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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by Yale University.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Novartis
Genentech
Information provided by:
Yale University
ClinicalTrials.gov Identifier:
NCT00461773
First received: April 16, 2007
Last updated: June 5, 2009
Last verified: June 2009
  Purpose

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.


Condition Intervention Phase
Hormone-Sensitive Breast Cancer
Breast Cancer
Drug: Letrozole
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • To assess clinical objective tumor response with 14 weeks of neoadjuvant letrozole combined with bevacizumab [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess breast conservation rates (actual surgery performed and baseline feasible surgery) of 14 weeks of neoadjuvant letrozole combined with bevacizumab [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
  • To assess radiographic tumor response (ultrasound, mammogram, MRI) after 14 weeks of neoadjuvant letrozole combined with bevacizumab [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
  • To assess pathologic complete response after 14 weeks of neoadjuvant letrozole combined with bevacizumab [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
  • To correlate response with biological correlates detected at baseline and after 1 cycle of treatment with either bevacizumab alone or bevacizumab combined with letrozole [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • To assess the tolerability of 14 weeks of neoadjuvant letrozole combined with bevacizumab [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: March 2007
Estimated Study Completion Date: May 2010
Estimated Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
brief exposure bevacizumab
Drug: Letrozole
Letrozole 2.5 mg po qd
Other Name: Femara
Active Comparator: 2
brief exposure bevacizumab and letrozole
Drug: Bevacizumab
bevacizumab 10 mg/kg IV
Other Name: Avastin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0
  • Core biopsy or other minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0
  • Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential is mandatory
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
  • Known hypersensitivity to any component of bevacizumab or letrozole
  • Inability to comply with study and/or follow-up procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00461773

Contacts
Contact: Jeannie Kluytenaar, RN 203-785-6523 jeannie.kluytenaar@yale.edu
Contact: Michele Alguard 203-737-5908 Michele.alguard@yale.edu

Locations
United States, Connecticut
Yale University, Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
Novartis
Genentech
Investigators
Principal Investigator: Gina Chung, M.D. Yale University
  More Information

No publications provided

Responsible Party: Gina Chung, M.D., Principal Investigator, Yale University School of Medicine
ClinicalTrials.gov Identifier: NCT00461773     History of Changes
Other Study ID Numbers: 0609001793
Study First Received: April 16, 2007
Last Updated: June 5, 2009
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Yale University:
Neoadjuvant treatment

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Letrozole
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014