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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00461773
Recruitment Status : Terminated (Lack of recrual)
First Posted : April 18, 2007
Results First Posted : March 16, 2021
Last Update Posted : March 16, 2021
Sponsor:
Collaborators:
Novartis
Genentech, Inc.
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE April 16, 2007
First Posted Date  ICMJE April 18, 2007
Results First Submitted Date  ICMJE September 10, 2020
Results First Posted Date  ICMJE March 16, 2021
Last Update Posted Date March 16, 2021
Study Start Date  ICMJE March 2007
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 22, 2021)
Number of Patients With Objective Tumor Response [ Time Frame: Up to 18 weeks ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 16, 2007)
To assess clinical objective tumor response with 14 weeks of neoadjuvant letrozole combined with bevacizumab
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2021)
  • Breast Conservation [ Time Frame: Up to 14 weeks ]
    To assess breast conservation (actual surgery performed and baseline feasible surgery) of 14 weeks of neoadjuvant letrozole combined with bevacizumab. At baseline and immediately prior to surgery, the investigator will record the extent of the least invasive feasible surgery option at that time point, according to the following categories: 1. Breast conserving surgery is feasible; 2. A mastectomy is needed; 3. Tumor is inoperable, but potentially operable after neoadjuvant treatment. Following surgery, the investigator will record the extent of the actual surgery performed according to the following categories: 1. Breast conserving surgery performed; 2. Mastectomy performed 3. No surgery performed (reason should be specified).
  • Radiographic Tumor Response [ Time Frame: 18 weeks ]
    To assess radiographic tumor response after 14 weeks of Neoadjuvant Letrozole combined with Bevacizumab, mammogram were performed at baseline and at week 18 prior to definitive surgery. Tumors response was assessed using RECIST criteria RECIST: CR: Tumor is no longer visible PR: ≥ 30% decrease from baseline in the longest diameter, no new lesions PD: ≥ 20% increase in longest diameter recorded or new lesions SD: Neither CR, PR, or PD criteria met
  • Pathologic Complete Response [ Time Frame: Up to 18 weeks ]
    To assess pathologic complete response after 14 Weeks of Neoadjuvant Letrozole combined with Bevacizumab, the pathologic response was determined on the surgically excised specimen at the time of definitive surgery. The size of the residual tumor would be measured grossly if possible and confirmed microscopically. The excised residual tumor was be assessed using RECIST criteria. RECIST: CR: Tumor is no longer visible PR: ≥ 30% decrease from baseline in the longest diameter, no new lesions PD: ≥ 20% increase in longest diameter recorded or new lesions SD: Neither CR, PR, or PD criteria met
  • Tumor Response With Biological Correlates [ Time Frame: 2 weeks ]
    To correlate response with biological correlates detected at baseline and after 1 cycle of treatment with either Bevacizumab alone or Bevacizumab combined with Letrozole.
  • Drug Tolerability [ Time Frame: Up to 18 weeks ]
    To assess the tolerability of 14 weeks of Neoadjuvant Letrozole combined with Bevacizumab, individual toxicities were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 3.0. Information about all adverse events, whether volunteered by the subject, discovered by investigator questioning, or detected through physical examination, laboratory test or other means, were collected and recorded on the Adverse Event Case Report Form and followed as appropriate. An adverse event (AE) is any undesirable sign, symptom or medical condition occurring after starting study drug (or therapy) even if the event is not considered to be related to study drug (or therapy). Study drug (or therapy) includes the drug (or therapy) under evaluation, and any reference or placebo drug (or therapy) given during any phase of the trial. AE's graded 3 or 4 would be considered serious and be reported as measures of tolerability.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2007)
  • To assess breast conservation rates (actual surgery performed and baseline feasible surgery) of 14 weeks of neoadjuvant letrozole combined with bevacizumab
  • To assess radiographic tumor response (ultrasound, mammogram, MRI) after 14 weeks of neoadjuvant letrozole combined with bevacizumab
  • To assess pathologic complete response after 14 weeks of neoadjuvant letrozole combined with bevacizumab
  • To correlate response with biological correlates detected at baseline and after 1 cycle of treatment with either bevacizumab alone or bevacizumab combined with letrozole
  • To assess the tolerability of 14 weeks of neoadjuvant letrozole combined with bevacizumab
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer
Official Title  ICMJE Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hormone-Sensitive Breast Cancer
  • Breast Cancer
Intervention  ICMJE
  • Drug: Letrozole
    Letrozole 2.5 mg po qd
    Other Name: Femara
  • Drug: Bevacizumab
    bevacizumab 10 mg/kg IV
    Other Name: Avastin
Study Arms  ICMJE
  • Active Comparator: bevacizumab
    brief exposure bevacizumab
    Intervention: Drug: Bevacizumab
  • Active Comparator: bevacizumab and letrozole
    brief exposure bevacizumab and letrozole
    Interventions:
    • Drug: Letrozole
    • Drug: Bevacizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 22, 2021)
5
Original Enrollment  ICMJE
 (submitted: April 16, 2007)
40
Actual Study Completion Date  ICMJE May 2010
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00461773
Other Study ID Numbers  ICMJE 0609001793
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Yale University
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE Yale University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Novartis
  • Genentech, Inc.
Investigators  ICMJE
Principal Investigator: Gina Chung, M.D. Yale University
PRS Account Yale University
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP