Open Label Trial for Post-Menopausal Women With Newly Diagnosed Operable Breast Cancer

A Phase II Open Label Trial of Pre-Operative (Neoadjuvant) Letrozole in Combination With Bevacizumab in Post-Menopausal Women With Newly Diagnosed Operable Breast Cancer

The purpose of this study is to determine pathological response to a maximum of 18 weeks of neoadjuvant therapy using a combination of letrozole and Bevacizumab in post-menopausal women with pathologically confirmed invasive ductal cancer or invasive lobular cancer of the breast whose tumors are hormone positive.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Letrozole in combination with Bevacizumab

Detailed Description

This is an open label, single arm, and Phase II study of the combination of Letrozole and Bevacizumab in patients with newly diagnosed breast cancer. Patients meeting the eligibility criteria and who have signed the consent form will start Letrozole 2.5 mg by mouth a day and Bevacizumab 15 mg per Kg IV every 3 weeks for 18 weeks (24 weeks if still responding at week 18 if approved by the PI). After neoadjuvant therapy, participants will undergo surgical treatment and will receive adjuvant therapy according to the treating physician.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pathologically confirmed invasive ductal carcinoma or invasive lobular carcinoma of the breast, T2-T4 / T4a-c / N0-2 / M0, with positive estrogen and/or progesterone receptors. Patients with inflammatory breast cancer will not be included (Stage IIIb). Patients previously treated patients with no measurable disease or patients with metastatic disease will be excluded.
• 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 (see Appendix B - consent form).
• Females 60 years of age (postmenopausal).
• Be ambulatory (outpatient) and have an ECOG PS <2 (Appendix F).
• Patients must have measurable disease by mammogram and/or breast ultrasound. 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 2.0 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%.
• No history of thrombosis during the previous year.

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 II or greater congestive heart failure see Appendix G)
• History of myocardial infarction within 6 months
• History of stroke within 6 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, fine needle aspirations or core biopsies within 7 days prior to Day 0
• Pregnant (positive pregnancy test) or lactating
• Urine protein: creatinine ratio 1.0 at screening. 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 cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix.
• Patients with metastatic disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary objective is to estimate the pathological complete response rate of neoadjuvant therapy in operable newly diagnosed ER+ breast cancer patients using the combination of Avastin and Letrozole.	approximately 24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
A clinical response will be based upon the Response Evaluation Criteria in Solid Tumors (RECIST Criteria).	approximately 24 weeks

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Andres Forero-Torres, MD, University of Alabama at Birmingham

Publications and helpful links

General Publications

• Vaklavas C, Roberts BS, Varley KE, Lin NU, Liu MC, Rugo HS, Puhalla S, Nanda R, Storniolo AM, Carey LA, Saleh MN, Li Y, Delossantos JF, Grizzle WE, LoBuglio AF, Myers RM, Forero-Torres A; Translational Breast Cancer Research Consortium (TBCRC). TBCRC 002: a phase II, randomized, open-label trial of preoperative letrozole with or without bevacizumab in postmenopausal women with newly diagnosed stage 2/3 hormone receptor-positive and HER2-negative breast cancer. Breast Cancer Res. 2020 Feb 18;22(1):22. doi: 10.1186/s13058-020-01258-x.

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): November 1, 2006
• Study Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 11, 2005
• First Posted (Estimate): September 12, 2005

Study Record Updates

• Last Update Posted (Estimate): January 4, 2011
• Last Update Submitted That Met QC Criteria: December 30, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: Breast cancer; Carcinoma of the breast
• 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: F041222006; UAB 0467 (Other Identifier: Institutional protocol study number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No