Lapatinib Ditosylate in Treating Patients With Ductal Breast Carcinoma In Situ

NCT00555152 | Completed Results DMC

• 7 other identifiers: NCI-2009-008752008-0086NCT00570453CDR0000573719H-19895P50CA058183P30CA016672
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Ductal Breast Carcinoma In Situ; HER2/Neu Positive

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  From baseline to 4-5 weeks after surgery

Secondary Outcomes (2)

• Incidence of Ductal Carcinoma in Situ Remaining at Resection

  2-6 weeks from baseline to surgery, up to 6 weeks

• Biomarker Analysis of Proliferation Markers

  2-6 weeks from baseline to surgery, Up to 6 weeks

Study Arms (2)

Arm I (lapatinib ditosylate)

EXPERIMENTAL

Patients receive lapatinib ditosylate PO once QD for 2-6 weeks until the time of surgery.

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.

Other: Laboratory Biomarker Analysis; Other: Placebo

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (lapatinib ditosylate); Arm II (placebo)

Lapatinib Ditosylate DRUG

Given PO

Also known as: Tykerb

Arm I (lapatinib ditosylate)

Placebo OTHER

Given PO

Also known as: placebo therapy, PLCB, sham therapy

Arm II (placebo)

Eligibility Criteria

• Age: 21 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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%

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Powel H. Brown, MD/Chair, Clinical Cancer Prevention
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

Study Officials

• Powel Brown

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2007
• First Posted: November 7, 2007
• Study Start: August 19, 2009
• Primary Completion: August 28, 2014
• Study Completion: August 28, 2014
• Last Updated: April 20, 2018
• Results First Posted: November 25, 2015

Record last verified: 2018-03

Locations

US (2)