Ductal Breast Carcinoma In SituNCT00555152
Lapatinib Ditosylate in Treating Patients With Ductal Breast Carcinoma In Situ
A study testing Laboratory Biomarker Analysis and Lapatinib Ditosylate in people with Ductal Breast Carcinoma In Situ and HER2/Neu Positive, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
This randomized phase I/II trial studies the side effects and best dose of lapatinib ditosylate and to see how well it works in treating patients with ductal breast carcinoma in situ. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 21 years and older, women only
- Conditions the study is for
- Ductal Breast Carcinoma In Situ, HER2/Neu Positive
- What is being tested?
- Laboratory Biomarker Analysis and Lapatinib Ditosylate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 2 sitesUnited States
- Study dates
- 19 Aug 2009to 28 Aug 2014
- Phase
- Interventional
- 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 21 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must be premenopausal or postmenopausal
- Participants must have a diagnosis of ductal carcinoma in situ made by core needle biopsy
- The DCIS cells must have high expression of human epidermal growth factor receptor 2 (erbB2) (3+ by immunohistochemical staining or amplification by fluorescence in situ hybridization [FISH]), and/or have detectable expression of epidermal growth factor receptor (EGFR) (1+ or more by immunohistochemical staining)
- All participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
- Individuals with a diagnosis of breast cancer, non-melanoma skin cancer, cervical cancer in situ, or early bladder cancer are eligible if they have not been treated with chemotherapy, biological therapy, or breast radiotherapy to the breast currently affected by DCIS within one year; in addition, individuals with a diagnosis of breast cancer may not have used tamoxifen, raloxifene, or other antiestrogen compounds within three months of study day 1
- If subjects are of reproductive potential, they must agree to use a reliable contraceptive method or be sexually abstinent; subjects must fulfill these conditions beginning at the time of starting study medications and ending one month after study termination
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- Negative serum pregnancy test (beta-human chorionic gonadotropin [HCG]) at baseline (within 30 days of day 0) for women of child bearing potential
- Serum creatinine =< 1.5 times the institution?s upper limit of normal
- Total bilirubin =< 1.5 times the institution's upper limits of normal
- Serum glutamic oxaloacetic transaminase (SGOT) =< 1.5 times the institution's upper limits of normal
- Alkaline phosphatase =< 1.5 times the institution's upper limits of normal
- Albumin =< 1.5 times the institution's upper limits of normal
- White blood cells (WBC) > 4.0 k/uL
- Platelet count > 100,000/uL
- Hematocrit of > 30%
- Cardiac ejection fraction within normal limits for the institution by multi gated acquisition scan (MUGA) scan or normal cardiac ultrasound (defined as within the upper limit of normal [ULN] for the institution)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Willingness to refrain from donating blood to others during the study
Who cannot join
- Individuals are ineligible if they have either active cancer or a prior history of malignancies other than (e.g., breast cancer, skin cancer [basal or squamous cell carcinoma], cervical cancer in situ, or early bladder cancer [preinvasive transitional cell carcinoma of the bladder]) within the past five years
- Participants are ineligible if they are currently being treated with tamoxifen, raloxifene, or with aromatase inhibitors (letrozole, anastrozole, exemestane)
- Individuals are ineligible if they have received chemotherapy, biological therapy (e.g., Herceptin), or radiotherapy for the treatment of any cancer within 1 year or if they have received tamoxifen, raloxifene, letrozole, anastrozole, or exemestane therapy within 3 months of study day 1
- Individuals currently receiving anticoagulation therapy (e.g., Coumadin) are ineligible
- Blood urea nitrogen [BUN] > 1.5 x ULN or
- Creatinine [Cr] > 1.5 x ULN
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- SGOT > 1.5 x ULN
- Serum glutamate pyruvate transaminase (SGPT) > 1.5 x ULN
- Alkaline phosphatase > 1.5 x ULN
- Bilirubin > 1.5x ULN
- Individuals who are currently participating in a study of an investigational drug
- Pregnancy, lactation or unwillingness to use a reliable contraceptive method in women of childbearing potential
- Severe underlying chronic illness or disease, such as uncontrolled diabetes
- Individuals with known congestive heart disease or previous myocardial infarction are ineligible
- Patients taking any prohibited medications
- Individuals with hypokalemia or hypomagnesemia are ineligible unless these conditions are corrected to within normal limits before starting drug
- Individuals with congenital long QT syndrome or baseline QTcF intervals > 480 msec on electrocardiogram (EKG)
- Individuals taking anti-arrhythmics, beta blockers, or other medications that may lead to QT prolongation
- Individuals who have received a cumulative dose of anthracycline therapy greater than 500 mg/m^2 are ineligible
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
M D Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Neoadjuvant Trial of Lapatinib for the Treatment of Women With DCIS Breast Cancer
This randomized phase I/II trial studies the side effects and best dose of lapatinib ditosylate and to see how well it works in treating patients with ductal breast carcinoma in situ. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine whether lapatinib (lapatinib ditosylate) therapy at the dose of 1000 mg results in a statistically significantly lower rate of proliferation in ductal carcinoma in situ (DCIS) breast cancer cells as measured by Ki67 when compared to placebo.
