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

NCT ID: NCT00493636

Last Updated: 2014-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2012-11-30

Brief Summary

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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)

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle

Sorafenib

Intervention Type: DRUG

Sorafenib will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)

Capecitabine

Intervention Type: DRUG

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).

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)

Group Type: PLACEBO_COMPARATOR

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle

Placebo

Intervention Type: DRUG

Placebo will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)

Capecitabine

Intervention Type: DRUG

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).

Interventions

Gemcitabine

Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle

Intervention Type: DRUG

Sorafenib

Sorafenib will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)

Intervention Type: DRUG

Placebo

Placebo will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Gemzar; Nexavar; Sugar pill; Xeloda

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

Accelerated Community Oncology Research Network

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lee S Schwartzberg, MD, FACP

Role: STUDY_CHAIR

Accelerated Community Oncology Research Network Inc

Clifford A Hudis, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

Providence Cancer Center / Katmai Oncology Group LLC

Anchorage, Alaska, United States

Highlands Oncology Group

Fayetteville, Arkansas, United States

Compassionate Cancer Care-Corona

Corona, California, United States

Compassionate Cancer Care-Fountain Valley

Fountain Valley, California, United States

California Cancer Care

Greenbrae, California, United States

Long Beach Memorial Medical Center

Long Beach, California, United States

Compassionate Cancer Care-Riverside

Riverside, California, United States

Sutter Cancer Center

Sacramento, California, United States

California Pacific Medical Center

San Francisco, California, United States

University of California San Francisco Comprehensive Cancer Center

San Francisco, California, United States

Front Range Cancer Specialists

Fort Collins, Colorado, United States

Hematology Oncology PC / Bennett Cancer Center

Stamford, Connecticut, United States

Oncology Associates of Bridgeport

Trumbull, Connecticut, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Washington Cancer Institute

Washington D.C., District of Columbia, United States

Pasco Hernando Oncology Associates PA

Brooksville, Florida, United States

Pasco Hernando Oncology Associates PA

New Port Richey, Florida, United States

Augusta Oncology Associates, PC

Augusta, Georgia, United States

Cascade Cancer Center

Macon, Georgia, United States

Central Georgia Cancer Care

Macon, Georgia, United States

Northwest Georgia Oncology Center

Marietta, Georgia, United States

Northwestern University-Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Quincy Medical Group

Quincy, Illinois, United States

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, United States

Maine Center for Cancer Medicine

Scarborough, Maine, United States

Boston Medical Center

Boston, Massachusetts, United States

Baystate Medical Center

Springfield, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Columbia Comprehensive Cancer Care Clinic & Research Institute

Jefferson City, Missouri, United States

Oncology Hematology Specialists, PA

Denville, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Hematology Oncology Associates of New York

East Syracuse, New York, United States

Queens Cancer Center

Jamaica, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Presbyterian Hospital

Charlotte, North Carolina, United States

North Coast Cancer Care

Sandusky, Ohio, United States

Hematology Oncology of Northeast Pennsylvania

Dunmore, Pennsylvania, United States

Pennsylvania Oncology Hematology Associates

Philadelphia, Pennsylvania, United States

Charleston Hematology Oncology Associates

Charleston, South Carolina, United States

The West Clinic

Memphis, Tennessee, United States

Oncology Alliance

Glendale, Wisconsin, United States

Countries

United States

References

Schwartzberg LS, Tauer KW, Hermann RC, Makari-Judson G, Isaacs C, Beck JT, Kaklamani V, Stepanski EJ, Rugo HS, Wang W, Bell-McGuinn K, Kirshner JJ, Eisenberg P, Emanuelson R, Keaton M, Levine E, Medgyesy DC, Qamar R, Starr A, Ro SK, Lokker NA, Hudis CA. Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumab. Clin Cancer Res. 2013 May 15;19(10):2745-54. doi: 10.1158/1078-0432.CCR-12-3177. Epub 2013 Feb 26.

Reference Type: DERIVED

PMID: 23444220 (View on PubMed)

Other Identifiers

ACORN AC01B07

Identifier Type: -

Identifier Source: org_study_id