Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer

NCT00461773 | Terminated Phase 2 Results

• 1 other identifier: 0609001793
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the objective response rate of a combination of letrozole (Femara) and bevacizumab (Avastin) given preoperatively to postmenopausal patients with hormone sensitive breast cancer.

Conditions

Hormone-Sensitive Breast Cancer; Breast Cancer

Keywords

Neoadjuvant treatment

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Objective Tumor Response

  Clinical objective tumor response with 14 weeks of Neoadjuvant Letrozole combined with Bevacizumab was assessed using the following categories: Complete Response (CR): tumor is no longer visible. Partial response (PR): ≥ 50% decrease from baseline in the product of two perpendicular diameters, no new lesions. Progressive disease (PD): ≥ 25% increase of the product of two perpendicular diameters or new lesions. Stable Disease (SD): Neither CR, PR, or PD criteria met. Clinical tumor assessment was performed at baseline and every 2 weeks until week 18 prior to definitive surgery.

  Up to 18 weeks

Secondary Outcomes (5)

• Breast Conservation

  Up to 14 weeks

• Radiographic Tumor Response

  18 weeks

• Pathologic Complete Response

  Up to 18 weeks

• Tumor Response With Biological Correlates

  2 weeks

• Drug Tolerability

  Up to 18 weeks

Study Arms (2)

bevacizumab

ACTIVE COMPARATOR

brief exposure bevacizumab

Drug: Bevacizumab

bevacizumab and letrozole

ACTIVE COMPARATOR

brief exposure bevacizumab and letrozole

Drug: Letrozole; Drug: Bevacizumab

Interventions

Letrozole DRUG

Letrozole 2.5 mg po qd

Also known as: Femara

bevacizumab and letrozole

Bevacizumab DRUG

bevacizumab 10 mg/kg IV

Also known as: Avastin

bevacizumab; bevacizumab and letrozole

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed operable or potentially operable invasive breast adenocarcinoma that is clinically palpable and measurable
• Age ≥ 18 years
• Clinical Stage T2-4, N0-3, M0 (Stage II-III)
• Postmenopausal defined as Age ≥ 60 years and/or Age \>45 years with amenorrhea 12 months with an intact uterus and/or History of bilateral oophorectomy and/or FSH and estradiol levels in postmenopausal range
• ECOG PS 0, 1
• Unifocal disease
• ER and/or PR positive
• Adequate hematological, renal, and hepatic functions Absolute neutrophil count ≥ 1,500/µL Platelet count ≥ 100,000/µL creatinine ≤ 1.5 mg/dL Serum total bilirubin ≤ 1.5 mg/dL Alkaline phosphatase ≤ 3X the ULN for the reference lab SGOT/SGPT ≤ 3X the ULN for the reference lab
• Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial
• Use of effective means of contraception (men and women) in subjects of child-bearing potential

You may not qualify if:

• Prior history of and/or therapy for invasive breast cancer (includes chemotherapy, radiation, hormonal therapy including AIs, tamoxifen, raloxifene, fulvestrant or any other antiestrogen/SERM)
• Clinically significant cardiovascular disease, EF \<50%
• Known CNS disease
• History of deep vein thrombosis or pulmonary embolism
• Proteinuria at screening as demonstrated by either Urine protein:creatinine (UPC) ratio ≥ 1.0 at screening OR Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
• Presence of non-healing wound or fracture
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
• Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications)
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
• History of myocardial infarction or unstable angina within 12 months prior to study enrollment
• Any history of stroke or transient ischemic attack at any time
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
• Symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy

Sponsors & Collaborators

• Yale University: lead
• Novartis: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Yale University, Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The data reported are summaries of the available data that were collected up until the time of study termination.

Results Point of Contact

• Title: Gina G. Chung, MD
• Organization: The Christ Hospital

gina.chung@thechristhospital.com

(513) 564-7771

Study Officials

• Gina Chung, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2007
• First Posted: April 18, 2007
• Study Start: March 1, 2007
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: March 16, 2021
• Results First Posted: March 16, 2021

Record last verified: 2021-02

Locations

US (1)