II. Determine the toxicity profile and frequency of adverse events in women with DCIS breast cancer taking lapatinib at 1000 mg as compared to women taking placebo.
SECONDARY OBJECTIVES:
- Determine whether lapatinib treatment affects the incidence of DCIS seen at the time of surgical excision.
II. Determine whether treatment with lapatinib will modulate breast tissue histology or the expression of specific biomarkers in normal and DCIS breast cancer cells.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive lapatinib ditosylate orally (PO) once daily (QD) for 2-6 weeks until the time of surgery.
ARM II: Patients receive placebo PO QD for 2-6 weeks until the time of surgery.
After completion of study treatment, patients are followed for 4-5 weeks.
- Conditions
- Ductal Breast Carcinoma In Situ, HER2/Neu Positive
- Being tested
- Laboratory Biomarker Analysis, Lapatinib Ditosylate, Placebo
- Medical subject headings
- Carcinoma, Intraductal, Noninfiltrating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
Lapatinib DitosylateDrug
Also called Tykerb
Given PO
PlaceboOther
Also called placebo therapy, PLCB, sham therapy
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (lapatinib ditosylate) | Experimental | Patients receive lapatinib ditosylate PO once QD for 2-6 weeks until the time of surgery. Receives: Other: Laboratory Biomarker Analysis; Drug: Lapatinib Ditosylate |
| Arm II (placebo) | Placebo comparator | Patients receive placebo PO QD for 2-6 weeks until the time of surgery. Receives: Other: Laboratory Biomarker Analysis; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proliferation (Ki67 IHC) in Ductal Breast Carcinoma In Situ (DCIS)
Reduction in percent of Ki67 positive cells at surgery compared to baseline as a function of treatment. Analysis of the primary treatment comparison will be based on a two sample t-test comparing change in log-transformed Ki67% for placebo and treated subjects. P-values of 0.05 will be considered significant. Proliferation will be assessed by immunohistochemical (IHC) staining for Ki67, and the change in percentage of Ki67 positive cells will be compared in lapatinib-treated samples versus placebo.
Measured: 2-6 weeks from baseline to surgery, up to 6 weeks
Incidence of Adverse Events Graded According to the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) Version 3.0
Toxicity profile summarized reflects incidence by number of participants affected with adverse events by Maximum Grade 1 to 3, additional adverse event according to the NCI CTCAE version 3.0 reported in Adverse Event section results.
Measured: From baseline to 4-5 weeks after surgery
Secondary outcomes (2)
Incidence of Ductal Carcinoma in Situ Remaining at Resection
Number of participants with DCIS incidence on surgical excision. Differences in histologic response (disappearance of DCIS) will be evaluated using Fisher's exact test. Correlation analysis and linear models will be used to evaluate associations among marker values at baseline and among changes in marker values and treatment. All statistical tests will be two-sided.
Measured: 2-6 weeks from baseline to surgery, up to 6 weeks
Biomarker Analysis of Proliferation Markers
Correlation analysis and linear models will be used to evaluate associations among marker values at baseline and among changes in marker values and treatment. All statistical tests will be two-sided.
Measured: 2-6 weeks from baseline to surgery, Up to 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2007 (estimated)
- Study start19 Aug 2009
- Primary completion28 Aug 2014
- Study completion28 Aug 2014
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 Ductal Breast Carcinoma In SituStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Powel Brown, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00555152
- Sponsor's protocol ID
- NCI-2009-00875
- Other IDs
- NCI-2009-00875, 2008-0086, NCT00570453, CDR0000573719, H-19895, P50CA058183, P30CA016672
- Status last verified
- Mar 2018
- First submitted
- 6 Nov 2007
- Last updated
- 20 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Trial of Lapatinib for the Treatment of Women With DCIS Breast Cancer
- ClinicalTrials.gov ID
- NCT00555152
- Acronym / sponsor ID
- NCI-2009-00875
- Conditions
- Ductal Breast Carcinoma In Situ, HER2/Neu Positive
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 19 Aug 2009 (actual)
- Primary completion
- 28 Aug 2014 (actual)
- Study completion
- 28 Aug 2014 (actual)
- First posted
- 7 Nov 2007 (estimated)
- Results
- Posted 25 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase I/II trial studies the side effects and best dose of lapatinib ditosylate and to see how well it works in treating patients with ductal breast carcinoma in situ. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- Determine whether lapatinib (lapatinib ditosylate) therapy at the dose of 1000 mg results in a statistically significantly lower rate of proliferation in ductal carcinoma in situ (DCIS) breast cancer cells as measured by Ki67 when compared to placebo.
