Comparing Letrozole Given Alone to Letrozole Given With Avastin in Post-Menopausal Women Breast Cancer

A Phase II, Randomized, Open Label Trial of Pre-operative (Neoadjuvant)Letrozole (Femara) vs. Letrozole in Combination With Avastin in Post Menopausal Women With Newly Diagnosed Operable Breast Cancer

This purpose of this trial is to show that the combination of Avastin and hormone therapy should be more effective than hormone therapy alone for the treatment of breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Breast Neoplasm; Cancer of the Breast
• Intervention / Treatment: Drug: Letrozole; Avastin; Other: Letrozole (Femara)

Detailed Description

Preclinical and clinical data have demonstrated that up-regulation of tumor cell VEGF is an important mechanism to subvert estrogen dependence in hormone responsive breast cancer resulting in reduced therapy response or tumor resistance to hormonal therapy; thus, it is hypothesized that the combination of an anti-VEGF agent (Avastin, an anti-VEGF monoclonal antibody) and hormonal therapy should be more effective than hormonal therapy alone for the treatment of breast cancer.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294 - 0104
      • University of Alabama at Birmingham
  • California
    • San Francisco, California, United States, 94115
      • University of California, San Francisco Comprehensive Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30341
      • Georgia Cancer Specialists
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University Of Chicago Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7600
      • University of of North Carolina at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All patients must meet the following criteria to be eligible for study entry:

• Pathologically confirmed invasive ductal carcinoma or invasive lobular carcinoma of the breast, T2-T3 / T4a-c / N0-2 / M0, with positive estrogen and/or progesterone receptors, and Her-2-neu negative. Patients with inflammatory breast cancer will not be included (T4d). Patients previously treated patients with no measurable disease or patients with metastatic disease will be excluded.
• Give written informed consent prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.

• Patients must be postmenopausal, defined as one of the following:

  • Patients > 50 years of age with no spontaneous menses for at least 12 months,
  • Bilateral oophorectomy
• Be ambulatory (outpatient) and have an ECOG PS <1.
• Patients must have measurable disease by mammogram and/or breast ultrasound (in special cases a dedicated breast MRI may be clinically indicated). The target lesion must not have been previously irradiated.
• No prior chemotherapy.
• Patients must have adequate organ and marrow function as defined as follows: absolute neutrophil count > 1,500/mm3, hemoglobin > 8.0 g/dl, platelets > 75,000/mm3, total bilirubin < 2 mg/dl, serum creatinine < 2 mg/dl, Transaminases (AST, ALT) may be up to 2 x institutional upper limit of normal. In addition < 1 gr of protein in 24 hr urine collection and urine protein/creatinine ratio < 1.0.
• No life threatening parenchymal disease or rapidly progressing disease warranting cytotoxic chemotherapy.
• Hypertension must be controlled (<150/100 mmHg).
• Ejection Fraction > 50% by echocardiogram. (LVEF greater than 75% at baseline should be reviewed and/or the test repeated as it may be falsely elevated).
• No history of thrombosis during the previous 12 months.

Exclusion Criteria:

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than this sponsor-investigator Bevacizumab cancer study.
• Uncontrolled high blood pressure (>150/100 mmHg).
• Unstable angina
• New York Heart Association (NYHA) Grade III or greater congestive heart failure
• History of myocardial infarction or unstable angina within 12 months
• History of stroke or TIA within 12 months
• Clinically significant peripheral vascular disease
• History of a bleeding disorder
• Presence of central nervous system or brain metastases
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
• Minor surgical procedures (excluding fine needle aspirations or core biopsies) within 5 days prior to Day 0
• Pregnant (positive pregnancy test) or lactating
• Urine protein: creatinine ratio greater than or equal to 1.0 at screening or patients demonstrating > 1 gr of protein in 24 hr urine collection within 4 weeks prior to study entry will not participate in the trial.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
• Serious, non-healing wound, ulcer, or bone fracture
• Unwilling or unable to comply with the protocol for the duration of the study.
• Psychiatric illness/social situations that would limit compliance with study requirements.
• History of another malignancy within the last five years except non-melanoma skin cancer and carcinoma in-situ of uterine cervix.
• Patients with metastatic disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Letrozole + Avastin; 50 evaluable patients received the combination therapy of 2.5 gm daily oral Letrozole and Avastin 15 mg/kg IV every 3 weeks for 24 weeks.	Drug: Letrozole; Avastin; Letrozole 2.5 mg PO a day and Avastin 15 mg/kg IV every 3 weeks; Other Names: Femara (Letrozole)
Experimental: Letrozole alone; 25 evaluable patients received daily oral 2.5 mg letrozole as a single agent	Other: Letrozole (Femara); Letrozole 2.5 mg PO a day for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Participants With Pathologic Complete Response	Pathological complete response is defined as the absence of residual invasive tumor in the breast or axillary lymph nodes or if only residual ductal carcinoma in-situ was seen on review of the surgical specimen.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Letrozole +Avastin	Radiographic objective response to the therapy are reported. Radiographic response was assessed using RECIST criteria by ultrasound or breast MRI through the study and are reported as complete radiographic response below.	24 weeks

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Genentech, Inc.; Breast Cancer Research Foundation

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2007
• Primary Completion (Actual): March 1, 2022
• Study Completion (Actual): March 31, 2022

Study Registration Dates

• First Submitted: September 14, 2007
• First Submitted That Met QC Criteria: September 17, 2007
• First Posted (Estimate): September 18, 2007

Study Record Updates

• Last Update Posted (Actual): October 21, 2022
• Last Update Submitted That Met QC Criteria: September 23, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Hormonal and antibody therapy for breast cancer; Hormonal therapy for breast cancer; Antibody therapy for breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Bevacizumab
• Other Study ID Numbers: F061229006; UAB 0648 (Other Identifier: Institutional protocol study number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Study Data/Documents

1. Clinical Study Report
   Information comments: Bevacizumab and Letrozole