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Breast CancerPhase 2NCT01439711

Letrozole in Treating Postmenopausal Women With Ductal Carcinoma in Situ

A Phase 2 study testing letrozole, MRI and conventional surgery in people with Breast Cancer, run by Alliance for Clinical Trials in Oncology at 32 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
letrozole, MRI and conventional surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
108 participants
Where
32 sitesUnited States
Study dates
Feb 2012to Jan 2018
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

Eligibility Criteria:

  1. Histologic documentation: Pathologic confirmation of ductal carcinoma in situ (DCIS) of the female breast without invasive cancer, with diagnosis rendered on core biopsy only, completed within 60 days before registration. Patients diagnosed with DCIS on the basis of surgical biopsy are not eligible for this study.
  2. Patients with microinvasion on diagnostic core biopsy, defined as tumor ≤ 1 mm in greatest dimension, will be allowed to participate.
  3. All patients must have a clip placed, either at the time of the diagnostic biopsy or at the time of the baseline MRI prior to the start of treatment.
  4. Tissue samples: Patient has diagnostic tissue available for correlative studies.
  5. Clinical stage: Tis or T1mi N0, M0
  6. Hormone receptor status: DCIS must express estrogen and/or progesterone receptor, as determined by immunohistochemical methods on the diagnostic pathology sample, according to the local institution's standard protocol. Greater than or equal to 1% cells will be considered to be positive.
  7. Menopausal status: Patients must be postmenopausal defined as:
  8. Age ≥ 55 years and one year or more of amenorrhea
  9. Age < 55 years and one year or more amenorrhea, with an estradiol assay < 20pg/ml
  10. Surgical menopause with bilateral oophorectomy (at least 28 days must elapse from surgery to time of study registration) The use of GnRH analogs to achieve post menopausal status is not allowed.
  11. Prior treatment:
  12. No prior surgical excision in the index breast for current DCIS diagnosis of DCIS
  13. Any exogenous hormone therapy must be completed 4 weeks prior to registration
  14. Any patients with a history of tamoxifen or raloxifene use within two years of current DCIS diagnosis are not eligible
  15. No prior neoadjuvant/adjuvant therapy for current DCIS diagnosis
  16. Contraindication to MRI: No contraindications to breast MRI
  17. Measurable disease: Mammographic extent of calcifications must be accurately measurable in at least one dimension with each lesion ≥ 1 cm and ≤ 7 cm
  18. DCIS must be visible on MRI based on central review.
  19. Patients with palpable DCIS or adenopathy are not eligible to participate.
  20. Patients with multifocal or bilateral disease are eligible.
  21. History of osteoporosis: Women diagnosed with osteoporosis may participate in this trial provided they are receiving appropriate therapy or if they have declined therapy.
  22. Age: Patients ≥ 18 years of age
  23. Performance Status: ECOG performance status 0 or 1
  24. Pregnancy/nursing status: Not pregnant or nursing
  25. Required Initial Laboratory Values:
  26. ANC ≥ 1,000/μL
  27. Platelet count ≥ 100,000/μL
  28. Serum creatinine ≤ 1.7 mg/dL
  29. Bilirubin ≤ 2.0 mg/dL
  30. AST/ALT ≤ 2.5 times upper limit of normal
  31. Serum estradiol level assay < 20 pg/mL *Required for patients < 55 years of age and one year or more of amenorrhea

Trial locations and contacts

32 sites in 1 country.

32 sites in 1 country

United States32 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Grant Medical Center

    Columbus, Ohio, 43215

  • Exempla Saint Joseph Hospital

    Denver, Colorado, 80218

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Saint Elizabeth Medical Center South

    Edgewood, Kentucky, 41017

  • Saint Elizabeth Fort Thomas

    Fort Thomas, Kentucky, 41075

  • Sentara Cancer Institute at Sentara CarePlex Hospital

    Hampton, Virginia, 23666

  • Margaret R Pardee Memorial Hospital

    Hendersonville, North Carolina, 28791

  • M. D. Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • Sparrow Hospital

    Lansing, Michigan, 48912

  • Baptist Health Lexington

    Lexington, Kentucky, 40503

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Delaware Clinical and Laboratory Physicians PA

    Newark, Delaware, 19713

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Regional Hematology and Oncology PA

    Newark, Delaware, 19713

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Sentara Leigh Hospital

    Norfolk, Virginia, 23502

  • Sentara Hospitals

    Norfolk, Virginia, 23507

  • Bay Area Tumor Institute

    Oakland, California, 94609

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Southern Ohio Medical Center

    Portsmouth, Ohio, 45662

  • Northwest Hospital Center

    Randallstown, Maryland, 21133

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • UCSF Medical Center-Mount Zion

    San Francisco, California, 94115

  • Missouri Baptist Medical Center

    St Louis, Missouri, 63131

Other trials in United States

About this study

Official title: Phase II Study of Neoadjuvant Letrozole for Postmenopausal Women With Estrogen Receptor Positive Ductal Carcinoma In SITU (DCIS)

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes.

