Paclitaxel and Bavituximab in Treating Patients With HER2-Negative Metastatic Breast Cancer

Stage IV Breast Cancer Clinical Trial

Official title:

A Phase I Trial of Weekly Paclitaxel in Combination With Bavituximab in Patients With Her-2 Negative Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01288261
• Other study ID #: 10-0884-04
• Secondary ID: NCI-2011-00026P3
• Status: Completed
• Phase: Phase 1
• First received: January 27, 2011
• Last updated: April 20, 2016
• Start date: January 2011
• Est. completion date: July 2015

Study information

• Verified date: April 2016
• Source: University of Arizona
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bavituximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving paclitaxel together with bavituximab may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects of giving paclitaxel and bavituximab together in treating patients with Human Epidermal growth factor Receptor 2 (HER2 )-negative metastatic breast cancer

Description:

PRIMARY OBJECTIVES:

I. To determine the safety, feasibility, and tolerability of combining paclitaxel with weekly bavituximab therapy.

SECONDARY OBJECTIVES:

I. To describe changes in pharmacodynamic markers and coagulation markers in response to single agent and combined therapy.

OUTLINE:

Patients receive paclitaxel intravenously (IV) on days 1, 8, and 15 and bavituximab IV on days 1, 8, 15, and 22 (days 15 and 22 only of course 1). Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: July 2015
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent has been obtained

• Life expectancy of at least 3 months

• Histologically or cytologically confirmed, Her-2 negative breast cancer with evidence of metastatic disease

• Measurable or evaluable disease by Response Evaluation Criteria In Solid Tumors (RECIST)

• Eastern Cooperative Oncology Group (ECOG) Performance Status =< 2

• Adequate hematologic function (absolute neutrophil count [ANC] >= 1,500 cells/uL; hemoglobin >= 9 g/dL; platelets >= 100,000/uL and =< 500,000/uL)

• Adequate renal function (serum creatinine =< 1.5 mg/dL or calculated creatinine clearance >= 60 ml/min)

• Adequate hepatic function (total or direct bilirubin =< Upper Limit of Normal (ULN), Alk Phos =< 4 x ULN)

• Prothrombin time international normalized ratio within institutional normal limits

• Activated partial thromboplastin time =< 1.5 x ULN

• New York Heart Association classification I or II

• Female patients must have a negative urine pregnancy test at prestudy (not applicable to patients with bilateral oophorectomy and/or hysterectomy or to those patients who are postmenopausal)

Exclusion Criteria:

• Known history of bleeding diathesis or coagulopathy (e.g., von Willebrand Disease, Hemophilia)

• Any current evidence of clinically significant active bleeding

• Any history of significant thromboembolic events (i.e., deep vein thrombosis or pulmonary thromboembolism) within the last five years or requirement for ongoing therapy with oral or parenteral anticoagulants; central venous catheter-related thrombosis > 12 months ago and low dose anticoagulants to maintain patency of lines are allowed; patients taking anticoagulants (e.g., prophylactic heparin or enoxaparin) are required to observe the washout period of 1 week prior to study drug infusion on Study Day 1

• Concurrent hormone therapy (i.e., estrogen contraceptives, hormone replacement, anti-estrogen); patients taking concurrent hormone therapy are required to observe the washout period of 2 weeks prior to study drug infusion on Study Day 1

• Grade 2 or higher peripheral neuropathy (e.g., numbness, tingling, and/or pain in distal extremities)

• More than one prior chemotherapy regimen for metastatic disease (prior adjuvant chemotherapy or any number of prior hormonal therapies are allowed)

• Chemotherapy, immunotherapy or radiotherapy within 2 weeks of Study Day 1 or not having recovered from significant treatment-related side effects due to agents administered previously; patients who have receive nitrosoureas and mitomycin C therapy are required to observe the washout period of 6 weeks prior to study drug infusion on Study Day 1

• Allergy to polysorbate 80 or drugs containing polyoxyethylated castor oil (e.g. cyclosporine)

• Symptomatic or clinically active Central Nervous System (CNS) disease

• Major surgery within 4 weeks of Study Day 1

• Female patients pregnant or nursing

• All patients of reproductive potential must agree to use appropriate non-hormonal form of contraception

• Uncontrolled intercurrent disease (e.g., diabetes, hypertension, thyroid disease)

• Any history of angina pectoris, coronary artery disease or cerebrovascular accident, or transient ischemic attack

• A history of any condition requiring anti-platelet therapy (e.g., phosphodiesterase inhibitors, adenosine diphosphate receptor antagonists) with the exception of general cardiovascular prophylaxis with aspirin

• Cardiac arrhythmia requiring medical therapy

• Serious non-healing wound (including wound healing by secondary intention, ulcer, or bone fracture)

• Requirement for chronic daily steroid use

• Known chronic infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
• Male Breast Cancer
• Recurrent Breast Cancer
• Stage IIIC Breast Cancer
• Stage IV Breast Cancer

Intervention

Drug:
• paclitaxel
Given IV

Biological:
• bavituximab
Given IV

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative study

Locations

Country	Name	City	State
United States	Arizona Cancer Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
University of Arizona	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of grade 3 or higher toxicities associated with the combination therapy as classified using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0		One year	Yes
Secondary	Overall response rate of the regimen by RECIST		One year	No
Secondary	Progression free survival (PFS)		One year	No
Secondary	Measurable changes in levels of circulating endothelial cells (CEC), circulating endothelial progenitors (CEP), apoptotic CEC, and circulating tumor cells (CTC), as well as changes in cell-specific microparticle formation in response to therapy		One year	No
Secondary	Activation of coagulation as measured by changes in D-dimer levels and platelet activation markers in response to therapy		One year	No
Secondary	Collection and storage of additional plasma for further analysis of angiogenic markers (i.e., VCAM and VEGF)		One year	No