Hormone-Sensitive Breast CancerPhase 2NCT00461773
Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer
A Phase 2 study testing Letrozole and Bevacizumab in people with Hormone-Sensitive Breast Cancer and Breast Cancer, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Hormone-Sensitive Breast Cancer, Breast Cancer
- What is being tested?
- Letrozole and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to May 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale University, Yale Cancer Center
New Haven, Connecticut, 06520
About this study
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
- Being tested
- Letrozole, Bevacizumab
- Keywords
- Neoadjuvant treatment
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetrozoleDrug
Also called Femara
Letrozole 2.5 mg po qd
BevacizumabDrug
Also called Avastin
bevacizumab 10 mg/kg IV
| Study group | Role | What they receive |
|---|---|---|
| bevacizumab | Active comparator | brief exposure bevacizumab Receives: Drug: Bevacizumab |
| bevacizumab and letrozole | Active comparator | brief exposure bevacizumab and letrozole Receives: Drug: Letrozole; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 18 weeks
Secondary outcomes (5)
Breast Conservation
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:
- Breast conserving surgery performed; 2. Mastectomy performed 3. No surgery performed (reason should be specified).
Measured: Up to 14 weeks
Radiographic Tumor Response
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
Measured: 18 weeks
Pathologic Complete Response
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
Measured: Up to 18 weeks
Tumor Response With Biological Correlates
To correlate response with biological correlates detected at baseline and after 1 cycle of treatment with either Bevacizumab alone or Bevacizumab combined with Letrozole.
Measured: 2 weeks
Drug Tolerability
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.
Measured: Up to 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2007 (estimated)
- Study startMar 2007
- Primary completionMay 2010
- Study completionMay 2010
Why it stopped: Lack of recrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hormone-Sensitive Breast CancerStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Gina Chung, M.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00461773
- Sponsor's protocol ID
- 0609001793
- Status last verified
- Feb 2021
- First submitted
- 16 Apr 2007
- Last updated
- 16 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT00461773
- Acronym / sponsor ID
- 0609001793
- Conditions
- Hormone-Sensitive Breast Cancer, Breast Cancer
- Keywords
- Neoadjuvant treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Novartis, Genentech, Inc.
- Study start
- Mar 2007
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 18 Apr 2007 (estimated)
- Results
- Posted 16 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| bevacizumab | Active comparator | Drug: Bevacizumabbrief exposure bevacizumab |
| bevacizumab and letrozole | Active comparator | Drug: Letrozole, Drug: Bevacizumabbrief exposure bevacizumab and letrozole |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (21 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LetrozoleAlso: FemaraLetrozole 2.5 mg po qd | Drug | bevacizumab and letrozole |
| BevacizumabAlso: Avastinbevacizumab 10 mg/kg IV | Drug | bevacizumab, bevacizumab and letrozole |
Primary outcome
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.
5 secondary outcomes
Breast Conservation
Time frame: Up to 14 weeks
Radiographic Tumor Response
Time frame: 18 weeks
Pathologic Complete Response
Time frame: Up to 18 weeks
Tumor Response With Biological Correlates
Time frame: 2 weeks
Drug Tolerability
Time frame: Up to 18 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Hormone-Sensitive Breast Cancer
Not yet recruitingPhase 1
A Study to Evaluate the Effects of GDC-4198 in Combination With Letrozole, Fulvestrant, or Giredestrant in Participants With Locally Advanced or Metastatic Hormone Receptor-Positive, HER2-Negatve Breast Cancer
Advanced or Metastatic Breast Cancer
RecruitingPhase 1/2
Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001)
High Grade Epithelial Ovarian Cancer, High Grade Serous Ovarian Cancer
RecruitingPhase 3
A Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/6 Inhibitor and Letrozole vs Placebo + CDK4/6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer
Breast Cancer
RecruitingPhase 1/2
Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs.
Metastatic Breast Cancer, HER2-negative Breast Cancer
Not yet recruitingObservational study
Long Term Cohort Study of Adding Ovarian Function Suppression to Tamoxifen in Young Women
Breast Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gina Chung, M.D. principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Letrozole and Bevacizumab in people with Hormone-Sensitive Breast Cancer and Breast Cancer, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Objective Tumor Response (time frame: Up to 18 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2021.