Breast CancerPhase 1/2NCT00290745
Tamoxifen or Letrozole in Treating Women With Ductal Carcinoma in Situ
A Phase 1/2 study testing letrozole, tamoxifen citrate and conventional surgery in people with Breast Cancer, run by University of California, San Francisco at 1 site in United States.
Trial summary
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen or 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?
- Any age, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- letrozole, tamoxifen citrate and conventional surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Feb 2002to 30 Jun 2011
- Phase
- Phase 1/2
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of ductal carcinoma in situ (DCIS) on core biopsy
- No evidence of contralateral breast disease or palpable masses on breast examination
- No presence or suspicion of invasive cancer, including contralateral invasive cancer, on core biopsy and MRI
- No documented ipsilateral axillary adenopathy
- Planning to undergo lumpectomy or mastectomy
- Estrogen receptor (ER)-positive tumor by immunohistochemistry
PATIENT CHARACTERISTICS:
- Female patient
- Premenopausal or postmenopausal
- Postmenopausal is defined by any of the following:
- No spontaneous menses for >= 1 year
- Bilateral oophorectomy
- Radiation castration and amenorrheic for >= 3 months
- Follicle-stimulating hormone (FSH) > 20 IU/L AND off all hormonal therapy (e.g., hormone replacement therapy or birth control pills) for >= 1 month
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No co-morbidities contraindicating the use of tamoxifen, including any of the following:
- Prior history of thrombotic events
- History of hypercoagulable state
- History of endometrial hyperplasia
- Abnormal vaginal bleeding
- No history of contrast dye-related allergies/reactions
- No history of metal-containing prostheses or implants
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: Primary Hormonal Therapy for Ductal Carcinoma in Situ: Exploration of a Novel Approach to the Clinical Management of Noninvasive Breast Cancer
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen or 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 clinical trial is studying how well tamoxifen or letrozole work in treating women with ductal carcinoma in situ.
Read the detailed description
OBJECTIVES:
- Determine the clinical response in women with estrogen receptor-positive ductal carcinoma in situ (DCIS) treated with neoadjuvant hormonal therapy comprising tamoxifen or letrozole, by evaluating the maximal change in tumor diameter on mammography and MRI following treatment.
- Identify those cellular antigens which are altered by hormonal therapy.
- Determine which cellular antigens are predictive of clinical response to hormonal therapy.
- Evaluate whether genomic changes or gene expression in DCIS are altered by hormonal therapy and find candidate genes which are correlated with response to treatment.
OUTLINE: This is a pilot study.
Patients who are premenopausal receive oral tamoxifen once daily for 3 months in the absence of unacceptable toxicity. Patients who are post menopausal receive oral letrozole once daily for 3 months in the absence of unacceptable toxicity.
After 3 months of hormonal therapy, patients undergo lumpectomy or mastectomy.
After completion of study treatment, patients are followed every 6 months for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
- Conditions
- Breast Cancer
- Being tested
- letrozole, tamoxifen citrate, conventional surgery, neoadjuvant therapy
- Keywords
- breast cancer in situ, ductal breast carcinoma in situ
- Medical subject headings
- Breast Neoplasms, Breast Carcinoma In Situ, Carcinoma, Intraductal, Noninfiltrating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
letrozoleDrug
tamoxifen citrateDrug
conventional surgeryProcedure or surgery
neoadjuvant therapyProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| tamoxifen or letrozole | Experimental | tamoxifen or letrozole work in treating women with ductal carcinoma in situ Receives: Drug: letrozole; Drug: tamoxifen citrate; Procedure: conventional surgery; Procedure: neoadjuvant therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Change in 6-month Tumor Volume Compared to Baseline Using Mammography
Change in size of Ductal Carcinoma in situ (DCIS) for participants on hormonal therapy, as determined by mammography are determined by (1) largest diameter of tumor, as visualized on mammography (2) extent of disease on mammography (3) quantification of mammographically-detected change from baseline to 6-month and used to generate the change in tumor volume of mammographic extent of disease from baseline. Since values were not normally distributed, the median change was calculated, and Wilcoxon sign rank tests were used to evaluate the significance of these changes
Measured: Baseline and 6 months
Median Change in 6-month Tumor Volume Compared to Baseline Using Magnetic Resonance Imaging (MRI)
Change in size of Ductal Carcinoma in situ (DCIS) on hormonal therapy, as determined by MRI are determined by (1) largest diameter of tumor, as visualized on MRI (2) extent of disease on MRI (3) quantification of MR-detected change from baseline to 6-month and used to generate the change in tumor volume of MRI extent of disease from baseline. Since values were not normally distributed, the median change was calculated, and Wilcoxon sign rank tests were used to evaluate the significance of these changes.
