A Phase II Study of OSI-774 in Combination With Bevacizumab in Patients With Stage IV Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Recurrent Breast Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 38
- Locations
- 2
- Primary Endpoint
- Level of EGFR Expression
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This phase II trial studies how well erlotinib hydrochloride and bevacizumab work in treating patients with stage IV breast cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Giving erlotinib hydrochloride and bevacizumab may be an effective treatment for breast cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the efficacy of bevacizumab in combination with OSI-774 (erlotinib hydrochloride) in patients with previously treated metastatic breast cancer, as measured by objective response rate. SECONDARY OBJECTIVES: I. To determine the toxicity of bevacizumab in combination with OSI-774 in patients with previously treated metastatic breast cancer. II. To evaluate the efficacy of bevacizumab in combination with OSI-774 in patients with previously treated metastatic breast cancer, as measured by time to disease progression, duration of response and the proportion of patients with stabilization of disease \>= 6 months. III. To determine the molecular profile of the patient's primary breast tumor, and to explore the relationship between these molecular characteristics and the response to treatment. IV. To explore changes in biological markers in pre- and post-treatment tumor tissue in a subset of patients with accessible sites of disease. V. To explore a pre- and post-treatment analysis of circulating endothelial cells and the relationship of this analysis to serum markers of angiogenesis as well as response to treatment. VI. To obtain serial measurements of circulating epithelial cells and explore the relationship of these cells with circulating endothelial cells, markers of angiogenesis, and epidermal growth factor receptor (EGFR) expression. OUTLINE: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21 and bevacizumab intravenously (IV) over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically or cytologically confirmed carcinoma of the breast with metastatic (stage IV) disease that is currently stable or progressing after therapy
- •Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
- •Patients must have either stable disease or disease progression on or after therapy with one or two conventional chemotherapy regimens for the treatment of metastatic (stage IV) breast cancer
- •Prior treatment with high-dose chemotherapy and autologous stem cell/bone marrow transplantation is allowed, and is considered one prior regimen when administered for metastatic disease
- •There is no restriction for the number of prior hormonal therapies or immunotherapies
- •If human epidermal growth factor receptor 2 (Her2)/neu-positive (defined as 3+ by immunohistochemistry \[IHC\] or positive by fluorescence in situ hybridization \[FISH\]), prior therapy with trastuzumab required
- •Any number of prior regimens of chemotherapy and/or hormonal therapy are allowed in the adjuvant setting, and do not count towards prior therapy when determining eligibility for this trial
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- •Life expectancy of greater than 3 months
- •Leukocytes \>= 3,000/ul
Exclusion Criteria
- •Patients who have had chemotherapy, radiotherapy immunotherapy or investigational therapy within 3 weeks prior to starting treatment (6 weeks for nitrosoureas or mitomycin C), or hormonal therapy within 2 weeks prior to starting treatment
- •Patients may not be receiving any other investigational agents
- •History or evidence upon physical examination of central nervous system (CNS) disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke); all subjects must have a baseline CT or magnetic resonance imaging (MRI) of the head
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-774 or bevacizumab
- •Prior treatment with kinase insert domain receptor (KDR) inhibitors (e.g. vascular endothelial growth factor \[VEGF\] Trap, Su5416, Su6668, ZD6474, PTK757, IMC-1CII)
- •Prior treatment with EGFR targeting therapies (e.g. ZD1839 or C225)
- •Major surgery, open biopsy or significant traumatic injury occurring within 28 days prior to treatment; this does not apply to indwelling catheters, which require an interval of at least 24 hours between placement of the catheter and treatment with bevacizumab
- •Current or recent (within 10 days prior to treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents (except as required to maintain patency of preexisting, permanent indwelling IV catheters; for subjects receiving warfarin, international normalized ratio \[INR\] should be \< 1.5)
- •Chronic daily treatment with aspirin (\> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit the platelet function (e.g. cyclooxygenase \[COX\]-1 inhibitors)
- •Presence of bleeding diathesis or coagulopathy
Arms & Interventions
Treatment (erlotinib hydrochloride, bevacizumab)
Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab
Treatment (erlotinib hydrochloride, bevacizumab)
Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Erlotinib Hydrochloride
Treatment (erlotinib hydrochloride, bevacizumab)
Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Outcomes
Primary Outcomes
Level of EGFR Expression
Time Frame: Up to 12 years
Estimated at the end of the trial Immunoreactivity will be evaluated qualitatively with regard to intensity as follows: Measured on a scale, ranging from 0-3+ 0=negative (no immunoreactivity) 1+ - 3+ = positive: * faint immunoreactivity (weak staining) * intense immunoreactivity (strong staining) Immunohistochemical studies will be performed on the tumor specimen to correlate the anti-tumor efficacy of OSI-774 and bevacizumab with pre-treatment molecular characteristics.
Response Rate, Defined as Complete Response (CR) + Partial Response (PR), Using the Response Evaluation Criteria in Solid Tumors
Time Frame: Up to 12 years
Estimated at the end of the trial. Complete Response (CR):Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD 55 Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
Secondary Outcomes
- Duration of Response(From the time measurement criteria are met for CR and PR until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 years)
- Time to Progression(From the start of treatment until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 years)
- Number of Patients Evaluated for Toxicity(up to 12 years)
- Participants With Duration of Stable Disease Greater Than or Equal to 6 Months(From the start of treatment until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 years)