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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00493636
• Other study ID #: ACORN AC01B07
• Status: Completed
• Phase: Phase 2
• First received: June 26, 2007
• Last updated: May 15, 2014
• Start date: June 2007
• Est. completion date: November 2012

Study information

• Verified date: May 2014
• Source: Accelerated Community Oncology Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: November 2012
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Gemcitabine
Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle
• Sorafenib
Sorafenib will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)
• Placebo
Placebo will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)
• 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).

Locations

Country	Name	City	State
United States	Providence Cancer Center / Katmai Oncology Group LLC	Anchorage	Alaska
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Augusta Oncology Associates, PC	Augusta	Georgia
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Boston Medical Center	Boston	Massachusetts
United States	Pasco Hernando Oncology Associates PA	Brooksville	Florida
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Charleston Hematology Oncology Associates	Charleston	South Carolina
United States	Presbyterian Hospital	Charlotte	North Carolina
United States	Northwestern University-Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Compassionate Cancer Care-Corona	Corona	California
United States	Oncology Hematology Specialists, PA	Denville	New Jersey
United States	Hematology Oncology of Northeast Pennsylvania	Dunmore	Pennsylvania
United States	Hematology Oncology Associates of New York	East Syracuse	New York
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Compassionate Cancer Care-Fountain Valley	Fountain Valley	California
United States	Oncology Alliance	Glendale	Wisconsin
United States	California Cancer Care	Greenbrae	California
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Queens Cancer Center	Jamaica	New York
United States	Columbia Comprehensive Cancer Care Clinic & Research Institute	Jefferson City	Missouri
United States	Long Beach Memorial Medical Center	Long Beach	California
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	The West Clinic	Memphis	Tennessee
United States	Pasco Hernando Oncology Associates PA	New Port Richey	Florida
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Pennsylvania Oncology Hematology Associates	Philadelphia	Pennsylvania
United States	Quincy Medical Group	Quincy	Illinois
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	North Coast Cancer Care	Sandusky	Ohio
United States	Maine Center for Cancer Medicine	Scarborough	Maine
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Baystate Medical Center	Springfield	Massachusetts
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	District of Columbia
United States	Washington Cancer Institute	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Accelerated Community Oncology Research Network	Onyx Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival		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.	No
Secondary	Overall Survival		From the date of randomization to date of death due to any cause, assessed up to 56 months.	No
Secondary	Time to Progression		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.	No
Secondary	Overall Response Rate	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.	No
Secondary	Duration of Overall Response	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.	No