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A Phase II Study Of OSI-774 In Combination With Bevacizumab In Patients With Stage IV Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

A Phase II Study Of OSI-774 In Combination With Bevacizumab In Patients With Stage IV Breast Cancer


- Determine the efficacy of erlotinib and bevacizumab, in terms of objective response
rate, in women with previously treated stage IV breast cancer.

- Determine the toxicity of this regimen in these patients.

- Determine the time to disease progression and duration of response of patients treated
with this regimen.

- Determine the proportion of patients achieving stabilization of disease for at least 6
months after treatment with this regimen.

- Correlate the molecular profile of the primary breast tumor with response in patients
treated with this regimen.

- Correlate an analysis of circulating endothelial cells with serum markers of
angiogenesis and response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib once daily and bevacizumab IV over 30-90 minutes once every
3 weeks. Courses repeat in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 4-18.5

Inclusion Criteria


- Histologically or cytologically confirmed carcinoma of the breast

- Metastatic (stage IV) disease

- Stable or progressive disease on or after at least 1 but no more than 2 prior
conventional chemotherapy regimens for metastatic breast cancer

- Prior high-dose chemotherapy with autologous stem cell or bone marrow
transplantation is considered 1 prior regimen when administered for metastatic

- Prior adjuvant chemotherapy and/or hormonal therapy allowed, and do not count as
prior therapy

- Prior trastuzumab (Herceptin) required for HER2/neu-positive patients (3+ by
immunohistochemistry or positive by fluorescent in situ hybridization [FISH])

- Unidimensionally measurable disease

- At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

- No prior or concurrent brain metastases or primary brain tumor, as documented by CT
scan or MRI

- Hormone receptor status:

- Not specified



- 18 and over


- Male or female

Menopausal status

- Not specified

Performance status

- ECOG 0-2 OR

- Karnofsky 60-100%

Life expectancy

- More than 3 months


- WBC ≥ 3,000/mm^3

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 75,000/mm^3

- AST/ALT ≤ 2.5 times upper limit of normal

- No bleeding diathesis

- No coagulopathy


- Bilirubin normal

- AST/ALT ≤ 2.5 times upper limit of normal

- INR < 1.5 (for patients receiving warfarin)


- Creatinine normal OR

- Creatinine clearance ≥ 60 mL/min

- No grade 1 or greater proteinuria OR

- Urinary protein ≤ 500 mg/24 hours


- Ejection fraction normal by MUGA or echocardiogram

- No history of stroke

- No clinically significant cardiovascular disease (e.g., uncontrolled hypertension,
myocardial infarction, unstable angina pectoris)

- No New York Heart Association class II-IV heart disease

- No symptomatic congestive heart failure

- No serious cardiac arrhythmia requiring medication

- No grade II or greater peripheral vascular disease within the past year

- No transient ischemic attack within the past 6 months

- No cerebrovascular accident within the past 6 months

- No unstable angina within the past 6 months

- No myocardial infarction within the past 6 months

- No clinically significant peripheral artery disease within the past 6 months

- No other arterial thrombotic event within the past 6 months


- No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)

- No congenital ophthalmologic abnormality (e.g., Fuch's dystrophy)

- No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or

- No abnormal corneal sensitivity test (Schirmer test or similar tear production test)


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception

- No significant traumatic injury within the past 28 days

- No prior allergic reaction attributed to compounds of similar chemical or biological
composition to erlotinib or bevacizumab

- No history of seizures not controlled with standard medical therapy

- No serious non-healing wound, ulcer, or bone fracture

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- No other concurrent uncontrolled illness

- No gastrointestinal tract disease requiring IV alimentation

- Able to take oral medication


Biologic therapy

- See Disease Characteristics

- More than 3 weeks since prior immunotherapy

- No prior cetuximab


- See Disease Characteristics

- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

- No lifetime cumulative doxorubicin dose > 450 mg/m^2

- No lifetime cumulative epirubicin dose > 700 mg/m^2

- No lifetime cumulative doxorubicin HCl liposome dose > 550 mg/m^2

- No lifetime cumulative mitoxantrone dose > 140 mg/m^2

Endocrine therapy

- See Disease Characteristics

- More than 2 weeks since prior hormonal therapy


- More than 3 weeks since prior radiotherapy


- More than 28 days since prior major surgery or open biopsy

- No prior surgery affecting gastrointestinal absorption


- More than 3 weeks since prior investigational therapy

- No prior kinase insert domain-containing receptor (KDR) inhibitors (e.g., VEGF Trap,
SU5416, SU6668, ZD6474, PTK 757, IMC-1CII)

- No prior epidermal growth factor receptor-targeting therapy (e.g., gefitinib or

- More than 10 days since prior full-dose oral or parenteral anticoagulants or
thrombolytic agents*

- No concurrent full-dose oral or parenteral anticoagulants or thrombolytic agents*

- No concurrent chronic daily aspirin (dose > 325 mg/day)

- No concurrent nonsteroidal anti-inflammatory medications known to inhibit platelet
function (e.g., cyclo-oxygenase-1 inhibitors)

- No other concurrent investigational or commercial anticancer agents or therapies

- No concurrent combination antiretroviral therapy for HIV-positive patients NOTE:
*Except for maintaining patency of preexisting, permanent indwelling IV catheters

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Maura N. Dickler, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Federal Government

Study ID:




Start Date:

December 2002

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • male breast cancer
  • Breast Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021