee
      • Memphis, Tennessee, United States, 38120
        • The West Clinic
    • Wisconsin
      • Glendale, Wisconsin, United States, 53212
        • Oncology Alliance

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

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the breast.
  • Measurable or evaluable locally advanced or metastatic disease.
  • Age ≥18 years.
  • Disease progression during or after treatment with a bevacizumab-containing regimen in the adjuvant or first-line metastatic setting.
  • Patients must have discontinued chemotherapy at least 3 weeks prior to randomization.
  • No more than one prior chemotherapy regimen for locally advanced or metastatic disease.
  • Prior hormonal therapy allowed provided it has been discontinued prior to randomization.
  • Prior radiation therapy is allowed but must be completed at least 3 weeks prior to randomization. Previously radiated area(s) must not be the only site of disease.
  • ECOG Performance Status of 0 or 1.
  • Adequate bone marrow, liver, and renal function
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to randomization, and must agree to use adequate contraception prior to study entry, for the duration of study participation and 28 days after the last study drug dosing.
  • Patients must be able and willing to sign a written informed consent.
  • Patients must be able to swallow and retain oral medication.

Exclusion Criteria:

  • Patients with breast cancer over-expressing human epidermal growth factor receptor 2 (HER-2) (gene amplification by FISH or 3+ over-expression by immunohistochemistry). Patients with unknown HER-2 status are not eligible.
  • Patients with active brain metastases.
  • Major surgery, open biopsy, or significant traumatic injury within 4 weeks of randomization.
  • Prior use of gemcitabine/capecitabine or sorafenib.
  • Evidence or history of bleeding diathesis or coagulopathy.
  • Serious, non-healing wound, ulcer, or bone fracture.
  • Substance abuse, or medical, psychological, or social condition that may interfere with the patient's participation in the study or evaluation of the study results.
  • Use of cytochrome P450 enzyme-inducing anti-epileptic drugs is not allowed.
  • Clinically significant cardiac disease
  • Uncontrolled hypertension
  • Thrombolic, embolic, venous, or arterial events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Pulmonary hemorrhage/bleeding event > NCI-CTCAE Grade 2 within 4 weeks of randomization.
  • Any other hemorrhage/bleeding event ≥ NCI-CTCAE Grade 3 within 4 weeks of randomization.
  • Active clinically serious infection > NCI-CTCAE Grade 2.
  • Known HIV infection or chronic hepatitis B or C (the safety and effectiveness of sorafenib in this patient population have not been studied).
  • Previous or concurrent cancer that is distinct in primary site or histology from breast cancer EXCEPT cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors [Ta and Tis] or any cancer curatively treated > 5 years prior to randomization.
  • Known or suspected allergy to sorafenib or gemcitabine/capecitabine.
  • Prior or concurrent use of St. John's Wort or rifampin (rifampicin) within 3 weeks of randomization.
  • Concurrent anti-cancer therapy other than gemcitabine/capecitabine and sorafenib/placebo.
  • Prior treatment with any agent that targets VEGF or VEGFR (licensed or investigational), except bevacizumab.
  • Women who are pregnant or breast-feeding.
  • Use of any investigational drug within 30 days or 5 half-lives, whichever is longer, preceding randomization.
  • Inability to comply with protocol and/or not willing or not available for follow-up assessments.
  • Any condition which in the investigator's opinion makes the patient unsuitable for the study participation.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: A (Sorafenib + Gemcitabine or Capecitabine)
Sorafenib will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours); Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle; Capecitabine will be administered orally at a dose of 1,000 mg/m2 twice daily, within 30 minutes after a meal, for 14 days followed by a 7 day rest period (without capecitabine)
Drug: Gemcitabine
Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle
Other Names:
  • Gemzar
Drug: Sorafenib
Sorafenib will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)
Other Names:
  • Nexavar
Drug: Capecitabine
Capecitabine will be administered orally at a dose of 1,000 mg/m2 twice daily, within 30 minutes after a meal, for 14 days followed by a 7 day rest period (without capecitabine).
Other Names:
  • Xeloda
Placebo Comparator: B (Placebo + Gemcitabine or Capecitabine)
Placebo will be administered ( 2 tablets ) orally twice daily (approximately every 12 hours); Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle; Capecitabine will be administered orally at a dose of 1,000 mg/m2 twice daily, within 30 minutes after a meal, for 14 days followed by a 7 day rest period (without capecitabine)
Drug: Gemcitabine
Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle
Other Names:
  • Gemzar
Drug: Capecitabine
Capecitabine will be administered orally at a dose of 1,000 mg/m2 twice daily, within 30 minutes after a meal, for 14 days followed by a 7 day rest period (without capecitabine).
Other Names:
  • Xeloda
Drug: Placebo
Placebo will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)
Other Names:
  • Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression Free Survival
Time Frame: From the date of randomization to date of first documented disease progression (i.e., the date on which a radiologic procedure or clinical evaluation was performed) or the date of death due to any cause, if before progression, assessed up to 39 months.
From the date of randomization to date of first documented disease progression (i.e., the date on which a radiologic procedure or clinical evaluation was performed) or the date of death due to any cause, if before progression, assessed up to 39 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: From the date of randomization to date of death due to any cause, assessed up to 56 months.
From the date of randomization to date of death due to any cause, assessed up to 56 months.
Time to Progression
Time Frame: Calculated as the time (days) from date of randomization to date of first observed disease progression (radiological or clinical, whichever is earlier), assessed up to 39 months.
Calculated as the time (days) from date of randomization to date of first observed disease progression (radiological or clinical, whichever is earlier), assessed up to 39 months.
Overall Response Rate
Time Frame: The overall tumor burden at baseline will be compared with subsequent measurements up to the date of first documented disease progression or the date of death due to any cause, if before progression, assessed up to 39 months.
Overall response rate was defined as the proportion of participants experiencing complete response (CR) and partial response (PR) as best overall response. Response was evaluated via changes from baseline in radiological tumor measurements using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.
The overall tumor burden at baseline will be compared with subsequent measurements up to the date of first documented disease progression or the date of death due to any cause, if before progression, assessed up to 39 months.
Duration of Overall Response
Time Frame: Period measured from the first documentation of complete or partial response (whichever status is recorded first) until the first date that recurrent or progressive disease or death is objectively documented.
Duration of overall response was calculated as the time (days) from first documentation of CR or PR (whichever status is recorded first) until the first date that recurrent or progressive disease (PD) or death is objectively documented. Response was evaluated via changes from baseline in radiological tumor measurements using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.
Period measured from the first documentation of complete or partial response (whichever status is recorded first) until the first date that recurrent or progressive disease or death is objectively documented.

Collaborators and Investigators

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

Sponsor

Accelerated Community Oncology Research Network

Collaborators

Amgen

Investigators

  • Study Chair: Lee S Schwartzberg, MD, FACP, Accelerated Community Oncology Research Network Inc
  • Study Chair: Clifford A Hudis, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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, 2007

Primary Completion (Actual)

September 1, 2010

Study Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

June 26, 2007

First Submitted That Met QC Criteria

June 27, 2007

First Posted (Estimate)

June 28, 2007

Study Record Updates

Last Update Posted (Estimate)

May 20, 2014

Last Update Submitted That Met QC Criteria

May 15, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACORN AC01B07

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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