A Multicenter, Open Label, Randomized Phase II Trial of Presurgical Treatment With Single-Agent Trastuzumab (H) or Lapatinib (Ty) or the Combination of Trastuzumab and Lapatinib (H+Ty), Followed by Six Cycles of Docetaxel (T) and Carboplatin (C) With Trastuzumab (TCH) or Lapatinib (TCTy) or the Combination of Trastuzumab and Lapatinib (TCHTy) in Patients With HER2/Neu-Amplified Operable Breast Cancer
- To investigate the clinical efficacy of neoadjuvant docetaxel and carboplatin in
combination with trastuzumab (Herceptin®) and/or lapatinib ditosylate by estimating the
pathologic complete response (pCR) rate in the breast and axilla of women with
HER2/neu-positive resectable stage I-III adenocarcinoma of the breast.
- To estimate the molecular effects of lapatinib ditosylate and trastuzumab alone or in
combination on tumor tissues of these patients by assessing changes in gene expression
using serial gene microarray analysis.
- To assess for gene expression and/or biomarker changes that may be correlated with or
predict pCR and clinical response to lapatinib ditosylate and/or trastuzumab in these
- To evaluate the safety and tolerability of these regimens in these patients.
- To evaluate the clinical efficacy of these regimens by estimating the clinical
objective response rate (complete response and partial response) in these patients.
- To estimate the rate of congestive heart failure or drop in LVEF (> 10% points from
baseline and below lower limits of normal) in each of the three treatment arms.
OUTLINE: This is a multicenter study. Patients are stratified according to baseline tumor
size (≤ 3 cm vs > 3 cm) and hormone receptor status (estrogen receptor [ER]- and/or
progesterone receptor [PR]-positive vs ER- and PR- negative). Patients are randomized to 1
of 3 treatment arms.
- Arm I: Patients receive a trastuzumab IV over 90 minutes on day 1 in course 1. Patients
receive docetaxel IV, carboplatin IV, and trastuzumab IV over 30 minutes on day 1 in
courses 2-7. Courses repeat every 21 days in the absence of disease progression or
- Arm II: Patients receive oral lapatinib ditosylate once daily on days 1-21 in course 1.
Patients receive docetaxel IV, carboplatin IV as in arm I and oral lapatinib ditosylate
once daily on days 1-21 in courses 2-7. Courses repeat every 21 days in the absence of
disease progression or unacceptable toxicity.
- Arm III: Patients receive trastuzumab IV as in arm I on day 1 and oral lapatinib
ditosylate as in arm II on days 1-21 in course 1. Patients receive docetaxel IV,
carboplatin IV, and trastuzumab IV as in arm I on day 1 and oral lapatinib ditosylate
as in arm II on days 1-21 in courses 2-7. Courses repeat every 21 days in the absence
of disease progression or unacceptable toxicity.
Within 4-6 weeks after completion of chemotherapy, all patients under go definitive surgery
and/or radiotherapy at the discretion of the treating physician. Tumor biopsy and blood
samples are collected for biomarker analysis and molecular analysis at baseline, after
course 1, and at the time of definitive breast surgery or completion of chemotherapy. Gene
expression changes are analyzed by mRNA microarray analysis and molecular changes in protein
expression profiles by IHC. Samples may also be analyzed by RT-PCR.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Pathologic complete response (pCR)
Sara Hurvitz, MD
Jonsson Comprehensive Cancer Center
United States: Food and Drug Administration
|Florida Hospital Cancer Institute||Orlando, Florida 32804|
|Comprehensive Blood and Cancer Center||Bakersfield, California 93309|
|Sansum Medical Clinic||Santa Barbara, California 93105|
|Wilshire Oncology Medical Group, Incorporated - Pomona||Pomona, California 91767-3021|
|Santa Barbara Hematology Oncology - Solvang||Solvang, California 93463|
|North Valley Hematology-Oncology Medical Group||Mission Hills, California 91345|
|New Mexico Cancer Center||Albuquerque, New Mexico 87109|
|Central Coast Medical Oncology Corporation||Santa Maria, California 93454|
|Providence Medical Group||Terre Haute, Indiana 47802|
|Central Hematology Oncology Medical Group, Incorporated - Alhambra||Alhambra, California 91801|
|St. Jude Heritage Medical Group at Virginia K. Crosson Cancer Center||Fullerton, California 92835|
|Cancer Care Associates Medical Group, Incorporated - Redondo Beach||Torrance, California 90505|
|Cancer Institute of Florida, PA - Orlando||Orlando, Florida 32804|
|Hematology and Oncology Consultants, PA - Orlando||Orlando, Florida 32804|
|Comprehensive Cancer Centers of Nevada - Henderson||Henderson, Nevada 89052|