Clinical trial NCT00493636: 1st or 2nd Line MBC (Metastatic Breast Cancer) With Previous Avastin (Bevacizumab) Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast Cancer
Lead sponsor: Accelerated Community Oncology Research Network
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2007-06-28
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: 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 outcomes:
measure: Overall Survival
timeFrame: From the date of randomization to date of death due to any cause, assessed up to 56 months.
measure: Time to Progression
timeFrame: 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.
measure: Overall Response Rate
timeFrame: 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.
measure: Duration of Overall Response
timeFrame: 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.
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Providence Cancer Center / Katmai Oncology Group LLC
state: Alaska
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Corona
country: United States
facility: Compassionate Cancer Care-Corona
state: California
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care-Fountain Valley
state: California
city: Greenbrae
country: United States
facility: California Cancer Care
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Riverside
country: United States
facility: Compassionate Cancer Care-Riverside
state: California
city: Sacramento
country: United States
facility: Sutter Cancer Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Comprehensive Cancer Center
state: California
city: Fort Collins
country: United States
facility: Front Range Cancer Specialists
state: Colorado
city: Stamford
country: United States
facility: Hematology Oncology PC / Bennett Cancer Center
state: Connecticut
city: Trumbull
country: United States
facility: Oncology Associates of Bridgeport
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Washington Cancer Institute
state: District of Columbia
city: Brooksville
country: United States
facility: Pasco Hernando Oncology Associates PA
state: Florida
city: New Port Richey
country: United States
facility: Pasco Hernando Oncology Associates PA
state: Florida
city: Augusta
country: United States
facility: Augusta Oncology Associates, PC
state: Georgia
city: Macon
country: United States
facility: Cascade Cancer Center
state: Georgia
city: Macon
country: United States
facility: Central Georgia Cancer Care
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University-Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Quincy
country: United States
facility: Quincy Medical Group
state: Illinois
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine
state: Maine
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Jefferson City
country: United States
facility: Columbia Comprehensive Cancer Care Clinic & Research Institute
state: Missouri
city: Denville
country: United States
facility: Oncology Hematology Specialists, PA
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: East Syracuse
country: United States
facility: Hematology Oncology Associates of New York
state: New York
city: Jamaica
country: United States
facility: Queens Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Presbyterian Hospital
state: North Carolina
city: Sandusky
country: United States
facility: North Coast Cancer Care
state: Ohio
city: Dunmore
country: United States
facility: Hematology Oncology of Northeast Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematology Associates
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology Oncology Associates
state: South Carolina
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Glendale
country: United States
facility: Oncology Alliance
state: Wisconsin
Study officials:
affiliation: Accelerated Community Oncology Research Network Inc
name: Lee S Schwartzberg, MD, FACP
role: STUDY_CHAIR
affiliation: Memorial Sloan Kettering Cancer Center
name: Clifford A Hudis, MD
role: STUDY_CHAIR
References:
citation: 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.