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Lapatinib Ditosylate in Treating Patients With Ductal Breast Carcinoma In Situ

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ClinicalTrials.gov Identifier: NCT00555152
Recruitment Status : Completed
First Posted : November 7, 2007
Results First Posted : November 25, 2015
Last Update Posted : April 20, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Ductal Breast Carcinoma In Situ
HER2/Neu Positive
Interventions Other: Laboratory Biomarker Analysis
Drug: Lapatinib Ditosylate
Other: Placebo
Enrollment 22
Recruitment Details Activated 1/17/2008 at Baylor College of Medicine (BCM), MD Anderson Cancer Center, Dana-Farber Cancer Institute, Mayo Clinic, Georgetown University & Walter Reed Army Medical Center; closed at BCM 3/8/2010, re-activated 9/19/2011 at MD Anderson, Dana-Farber Cancer Institute, Mayo Clinic & University of Alabama, Birmingham, closed 8/28/2014.
Pre-assignment Details A total of 22 participants were enrolled and randomized to 3 of 4 treatment arms; Two of the 4 initial arms were removed in the second period with one of those having no enrollment. Three participants were enrolled while the study was open at BCM, the other 19 were enrolled after the study was transferred to MD Anderson (second study period).
Arm/Group Title Arm I Lapatinib 1500 mg Arm II Lapatinib 1000 mg Arm III Lapatinib 750 mg Arm IV Placebo
Hide Arm/Group Description Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery. Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery. Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery. Placebo orally once daily for 2-6 weeks until the time of surgery.
Period Title: Period Open at BCM: 1/17/08-3/8/10
Started 2 0 [1] 0 1
Completed 2 0 0 1
Not Completed 0 0 0 0
[1]
Participants in initial and second study registration periods reported separately.
Period Title: Transfer to MD Anderson: 9/19/11-8/28/14
Started 0 [1] 10 0 9
Completed 0 10 0 9
Not Completed 0 0 0 0
[1]
Participants in initial and second study registration periods reported separately.
Arm/Group Title Arm I Lapatinib 1500 mg Arm II Lapatinib 1000 mg Arm III Lapatinib 750 mg Arm IV Placebo Total
Hide Arm/Group Description Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery. Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery. Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery. Placebo orally once daily for 2-6 weeks until the time of surgery. Total of all reporting groups
Overall Number of Baseline Participants 2 10 0 10 22
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2 participants 10 participants 0 participants 10 participants 22 participants
46  (9.5) 51.7  (10.7) 52  (8.4) 51.3  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 10 participants 0 participants 10 participants 22 participants
Female
2
 100.0%
10
 100.0%
10
 100.0%
22
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 10 participants 0 participants 10 participants 22 participants
Hispanic or Latino
0
   0.0%
1
  10.0%
2
  20.0%
3
  13.6%
Not Hispanic or Latino
2
 100.0%
9
  90.0%
8
  80.0%
19
  86.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 10 participants 0 participants 10 participants 22 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
  10.0%
0
   0.0%
1
   4.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
2
 100.0%
9
  90.0%
9
  90.0%
20
  90.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
  10.0%
1
   4.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 2 participants 10 participants 0 participants 10 participants 22 participants
2 10 10 22
1.Primary Outcome
Title Proliferation (Ki67 IHC) in Ductal Breast Carcinoma In Situ (DCIS)
Hide Description 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.
Time Frame 2-6 weeks from baseline to surgery, up to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
No outcome data available due to laboratory issues affecting the analysis of biomarkers results.
Arm/Group Title Arm I Lapatinib 1500 mg Arm II Lapatinib 1000 mg Arm III Lapatinib 750 mg Arm IV Placebo
Hide Arm/Group Description:
Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery.
Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery.
Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery.
Placebo orally once daily for 2-6 weeks until the time of surgery.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Primary Outcome
Title Incidence of Adverse Events Graded According to the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) Version 3.0
Hide Description 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.