Measured: Baseline and 6 months
Secondary outcomes (7)
Number of Responders to Neoadjuvant Therapy at Month 3
MRI volume response at each time point was classified as follows: 90% image-complete response (ICR90) is defined as a >90% reduction in tumor volume, 80% image-complete response (ICR80) is defined as an 81-90% reduction in tumor volume , partial response (PR) is defined as a 20-80% reduction in tumor volume, and sustained disease or progressive disease (SD/PD) defined as a <20% reduction or increase in volume.
Measured: 3 months
Number of Responders to Neoadjuvant Therapy at Month 6
MRI volume response at each time point was classified as follows: 90% image-complete response (ICR90) is defined as a >90% reduction in tumor volume, 80% image-complete response (ICR80) is defined as an 81-90% reduction in tumor volume , partial response (PR) is defined as a 20-80% reduction in tumor volume, and sustained disease or progressive disease (SD/PD) defined as a <20% reduction or increase in volume.
Measured: 6 months
Median Reduction in Tumor Volume by Estrogen Receptor Hormone (ER H-) Quartile Group
Tumor volume changes between baseline and surgery were calculated at month 6 and compared across baseline ER Hormone (H-) Score quartile. The ER H- scores are a percentage that tells you how many cells out of 100 stain positive for hormone receptors. Each participant is assigned an ER H- score at baseline with the full score range between 0 (none have receptors) and 100 (all have receptors). The participants were grouped into quartiles (four equal groups) based on their baseline ER H- score. ER H- score and the reduction in tumor volume from baseline to month 6 was measured for each quartile group.
Measured: Baseline and 6 months
Median Reduction in Tumor Volume by PgR H-score by Quartile Group
Tumor volume changes between baseline and surgery were calculated at month 6 and compared across baseline PgR Hormone (H-) Score quartile. The PgR H-scores are a percentage that tells you how many cells out of 100 stain positive for hormone receptors. Each participant is assigned a PgR H- score at baseline with the full PgR H score ranges between 0 (none have receptors) and 100 (all have receptors). The participants were grouped into quartiles (four equal groups) based on their baseline PgR H- score and the reduction in tumor volume from baseline to month 6 was measured for each quartile group.
A wilcoxon sign rank tests were used to evaluate the significance of these changes
Measured: Baseline and 6 months
Median Reduction in Tumor Volume by Ki-67 Average Score
Tumor volume changes between baseline and surgery were calculated at month 6 by Baseline Ki-67 Average Score which is divided into 2 groups: (1) <=10% or (2) >10% to 100%. In est results, the Ki-67 findings expressed as a percentage with less than 10% considered low Ki-67 expression and > than 10% or higher considered high. A "high" score means that the breast tumor is more likely to be aggressive and spread quickly. A wilcoxon sign rank tests were used to evaluate the significance of these changes
Measured: Baseline and 6 months
Correlation Between Pathologic Tumor Size at Radiographic (MRI) Tumor Size
Correlations between pathologic tumor size and maximum diameters of baseline and 6-month MRI extent of disease were evaluated using Spearman correlation coefficient measure of association. The Spearman's rank-order correlation (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.
Measured: 6 months
Correlation Between Pathologic Tumor Size and Mammographic Tumor Size
Correlations between pathologic tumor size and maximum diameters of baseline and pre-surgical mammographic extent of disease were evaluated using Spearman correlation coefficient measure of association. The Spearman's rank-order correlation (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2006 (estimated)
- Study start19 Feb 2002
- Primary completion31 Jul 2009
- Study completion30 Jun 2011
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- E. Shelley Hwang, MD, MPH, Principal investigator, University of California, San FranciscoFrederic M. Waldman, MD, PhD, Principal investigator, University of California, San FranciscoNola M. Hylton, PhD, Principal investigator, University of California, San FranciscoRita Mukhtar, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00290745
- Sponsor's protocol ID
- 017513
- Other IDs
- UCSF-H10367-19435-05, NCI-2011-01273, CDR0000465205
- Status last verified
- Nov 2020
- First submitted
- 9 Feb 2006
- Last updated
- 4 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chen YY, DeVries S, Anderson J, Lessing J, Swain R, Chin K, Shim V, Esserman LJ, Waldman FM, Hwang ES. Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ. BMC Cancer. 2009 Aug 18;9:285. doi: 10.1186/1471-2407-9-285.
PubMed 19689789Swain RS, Chen YY, Wa C, et al.: Pathologic and biologic response to neoadjuvant anti-estrogen (AE) therapy in patients with ductal carcinoma in situ (DCIS). [Abstract] United States and Canadian Academy of Pathology 95th Annual Meeting, February 11-17, 2006, Atlanta, GA. A-186, 2006.
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Primary Hormonal Therapy for Ductal Carcinoma in Situ: Exploration of a Novel Approach to the Clinical Management of Noninvasive Breast Cancer
- ClinicalTrials.gov ID
- NCT00290745
- Acronym / sponsor ID
- 017513
- Conditions
- Breast Cancer
- Keywords
- breast cancer in situ, ductal breast carcinoma in situ
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 19 Feb 2002 (actual)
- Primary completion
- 31 Jul 2009 (actual)
- Study completion
- 30 Jun 2011 (actual)
- First posted
- 13 Feb 2006 (estimated)
- Results
- Posted 4 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen or 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 clinical trial is studying how well tamoxifen or letrozole work in treating women with ductal carcinoma in situ.
