Erlotinib Hydrochloride and Bevacizumab in Treating Patients With Stage IV Breast Cancer
Condition: Recurrent Breast Carcinoma; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Bevacizumab; Erlotinib Hydrochloride; Laboratory Biomarker Analysis
Intervention description: Given IV; Given PO; Correlative studies
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Erlotinib Hydrochloride; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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

          -  Absolute neutrophil count >= 1,000/ul

          -  Platelets >= 75,000/ul

          -  Total bilirubin within normal institutional limits

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT[)
             =< 2.5 X institutional upper limit of normal

          -  Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min for
             patients with creatinine levels outside institutional normal using the Cockcroft-Gault
             formula

          -  Women of childbearing potential must agree to use adequate contraception (barrier
             method of birth control) prior to study entry and for the duration of study
             participation; should a woman become pregnant or suspect she is pregnant while
             participating in this study, she should inform her treating physician immediately

          -  Patients must have breast cancer tissue available as either paraffin blocks or
             unstained slides for planned correlative science sub study

          -  Ability to understand and the willingness to sign a written informed consent document

        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

          -  Cumulative anthracycline and anthracenedione exposure as follows: doxorubicin > 450
             mg/m^2; epirubicin > 700 mg/m^2; liposomal doxorubicin > 550 mg/m^2; mitoxantrone >
             140 mg/m^2

          -  Proteinuria at baseline; subjects unexpectedly discovered to have >= 1+ proteinuria
             should undergo a 24-hour urine collection, which must be an adequate collection and
             must demonstrate =< 500 mg protein/ 24 hours to allow participation in the study

          -  Cardiac ejection fraction (multigated acquisition scan [MUGA] or echocardiogram) less
             than the local institution lower limit of normal

          -  Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjögren's
             syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp
             examination using a vital dye (e.g., fluorescein, Bengal-Rose), and/or an abnormal
             corneal sensitivity test (Schirmer test or similar tear production test)

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Clinically significant cardiovascular disease (e.g., uncontrolled hypertension,
             myocardial infarction, unstable angina), New York Heart Association (NYHA) grade II or
             greater congestive heart failure, serious cardiac arrhythmia requiring medication, or
             grade II or greater peripheral vascular disease within 1 year prior to day 0

          -  Gastrointestinal tract disease resulting in an inability to take oral medication or a
             requirement for IV alimentation, or prior surgical procedures affecting absorption

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with OSI-774

          -  Human immunodeficiency virus (HIV)-positive patients receiving combination
             anti-retroviral therapy are excluded from the study

          -  Patients with recent (within 6 months) arterial thrombotic events, including transient
             ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, myocardial
             infarction (MI), or clinically significant peripheral artery disease