Lapatinib Ditosylate, Trastuzumab, Paclitaxel, and Surgery in Treating Patients With Breast Cancer

NCT01688609 | Completed Phase 2 Results

• 4 other identifiers: NCI-2012-01970CDR0000734375ACE-0019020
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 3

Brief Summary

This phase II trial studies how well giving lapatinib ditosylate together with trastuzumab, paclitaxel, and surgery works in treating patients with breast cancer. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Conditions

HER2-positive Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks

  For biomarkers ALDH1 and CD44v, the change in the proportions of CD44v-positive (CD44v+) tumor cells and ALDH1-positive (ALDH1+) tumor cells in tumor tissue from baseline to 6 weeks and 18 weeks time points were determined for each patient. For biomarker change, changes in the binary biomarkers between time points were assessed using McNemar's test in all patients and separately in patients with and without pCR.

  From baseline to 18 weeks

• Number of Participants With Pathological Complete Response (pCR)

  The point estimate of the pCR rate will be calculated for all patients. pCR is defined as the abscence of invasive cancer in the breast and regional lymph nodes following neoadjuvant chemotherapy.

  Up to 12 weeks

Secondary Outcomes (3)

• Cellular Response Rate, Defined as Patients With an Epithelial Phenotype Having Eradication of CTCs; Patients With a Mesenchymal Phenotype Having Eradication of Tumor Cells; Patients With a Mesenchymal Phenotype Converting to an Epithelial Phenotype

  Up to 18 weeks

• EGFR-mutation Status of Tumors and Changes in the Ratio of Phosphorylated to Nonphosphorylated HER2, EGFR, ERK, Akt, and the Ki67 and TUNEL Indices Before and After Treatment

  From baseline to 24 weeks

• Number of Participants With Treatment-Related Toxicities

  Up to 12 weeks after completion of study treatment

Study Arms (1)

Treatment (lapatinib, trastuzumab, paclitaxel, surgery)

EXPERIMENTAL

Drug exposure: Patients receive lapatinib ditosylate PO QD and trastuzumab IV over 30-90 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Preoperative therapy: Patients receive lapatinib ditosylate PO QD, trastuzumab IV over 30 minutes once weekly, and paclitaxel IV over 90 minutes once weekly for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo lumpectomy or mastectomy.

Drug: lapatinib ditosylate; Drug: paclitaxel; Biological: trastuzumab; Procedure: therapeutic conventional surgery; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

lapatinib ditosylate DRUG

Given PO

Also known as: GSK572016, GW-572016, GW2016, Lapatinib, Tykerb

Treatment (lapatinib, trastuzumab, paclitaxel, surgery)

paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol

Treatment (lapatinib, trastuzumab, paclitaxel, surgery)

trastuzumab BIOLOGICAL

Given IV

Also known as: anti-c-erB-2, Herceptin, MOAB HER2

Treatment (lapatinib, trastuzumab, paclitaxel, surgery)

therapeutic conventional surgery PROCEDURE

Undergo lumpectomy or mastectomy

Treatment (lapatinib, trastuzumab, paclitaxel, surgery)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (lapatinib, trastuzumab, paclitaxel, surgery)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (lapatinib, trastuzumab, paclitaxel, surgery)

Eligibility Criteria

• Age: 20 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed primary invasive breast cancer
• Primary tumor is larger than 2 cm in diameter (T2) as measured by caliper or ultrasound
• Overexpression and/or amplification of HER2 is confirmed by immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) + when IHC 2+
• Patients have not received prior therapies for breast cancer
• Patients have Karnofsky \>= 70%
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Hemoglobin \>= 9.0 g/dL
• Platelets \>= 75,000/mcL
• Total bilirubin =\< 1.5 times institutional upper limit of normal
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase\[SGPT\]) =\< 2.5 times institutional ULN
• Creatinine =\< 1.5 times institutional upper limit of normal (ULN)
• Patients must have left ventricular ejection fraction (LVEF) \>= 50% by multi-gated acquisition (MUGA) or echocardiography
• Patients must be able to take oral medications (i.e., no uncontrolled vomiting, inability to swallow, or diagnosis of chronic malabsorption)
• Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation as well as for at least 6 months after the last dose of trastuzumab

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy
• Patients who are receiving any other investigational agents
• Patients have distal metastasis (stage IV disease)
• Patients with previous (within 10 years) or current history of malignant neoplasm except for curatively treated basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or other agents used in study
• Patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) are ineligible
• Patients who have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women
• Patients who have family or personal history of congenital long or short QT syndrome, Brugada syndrome, QT/QTc prolongation, or torsade de pointes
• Patients who have chronic gastrointestinal disease presenting with diarrhea (inflammatory bowel disease, malabsorption, or \>= grade 2 diarrhea of any etiology at baseline)
• Patients who have neuropathy \>= grade 2 of any cause
• Patients are diagnosed with inflammatory breast cancer or bilateral breast cancer

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Keio University

Shinjuku-ku, Tokyo, 160-8582, Japan

Location

Saint Luke's International Hospital

Chūōku, Toyko, 104-8560, Japan

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl-6-(5-((methylsulfonyl)ethyl)aminomethyl)-2-furyl)-4-quinazolinamine; Paclitaxel; Taxes; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Teruo Yamauchi
• Organization: St. Luke's International Hospital

tryhi@luke.ac.jp

+81-3-3541-5151

Study Officials

• Teruo Yamauchi

  Saint Luke's International Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2012
• First Posted: September 20, 2012
• Study Start: July 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: August 15, 2016
• Last Updated: September 11, 2017
• Results First Posted: September 11, 2017

Record last verified: 2017-08

Locations

US (1); JP (2)