Time Frame From baseline to 4-5 weeks after surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I Lapatinib 1500 mg Arm II Lapatinib 1000 mg Arm III Lapatinib 750 mg Arm IV Placebo
Hide Arm/Group Description:
Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery.
Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery.
Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery.
Placebo orally once daily for 2-6 weeks until the time of surgery.
Overall Number of Participants Analyzed 2 10 0 10
Measure Type: Number
Unit of Measure: participants
Grade 3 0 0 1
Grade 2 2 6 3
Grade 1 0 3 4
3.Secondary Outcome
Title Incidence of Ductal Carcinoma in Situ Remaining at Resection
Hide Description 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.
Time Frame 2-6 weeks from baseline to surgery, up to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
DCIS was present at the time of surgery in all patients.
Arm/Group Title Arm I Lapatinib 1500 mg Arm II Lapatinib 1000 mg Arm III Lapatinib 750 mg Arm IV Placebo
Hide Arm/Group Description:
Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery.
Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery.
Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery.
Placebo orally once daily for 2-6 weeks until the time of surgery.
Overall Number of Participants Analyzed 2 10 0 10
Measure Type: Number
Unit of Measure: participants
Present 2 10 10
Absent 0 0 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I Lapatinib 1500 mg, Arm II Lapatinib 1000 mg, Arm III Lapatinib 750 mg, Arm IV Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Biomarker Analysis of Proliferation Markers
Hide Description 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.
Time Frame 2-6 weeks from baseline to surgery, Up to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
No outcome data available due to laboratory issues affecting the analysis of biomarkers results.
Arm/Group Title Arm I Lapatinib 1500 mg Arm II Lapatinib 1000 mg Arm III Lapatinib 750 mg Arm IV Placebo
Hide Arm/Group Description:
Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery.
Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery.
Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery.
Placebo orally once daily for 2-6 weeks until the time of surgery.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Subjects followed up to 4-5 weeks after surgery to assess for adverse events with overall collection period approximately five years, first study period January 2008 to March 2010 and second September 2011 to August 2014.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm I Lapatinib 1500 mg Arm II Lapatinib 1000 mg Arm III Lapatinib 750 mg Arm IV Placebo
Hide Arm/Group Description Lapatinib ditosylate 1500 mg orally once daily for 2-6 weeks until the time of surgery. Lapatinib 1000 mg orally once daily for 2-6 weeks until the time of surgery. Lapatinib 750 mg orally once daily for 2-6 weeks until the time of surgery. Placebo orally once daily for 2-6 weeks until the time of surgery.
All-Cause Mortality
Arm I Lapatinib 1500 mg Arm II Lapatinib 1000 mg Arm III Lapatinib 750 mg Arm IV Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Arm I Lapatinib 1500 mg Arm II Lapatinib 1000 mg Arm III Lapatinib 750 mg Arm IV Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/2 (0.00%)   0/10 (0.00%)   0/0   1/10 (10.00%) 
Infections and infestations         
Infection  1 [1]  0/2 (0.00%)  0/10 (0.00%)  0/0  1/10 (10.00%) 
Vascular disorders         
Hematoma  1  0/2 (0.00%)  0/10 (0.00%)  0/0  1/10 (10.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Infection with normal absolute neutrophil count (ANC) or grade 1 or 2 neutrophils
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm I Lapatinib 1500 mg Arm II Lapatinib 1000 mg Arm III Lapatinib 750 mg Arm IV Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/2 (100.00%)   9/10 (90.00%)   0/0   8/10 (80.00%) 