PURPOSE: This phase II trial is studying how well letrozole works in treating women with ductal carcinoma in situ.

Read the detailed description

Treatment with letrozole begins within 21 days of registration, and only after notification has been received from the UCSF Breast MRI Research Laboratory that the baseline MRI is acceptable. Protocol therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a MRI for disease evaluation at months 3 and 6. All patients will continue to take study drug until the day prior to surgery, whether at month 3 or at month 6 or may stop if they experience unacceptable toxicity. It is expected that decisions regarding any adjuvant treatment (eg, radiation and hormonal therapy) will be made individually based on the best practice guidelines, using informed and shared decision making between patient and provider. The primary and secondary objectives are provided below.

Primary objective:

  1. To estimate the mean change in MRI tumor volume from pretreatment to completion of preoperative endocrine therapy in estrogen receptor-positive (ER+) ductal carcinoma in situ (DCIS), as well as to determine whether 3-month change in volume correlates with 6-month change.

Secondary objectives:

  1. To assess radiographic-pathologic correlation between MRI findings and histopathology, including the prevalence of occult invasive cancer in patients undergoing neoadjuvant endocrine therapy for DCIS.
  2. To compare changes in MRI maximum lesion diameter and mammographic extent at baseline and following treatment. These are two additional radiographic parameters which may also biological response to therapy.
  3. To determine practice patterns of adjuvant hormonal and radiation therapy in patients who complete neoadjuvant letrozole therapy for DCIS.
  4. To determine whether Ki67 is reduced with neoadjuvant letrozole treatment for DCIS, and to compare the reduction in proliferation between radiographic responders and non-responders.
  5. To identify baseline IHC and expression biomarkers predictive of response to treatment, with response determined by extent of Ki67 reduction. Subsets showing the greatest reduction in Ki67 would be the most likely candidates for non-operative treatment in future studies.
  6. To examine whether germline polymorphisms are associated with clinical endpoints, including treatment-related toxicity or efficacy outcomes, or with expression of biomarkers in serum or tumor.
  7. To assess quality-of-life and musculoskeletal symptoms associated with neoadjuvant letrozole for ER positive DCIS.

Patients will be followed up to 6 months post-surgery.

Conditions
Breast Cancer
Keywords
ductal breast carcinoma in situ, estrogen receptor-positive breast cancer
Medical subject headings
Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01439711
Study groupRoleWhat they receive
letrozole + MRI + surgeryExperimentalPatients receive letrozole (2.5 mg) one tablet each day after confirmation that the MRI is acceptable. There is a 3 and 6 month disease evaluation by MRI of both breasts. If the DCIS has grown, the patient will have surgery to remove it and will continue to take letrozole until the day before surgery. It is expected that decisions regarding any adjuvant treatment will be made individually based on best practice guidelines, using informed and shared decision making between the patient and provider.
Receives: Drug: letrozole; Procedure: MRI; Procedure: conventional surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Total MRI Functional Tumor Volume (FTV) Change From Baseline to Month 3 (V3)

    Mean total MRI FTV change from baseline to month 3 (V3): For patients with more than one measureable lesion on the MRI, the sum over all measureable lesions on the MRI was calculated at each time point. V3 was calculated by subtracting the total MRI FTV measured (i.e. the sum over all lesions present with MRI FTV measurements) at 3 months from the total MRI FTV measured at baseline. For V3 the raw change in the volume will be calculated for each patient and a mean and 95% confidence interval will be constructed using two-sided t-tests.

    Measured: up to 3 months from start of treatment

  2. Mean Total MRI Functional Tumor Volume (FTV) Change From Baseline to Month 6 (V6)

    Mean total MRI FTV change from baseline to month 6 (V6): For patients with more than one measureable lesion on the MRI, the sum over all measureable lesions on the MRI was calculated at each time point. V6 was calculated by subtracting the total MRI FTV measured at 6 months from the total MRI FTV measured at baseline. For V6 the raw change in the volume will be calculated for each patient and a mean and 95% confidence interval will be constructed using two-sided t-tests.