Detailed description
OBJECTIVES:
- Determine the clinical response in women with estrogen receptor-positive ductal carcinoma in situ (DCIS) treated with neoadjuvant hormonal therapy comprising tamoxifen or letrozole, by evaluating the maximal change in tumor diameter on mammography and MRI following treatment.
- Identify those cellular antigens which are altered by hormonal therapy.
- Determine which cellular antigens are predictive of clinical response to hormonal therapy.
- Evaluate whether genomic changes or gene expression in DCIS are altered by hormonal therapy and find candidate genes which are correlated with response to treatment.
OUTLINE: This is a pilot study.
Patients who are premenopausal receive oral tamoxifen once daily for 3 months in the absence of unacceptable toxicity. Patients who are post menopausal receive oral letrozole once daily for 3 months in the absence of unacceptable toxicity.
After 3 months of hormonal therapy, patients undergo lumpectomy or mastectomy.
After completion of study treatment, patients are followed every 6 months for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| tamoxifen or letrozole | Experimental | Drug: letrozole, Drug: tamoxifen citrate, Procedure: conventional surgery, Procedure: neoadjuvant therapytamoxifen or letrozole work in treating women with ductal carcinoma in situ |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 |
|---|---|---|
| letrozole | Drug | tamoxifen or letrozole |
| tamoxifen citrate | Drug | tamoxifen or letrozole |
| conventional surgery | Procedure or surgery | tamoxifen or letrozole |
| neoadjuvant therapy | Procedure or surgery | tamoxifen or letrozole |
Primary outcome
Median Change in 6-month Tumor Volume Compared to Baseline Using Mammography
Time frame: Baseline and 6 months
Change in size of Ductal Carcinoma in situ (DCIS) for participants on hormonal therapy, as determined by mammography are determined by (1) largest diameter of tumor, as visualized on mammography (2) extent of disease on mammography (3) quantification of mammographically-detected change from baseline to 6-month and used to generate the change in tumor volume of mammographic extent of disease from baseline. Since values were not normally distributed, the median change was calculated, and Wilcoxon sign rank tests were used to evaluate the significance of these changes
Median Change in 6-month Tumor Volume Compared to Baseline Using Magnetic Resonance Imaging (MRI)
Time frame: Baseline and 6 months
Change in size of Ductal Carcinoma in situ (DCIS) on hormonal therapy, as determined by MRI are determined by (1) largest diameter of tumor, as visualized on MRI (2) extent of disease on MRI (3) quantification of MR-detected change from baseline to 6-month and used to generate the change in tumor volume of MRI extent of disease from baseline. Since values were not normally distributed, the median change was calculated, and Wilcoxon sign rank tests were used to evaluate the significance of these changes.
7 secondary outcomes
Number of Responders to Neoadjuvant Therapy at Month 3
Time frame: 3 months
Number of Responders to Neoadjuvant Therapy at Month 6
Time frame: 6 months
Median Reduction in Tumor Volume by Estrogen Receptor Hormone (ER H-) Quartile Group
Time frame: Baseline and 6 months
Median Reduction in Tumor Volume by PgR H-score by Quartile Group
Time frame: Baseline and 6 months
Median Reduction in Tumor Volume by Ki-67 Average Score
Time frame: Baseline and 6 months
Correlation Between Pathologic Tumor Size at Radiographic (MRI) Tumor Size
Time frame: 6 months
Correlation Between Pathologic Tumor Size and Mammographic Tumor Size
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19689789Chen YY, DeVries S, Anderson J, Lessing J, Swain R, Chin K, Shim V, Esserman LJ, Waldman FM, Hwang ES. Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ. BMC Cancer. 2009 Aug 18;9:285. doi: 10.1186/1471-2407-9-285.
- BackgroundSwain RS, Chen YY, Wa C, et al.: Pathologic and biologic response to neoadjuvant anti-estrogen (AE) therapy in patients with ductal carcinoma in situ (DCIS). [Abstract] United States and Canadian Academy of Pathology 95th Annual Meeting, February 11-17, 2006, Atlanta, GA. A-186, 2006.
- Individual participant dataSharing planned: No
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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.
E. Shelley Hwang, MD, MPH principal investigator
University of California, San Francisco
Frederic M. Waldman, MD, PhD principal investigator
University of California, San Francisco
Nola M. Hylton, PhD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing letrozole, tamoxifen citrate and conventional surgery in people with Breast Cancer, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2020. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 4 Dec 2020). 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?
Median Change in 6-month Tumor Volume Compared to Baseline Using Mammography (time frame: Baseline and 6 months). 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 NCT00290745, 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 4 Dec 2020.