Blood and lymphatic system disorders         
Lymphatics  1  0/2 (0.00%)  1/10 (10.00%)  0/0  1/10 (10.00%) 
Endocrine disorders         
Hot flashes/flushes  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Gastrointestinal disorders         
Constipation  1  1/2 (50.00%)  1/10 (10.00%)  0/0  1/10 (10.00%) 
Dehydration  1  0/2 (0.00%)  2/10 (20.00%)  0/0  0/10 (0.00%) 
Diarrhea  1  2/2 (100.00%)  7/10 (70.00%)  0/0  2/10 (20.00%) 
Dysphagia (difficulty swallowing)  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Heartburn/dyspepsia  1  1/2 (50.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Mucositis/stomatitis (clinical exam) Oral cavity  1  0/2 (0.00%)  1/10 (10.00%)  0/0  1/10 (10.00%) 
Nausea  1  1/2 (50.00%)  4/10 (40.00%)  0/0  2/10 (20.00%) 
Vomiting  1  1/2 (50.00%)  0/10 (0.00%)  0/0  1/10 (10.00%) 
General disorders         
Constitutional Symptoms  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Fatigue (asthenia, lethargy, malaise)  1  0/2 (0.00%)  2/10 (20.00%)  0/0  1/10 (10.00%) 
Insomnia  1  1/2 (50.00%)  0/10 (0.00%)  0/0  0/10 (0.00%) 
Pain  1  1/2 (50.00%)  3/10 (30.00%)  0/0  2/10 (20.00%) 
Pain -Other  1  0/2 (0.00%)  2/10 (20.00%)  0/0  0/10 (0.00%) 
Immune system disorders         
Allergic reaction/hypersensitivity (including drug fever)  1  0/2 (0.00%)  2/10 (20.00%)  0/0  0/10 (0.00%) 
Infections and infestations         
Infection  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Injury, poisoning and procedural complications         
Cytokine release syndrome/acute infusion reaction  1  0/2 (0.00%)  0/10 (0.00%)  0/0  1/10 (10.00%) 
Metabolism and nutrition disorders         
Bilirubin (hyperbilirubinemia)  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Magnesium, serum-low (hypomagnesemia)  1  0/2 (0.00%)  0/10 (0.00%)  0/0  1/10 (10.00%) 
Nervous system disorders         
Dizziness  1  0/2 (0.00%)  2/10 (20.00%)  0/0  1/10 (10.00%) 
Neuropathy: sensory  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Renal and urinary disorders         
Bladder spasms  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Renal/Genitourinary  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Urinary frequency/urgency  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  1/2 (50.00%)  0/10 (0.00%)  0/0  0/10 (0.00%) 
Pulmonary/Upper Respiratory  1  0/2 (0.00%)  0/10 (0.00%)  0/0  2/10 (20.00%) 
Skin and subcutaneous tissue disorders         
Dermatology/Skin  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Dry skin  1  1/2 (50.00%)  3/10 (30.00%)  0/0  0/10 (0.00%) 
Flushing  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Pruritus/itching  1  1/2 (50.00%)  1/10 (10.00%)  0/0  1/10 (10.00%) 
Rash/desquamation  1  1/2 (50.00%)  3/10 (30.00%)  0/0  2/10 (20.00%) 
Rash: acne/acneiform  1  1/2 (50.00%)  3/10 (30.00%)  0/0  2/10 (20.00%) 
Vascular disorders         
Hemorrhage, GI Rectum  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Hemorrhage, GU Vagina  1  1/2 (50.00%)  0/10 (0.00%)  0/0  0/10 (0.00%) 
Hemorrhage, pulmonary/upper respiratory Nose  1  1/2 (50.00%)  0/10 (0.00%)  0/0  0/10 (0.00%) 
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)  1  0/2 (0.00%)  1/10 (10.00%)  0/0  0/10 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Powel H. Brown, MD/Chair, Clinical Cancer Prevention
Organization: University of Texas (UT) MD Anderson Cancer Center
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00555152     History of Changes
Obsolete Identifiers: NCT00570453
Other Study ID Numbers: NCI-2009-00875
NCI-2009-00875 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2008-0086
CDR0000573719
H-19895
P50CA058183 ( U.S. NIH Grant/Contract )
P30CA016672 ( U.S. NIH Grant/Contract )
First Submitted: November 6, 2007
First Posted: November 7, 2007
Results First Submitted: July 24, 2015
Results First Posted: November 25, 2015
Last Update Posted: April 20, 2018