A Phase II Neo-Adjuvant Study of Letrozole in Combination With Lapatinib in Post -Menopausal Patients With HER2-Positive and Hormone Receptor-Positive Operable Breast Cancer
- To determine the pathological complete response in patients with HER2-positive and
hormone receptor-positive operable stage I-III breast cancer.
- To determine tumor cell apoptosis in situ as measured by TUNEL analysis of tumor
sections from fresh frozen or paraffin-embedded core biopsies. (Parts 1 and 2)
- To determine whether EGFR, P-EGFR, P-HER2, Ser118 P-ERα, P-Akt, and P-MAPK (by IHC
using fresh frozen or paraffin-embedded core biopsies) predict the inhibition of
proliferation in situ (Ki67) and/or induction of cell death (TUNEL). (Parts 1 and 2)
- To determine the safety profile of neoadjuvant letrozole and lapatinib. (Part 2)
- To evaluate tumor response to treatment as measured by ultrasound. (Part 2)
- To evaluate the rate of breast conservation surgery. (Part 2)
- To determine the inhibition in cell proliferation in situ in response to letrozole and
lapatinib as measured by the change in percentage of Ki67-positive tumor cells
(determined by IHC using tumor sections from fresh frozen or paraffin-embedded surgical
material). (Part 2)
OUTLINE: This is a randomized, double-blind, placebo-controlled, two-part study.
- Part 1: Patients are randomized to treatment arm.
- Patients receive lapatinib and letrozole once daily for 2 weeks.
- Patients receive letrozole and placebo once daily for 2 weeks. Patients then
proceed to part 2.
- Part 2: All patients receive lapatinib and letrozole once daily for 14 weeks. Patients
then undergo surgical resection of disease.
Patients undergo tissue sample collection at baseline, at 2 weeks, and then at the time of
surgery for biomarker and laboratory studies. Samples are analyzed by IHC and TUNEL.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Number of Participants With a Pathological Complete Response
Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
at 14 weeks
Ingrid Mayer, MD
Vanderbilt-Ingram Cancer Center
United States: Food and Drug Administration
VICC BRE 0660
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|Vanderbilt-Ingram Cancer Center - Cool Springs||Nashville, Tennessee 37064|
|Vanderbilt-Ingram Cancer Center at Franklin||Nashville, Tennessee 37064|