II. Determine the toxicity profile and frequency of adverse events in women with DCIS breast cancer taking lapatinib at 1000 mg as compared to women taking placebo.
SECONDARY OBJECTIVES:
- Determine whether lapatinib treatment affects the incidence of DCIS seen at the time of surgical excision.
II. Determine whether treatment with lapatinib will modulate breast tissue histology or the expression of specific biomarkers in normal and DCIS breast cancer cells.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive lapatinib ditosylate orally (PO) once daily (QD) for 2-6 weeks until the time of surgery.
ARM II: Patients receive placebo PO QD for 2-6 weeks until the time of surgery.
After completion of study treatment, patients are followed for 4-5 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (lapatinib ditosylate) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Lapatinib DitosylatePatients receive lapatinib ditosylate PO once QD for 2-6 weeks until the time of surgery. |
| Arm II (placebo) | Placebo comparator | Other: Laboratory Biomarker Analysis, Other: PlaceboPatients receive placebo PO QD for 2-6 weeks until the time of surgery. |
Who may qualify
- Ages
- 21 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Participants must be premenopausal or postmenopausal
- Participants must have a diagnosis of ductal carcinoma in situ made by core needle biopsy
- The DCIS cells must have high expression of human epidermal growth factor receptor 2 (erbB2) (3+ by immunohistochemical staining or amplification by fluorescence in situ hybridization [FISH]), and/or have detectable expression of epidermal growth factor receptor (EGFR) (1+ or more by immunohistochemical staining)
- All participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
- Individuals with a diagnosis of breast cancer, non-melanoma skin cancer, cervical cancer in situ, or early bladder cancer are eligible if they have not been treated with chemotherapy, biological therapy, or breast radiotherapy to the breast currently affected by DCIS within one year; in addition, individuals with a diagnosis of breast cancer may not have used tamoxifen, raloxifene, or other antiestrogen compounds within three months of study day 1
Key exclusion criteria (19 listed)
- Individuals are ineligible if they have either active cancer or a prior history of malignancies other than (e.g., breast cancer, skin cancer [basal or squamous cell carcinoma], cervical cancer in situ, or early bladder cancer [preinvasive transitional cell carcinoma of the bladder]) within the past five years
- Participants are ineligible if they are currently being treated with tamoxifen, raloxifene, or with aromatase inhibitors (letrozole, anastrozole, exemestane)
- Individuals are ineligible if they have received chemotherapy, biological therapy (e.g., Herceptin), or radiotherapy for the treatment of any cancer within 1 year or if they have received tamoxifen, raloxifene, letrozole, anastrozole, or exemestane therapy within 3 months of study day 1
- Individuals currently receiving anticoagulation therapy (e.g., Coumadin) are ineligible
- Blood urea nitrogen [BUN] > 1.5 x ULN or
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (lapatinib ditosylate), Arm II (placebo) |
| Lapatinib DitosylateAlso: TykerbGiven PO | Drug | Arm I (lapatinib ditosylate) |
| PlaceboAlso: placebo therapy, PLCB, sham therapyGiven PO | Other | Arm II (placebo) |
Primary outcome
Proliferation (Ki67 IHC) in Ductal Breast Carcinoma In Situ (DCIS)
Time frame: 2-6 weeks from baseline to surgery, up to 6 weeks
Reduction in percent of Ki67 positive cells at surgery compared to baseline as a function of treatment. Analysis of the primary treatment comparison will be based on a two sample t-test comparing change in log-transformed Ki67% for placebo and treated subjects. P-values of 0.05 will be considered significant. Proliferation will be assessed by immunohistochemical (IHC) staining for Ki67, and the change in percentage of Ki67 positive cells will be compared in lapatinib-treated samples versus placebo.
Incidence of Adverse Events Graded According to the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) Version 3.0
Time frame: From baseline to 4-5 weeks after surgery
Toxicity profile summarized reflects incidence by number of participants affected with adverse events by Maximum Grade 1 to 3, additional adverse event according to the NCI CTCAE version 3.0 reported in Adverse Event section results.
2 secondary outcomes
Incidence of Ductal Carcinoma in Situ Remaining at Resection
Time frame: 2-6 weeks from baseline to surgery, up to 6 weeks
Biomarker Analysis of Proliferation Markers
Time frame: 2-6 weeks from baseline to surgery, Up to 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Powel Brown principal investigator
M.D. Anderson Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Laboratory Biomarker Analysis and Lapatinib Ditosylate in people with Ductal Breast Carcinoma In Situ and HER2/Neu Positive, run by National Cancer Institute (NCI) at 2 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?
The sponsor lists 18 inclusion and 19 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: finished, as of the sponsor's last update on 20 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Nov 2015). 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?
Proliferation (Ki67 IHC) in Ductal Breast Carcinoma In Situ (DCIS) (time frame: 2-6 weeks from baseline to surgery, up to 6 weeks). 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?
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 20 Apr 2018.