Clinical trial NCT00632541: A Phase II Study of Bevacizumab + Sorafenib in Metastatic Breast Cancer
Official title: A Phase II Study of Combined VEGF Inhibitor (Bevacizumab + Sorafenib) in Patients With Metastatic Breast Cancer: Hoosier Oncology Group BRE06-109
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Bayer
name: Amgen
First posted: 2008-03-10
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Prior clinical trials involving bevacizumab and sorafenib have demonstrated single agent activity in previously treated advanced breast cancer. This trial will test combined VEGF inhibition with sorafenib and bevacizumab in less heavily pre-treated patients with advanced breast cancer.

Detailed description: OUTLINE: This is a multi-center study.

Sorafenib 200mg po daily Bevacizumab 5mg/kg every other week

1 Cycle = 4 weeks Imaging every third cycle

Acceptable toxicity and non-PD = Protocol therapy will continue Un-acceptable toxicity or PD = Protocol therapy will be discontinued

ECOG Performance Status 0-1

Life Expectancy: at least 12 weeks

Hematopoietic:

* Platelets \> 100 K/mm3
* Absolute neutrophil count (ANC) \> 1.5 K/mm3
* Hemoglobin \> 10 g/dL

Hepatic:

* Total Bilirubin \< 1.5 x ULN
* Aspartate aminotransferase (AST, SGOT) \< 2 x ULN (up to 5 x ULN in patients with known liver involvement)

Renal:

* Creatinine \< 1.5 x ULN
* No proteinuria as demonstrated by either Urine protein:creatinine (UPC) ratio \< 1.0 or Urine dipstick for proteinuria \< 2+

Cardiovascular:

* No known myocardial infarction, unstable angina, \> grade II New York Heart Association (NYHA) classification, congestive heart failure, uncontrolled hypertension defined as SBP \>150 or DBP \>100, \> grade II peripheral vascular disease or significant vascular disease (e.g. aortic aneurysm, aortic dissection) within 12 months prior to being registered for protocol therapy.
* No uncontrolled or clinically significant arrhythmia. NOTE: Controlled atrial fibrillation is allowed.
* LVEF ≥ LLN by MUGA or ECHO as obtained within 28 days prior to being registered for protocol therapy.

Pulmonary:

* No pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 within 28 days prior to being registered for protocol therapy.

Eligibility criteria: Inclusion Criteria:

* Histologic or cytologic diagnosis of breast cancer with evidence of metastatic disease. NOTE: Patients with Her-2 positive (3+ by IHC or gene amplification by FISH) are eligible only if they have had prior trastuzumab therapy.
* Must have measurable or non-measurable lesions as defined by the Response Evaluation Criteria in Solid Tumors (RECIST).
* Two or fewer prior chemotherapy regimens in any disease setting. NOTE: All adjuvant and neoadjuvant chemotherapy will be considered one regimen. NOTE: Prior hormonal therapy for metastatic disease is allowed. NOTE: Prior radiation therapy is allowed as long as the irradiated area is not the only source of evaluable disease.
* Age \> 18 years at the time of consent.
* Written informed consent and HIPAA authorization for release of personal health information.
* Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 8 weeks after treatment discontinuation.
* Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.
* Ability to comply with study and/or follow-up procedures.

Exclusion Criteria:

* No prior therapy with bevacizumab, sorafenib or any other known VEGF inhibitors.
* No known hypersensitivity to any component of the study drugs.
* No other forms of cancer therapy including radiation, chemotherapy and hormonal therapy within 21 days prior to being registered for protocol therapy.
* No history or radiologic evidence of CNS metastases including previously treated, resected, or asymptomatic brain lesions or leptominigeal involvement. A head CT or MRI must be obtained within 28 days prior to being registered for protocol therapy.
* No other participation in another clinical drug study within 28 days prior to being registered for protocol therapy.
* No known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C
* No major surgical procedure within 28 days prior to being registered for protocol therapy or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device and breast biopsy will not be considered major surgery.
* No minor surgical procedure within 7 days prior to being registered for protocol therapy.
* No known history of cerebrovascular disease including TIA, stroke or subarachnoid hemorrhage.
* No known history of ischemic bowel.
* No known history of deep venous thrombosis or pulmonary embolism.
* No history of hypertensive crisis or hypertensive encephalopathy.
* No non-healing wound or fracture.
* No active infection requiring parenteral antibiotics.
* No other hemorrhage/bleeding event ≥ CTCAE grade 3 within 28 days prior to being registered for protocol therapy.

Primary outcomes:
measure: Progression-Free Survival
timeFrame: From the start of the treatment until the criteria for disease progression is met (or death occurs) maximum of 24 months
Secondary outcomes:
measure: Assess the Clinical Benefit Response: the Proportion of Patients With Clinical Benefit (CR+PR+SD > 6 Months Duration) Will be Assessed at the Completion of the Study.
timeFrame: 6 months
measure: Assess the Overall Response Rate.
timeFrame: 24 months
measure: Determine the Adverse Event Profile of Sorafenib Combined With Bevacizumab in This Patient Population.
timeFrame: 24 months
Other outcomes:
Locations:
city: Galesburg
country: United States
facility: Medical & Surgical Specialists, LLC
state: Illinois
city: Evansville
country: United States
facility: Oncology Hematology Associates of SW Indiana
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Oncology & Hematology, Inc
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Quality Cancer Center (MCGOP)
state: Indiana
city: Lafayette
country: United States
facility: Arnett Cancer Care
state: Indiana
city: Lafayette
country: United States
facility: Horizon Oncology Center
state: Indiana
city: Muncie
country: United States
facility: Medical Consultants, P.C.
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Cleveland
country: United States
facility: Ireland Cancer Center - University Hospitals of Cleveland
state: Ohio
Study officials:
affiliation: Hoosier Oncology Group, Inc.
name: Robin T Zon, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hoosier Oncology Group, Inc.
name: Kathy Miller, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mina LA, Yu M, Johnson C, Burkhardt C, Miller KD, Zon R. A phase II study of combined VEGF inhibitor (bevacizumab+sorafenib) in patients with metastatic breast cancer: Hoosier Oncology Group Study BRE06-109. Invest New Drugs. 2013 Oct;31(5):1307-10. doi: 10.1007/s10637-013-9976-1. Epub 2013 Jun 28.