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A Phase II Study of Letrozole in Combination With Bevacizumab in Patients With Estrogen Receptor- and/or Progesterone Receptor-Positive Unresectable Locally Advanced and/or Metastatic (Stage IV) Breast Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Female
Breast Cancer

Thank you

Trial Information

A Phase II Study of Letrozole in Combination With Bevacizumab in Patients With Estrogen Receptor- and/or Progesterone Receptor-Positive Unresectable Locally Advanced and/or Metastatic (Stage IV) Breast Cancer


OBJECTIVES:

Primary

- Determine the safety and feasibility of bevacizumab in combination with letrozole in
postmenopausal women with estrogen receptor- and/or progesterone receptor-positive,
unresectable, locally advanced or metastatic breast cancer.

Secondary

- Determine the response rate (partial response [PR] and complete response [CR]) in
patients treated with this regimen.

- Determine the clinical benefit rate (PR, CR, and stabilization of disease for ≥ 24
weeks) in patients treated with this regimen.

- Determine the time to progression in patients treated with this regimen.

- Determine the duration of response in patients treated with this regimen.

- Determine the proportion of patients treated with this regimen who have stable disease
for ≥ 24 weeks.

- Determine the molecular profile of the patient's breast tumor and explore the
relationship between these molecular characteristics and response or resistance to
treatment.

- Obtain serial measurements (pre- and post-treatment) of circulating endothelial cells
and epithelial cells and explore the relationship between these cells and serum markers
of angiogenesis and response to treatment.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral letrozole once daily on
days 1-21. Courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed carcinoma of the breast

- Locally advanced or metastatic (stage IV) disease

- Unresectable disease

- Measurable or nonmeasurable disease

- May have had stable or progressive disease after ≤ 2 prior conventional chemotherapy
regimens for treatment of locally advanced or metastatic breast cancer

- Prior chemotherapy in the adjuvant or metastatic setting is not required

- Any number of prior neoadjuvant or adjuvant chemotherapy regimens allowed

- Prior treatment with high-dose chemotherapy and autologous stem cell or bone
marrow transplantation is considered 1 regimen when administered for metastatic
disease (including induction chemotherapy and preparative regimen)

- May have had stable or responding disease on prior nonsteroidal aromatase inhibitors
(e.g., letrozole, anastrozole, or aminogluthemide)

- Any prior aromatase inhibitor-related toxicity ≥ grade 3 must have resolved ≥ 4
weeks before the start of study treatment

- May have had disease progression on other prior hormonal therapy (e.g., selective
estrogen receptor modulators [SERMs], receptor downregulators [SERDs], or ovarian
suppression) in the adjuvant or metastatic setting

- No history or evidence of primary brain tumor or brain metastases by CT scan or MRI

- Must have estrogen receptor- and/or progesterone receptor-positive tumor

PATIENT CHARACTERISTICS:

- Rendered postmenopausal with ovarian suppression (ovarian suppression with a depot
LH-RH agonist allowed) prior to the start of study treatment OR is already
postmenopausal, as defined by 1 of the criteria:

- No spontaneous menses for ≥ 12 months if the patient is ≥ 50 years old

- Amenorrheic for ≥ 12 months if the patient is < 50 years old, with serum
estradiol and follicle-stimulating hormone (FSH) levels within the institutional
postmenopausal range

- Bilateral oophorectomy

- At least 28 days since surgical oophorectomy

- Patients who have had prior hysterectomy but intact ovaries must be ≥ 55 years
old, or have serum estradiol and FSH levels within the postmenopausal range

- Ongoing ovarian suppression with a depot LH-RH agonist

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 3 months

- Female only

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

- Platelet count ≥ 75,000/mm^3

- WBC ≥ 2,500/mm^3

- AST and ALT ≤ 2.5 times upper limit of normal

- Bilirubin normal

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- No proteinuria at baseline

- Patients who unexpectedly have ≥ +1 proteinuria must undergo a 24-hour urine
collection that demonstrates ≤ 500 mg of protein over 24 hours

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No presence of bleeding diathesis or coagulopathy

- No history of allergic reaction to compounds of similar chemical or biologic
composition to letrozole or bevacizumab

- No serious, nonhealing wound, ulcer, or bone fracture

- No unstable angina pectoris

- No serious cardiac arrhythmia requiring medication

- No uncontrolled hypertension

- No myocardial infarction

- No New York Heart Association class II-IV congestive heart failure

- No peripheral vascular disease ≥ grade II within the past year

- No other clinically significant cardiovascular disease

- No history or evidence of other CNS disease by CT scan or MRI, including seizures not
controlled with standard medical therapy or stroke

- No gastrointestinal tract disease resulting in an inability to take oral medication

- No requirement for IV alimentation

- No significant traumatic injury within the past 28 days

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

- No other uncontrolled intercurrent illness

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior steroidal aromatase inhibitors (e.g., exemestane) unless administered in the
adjuvant setting (not for metastatic disease) and ≥ 12 months have elapsed since last
treatment

- Any number of prior immunotherapies (e.g., trastuzumab [Herceptin^®] or vaccines) in
the adjuvant or metastatic setting allowed

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

- More than 3 weeks since prior radiotherapy

- More than 3 weeks since prior immunotherapy

- More than 3 weeks since prior investigational therapy

- More than 2 weeks since prior hormonal therapy except letrozole therapy or a
luteinizing hormone-releasing hormone (LH-RH) agonist for ovarian suppression

- No prior surgical procedures affecting absorption

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

- At least 24 hours since prior placement of indwelling catheters

- At least 10 days since prior and no concurrent full-dose oral or parenteral
anticoagulants or thrombolytic agents except as required to maintain patency of
preexisting, permanent indwelling IV catheters

- Patients receiving warfarin should have INR < 1.5

- No prior bevacizumab

- No other prior KDR inhibitors (e.g., vascular endothelial growth factor [VEGF] Trap,
SU5416, SU6668, ZD6474, vatalanib, AEE788, or IMC-1CII)

- No other concurrent investigational agent

- No concurrent chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal
anti-inflammatory medications known to inhibit platelet function (e.g.,
cyclooxygenase-1 inhibitors)

- Concurrent bisphosphonates (e.g., zoledronate or pamidronate) or growth factors
allowed

- No other concurrent anticancer agents or therapies

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Safety

Safety Issue:

Yes

Principal Investigator

Hope S. Rugo, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, San Francisco

Authority:

United States: Institutional Review Board

Study ID:

CDR0000465198

NCT ID:

NCT00305825

Start Date:

August 2004

Completion Date:

November 2017

Related Keywords:

  • Breast Cancer
  • recurrent breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • Breast Neoplasms

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
UCSF Comprehensive Cancer CenterSan Francisco, California  94115