    Measured: up to 6 months from start of treatment

Secondary outcomes (10)

  1. Mean Total MRI Tumor Diameter Change From Baseline to Month 3

    To ascertain the change in maximum tumor diameter from baseline to 3 months (D3) the same methods as in Primary outcome #1 will be used but on diameter instead of volume. For patients with more than one lesion longest diameter measurement, the sum of all lesion longest diameter measurements was calculated.

    Measured: 3-months

  2. Change in Maximum Diameter at 6-months Based on Mammographic Measurement (MD6)

    Change in maximum diameter at 6-months based on mammographic measurement (MD6) will be estimated using the methods in Primary Outcome #1, but using the mammographic measurements instead.

    Measured: 6-months

  3. Type of Primary Surgery (Mastectomy or Lumpectomy)

    Rate of Mastectomy will be estimated as the number of mastectomies divided by the number of surgeries. A 95% confidence interval will be constructed using exact binomial methods. Rate of Lumpectomy will be estimated as the number of lumpectomies divided by the number of surgeries. A 95% confidence interval will be constructed using exact binomial methods.

    Measured: up to 6 months

  4. Number of Re-excisions Required to Obtain Clear Margins

    Measured: 3-months and 6-months

  5. Extent of Residual DCIS Post Surgery

    Measured: Up to 6 months post-surgery

  6. Presence of Invasive Cancer at Surgery

    Measured: 3-months and 6-months

  7. Size of Margins (Smallest) at Surgery

    Measured: 3-months and 6-months

  8. Incidence of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. The percentage of patients with a maximum grade 3 or higher adverse event at least possibly related to the study treatment are reported below.

    Measured: Up to 6 months post surgery

  9. Mean Total MRI Tumor Diameter Change From Baseline to Month 6

    Mean total MRI tumor diameter change from baseline to month 6: To ascertain the change in maximum tumor diameter from baseline to 6 months (D6) the same methods as in Primary Outcome #2 will be used but on diameter instead of volume.

    Measured: 6 months

  10. Mean Total MRI Tumor Diameter Change From Baseline to Month 6

    To ascertain the change in maximum tumor diameter from baseline to 6 months (D6) the same methods as in Primary outcome #2 will be used but on diameter instead of volume. For patients with more than one lesion longest diameter measurement, the sum of all lesion longest diameter measurements was calculated.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2011 (estimated)
  2. Study startFeb 2012
  3. Primary completionAug 2016
  4. Study completionJan 2018

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
108 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01439711
Sponsor's protocol ID
CALGB-40903
Other IDs
CDR0000701992, U10CA037447, NCI-2011-03452
Status last verified
Feb 2018
First submitted
21 Sep 2011
Last updated
27 Mar 2018
Data monitoring committee
Yes

Publications

  • Marks JR, Zhang D, Hardman T, Chen YY, Hall A, Simpson L, Hieken T, Bedrosian I, Price E, Sheng J, Dai Y, Lee M, Sibley AB, Owzar K, Hwang ES. Genomic alterations are associated with response to aromatase inhibitor therapy for ER-positive postmenopausal ductal carcinoma in situ: (CALGB 40903, Alliance). Breast Cancer Res. 2025 Feb 20;27(1):26. doi: 10.1186/s13058-025-01963-5.

    PubMed 39980051

  • Hwang ES, Hyslop T, Hendrix LH, Duong S, Bedrosian I, Price E, Caudle A, Hieken T, Guenther J, Hudis CA, Winer E, Lyss AP, Dickson-Witmer D, Hoefer R, Ollila DW, Hardman T, Marks J, Chen YY, Krings G, Esserman L, Hylton N. Phase II Single-Arm Study of Preoperative Letrozole for Estrogen Receptor-Positive Postmenopausal Ductal Carcinoma In Situ: CALGB 40903 (Alliance). J Clin Oncol. 2020 Apr 20;38(12):1284-1292. doi: 10.1200/JCO.19.00510. Epub 2020 Mar 3.

    PubMed 32125937

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing letrozole, MRI and conventional surgery in people with Breast Cancer, run by Alliance for Clinical Trials in Oncology at 32 sites 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?

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: finished, as of the sponsor's last update on 27 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites 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 27 Mar 2018). 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?

Mean Total MRI Functional Tumor Volume (FTV) Change From Baseline to Month 3 (V3) (time frame: up to 3 months from start of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01439711, which also lists 2 linked publications.

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 27 Mar 2018.

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