A Phase II Study of Bevacizumab + Sorafenib in Metastatic Breast Cancer

A Phase II Study of Combined VEGF Inhibitor (Bevacizumab + Sorafenib) in Patients With Metastatic Breast Cancer: Hoosier Oncology Group BRE06-109

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Sorafenib; Drug: Bevacizumab; Other: Imaging

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Galesburg, Illinois, United States, 61401
      • Medical & Surgical Specialists, LLC
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Oncology Hematology Associates of SW Indiana
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Oncology & Hematology, Inc
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Quality Cancer Center (MCGOP)
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Center
    • Lafayette, Indiana, United States, 47904
      • Arnett Cancer Care
    • Muncie, Indiana, United States, 47303
      • Medical Consultants, P.C.
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Ireland Cancer Center - University Hospitals of Cleveland

Participation Criteria

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm A; Sorafenib 200mg po daily, Bevacizumab 5mg/kg every other week, 1 Cycle = 4 weeks. Imaging every third cycle	Drug: Sorafenib; Sorafenib 200mg po daily; Drug: Bevacizumab; Bevacizumab 5mg/kg every other week 1 Cycle = 4 weeks; Other: Imaging; Imaging every third cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	The primary objective was to assess the Progression-Free Survival of sorafenib combined with bevacizumab in patients with metastatic breast cancer. Progression is defined by RECIST as a 20% increase in the sum of the longest diameters of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) or by the appearance of a new lesion.	From the start of the treatment until the criteria for disease progression is met (or death occurs) maximum of 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	6 months
Assess the Overall Response Rate.	24 months
Determine the Adverse Event Profile of Sorafenib Combined With Bevacizumab in This Patient Population.	24 months

Collaborators and Investigators

• Sponsor: Hoosier Cancer Research Network
• Collaborators: Bayer; Genentech, Inc.; Amgen
• Investigators: Principal Investigator: Robin T Zon, M.D., Hoosier Oncology Group, Inc.; Principal Investigator: Kathy Miller, M.D., Hoosier Oncology Group, Inc.

Publications and helpful links

General Publications

• 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.

Helpful Links

• Hoosier Cancer Research Network Homepage

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: February 28, 2008
• First Submitted That Met QC Criteria: March 7, 2008
• First Posted (Estimate): March 10, 2008

Study Record Updates

• Last Update Posted (Actual): February 14, 2018
• Last Update Submitted That Met QC Criteria: February 13, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sorafenib; Bevacizumab
• Other Study ID Numbers: BRE06-109