Clinical trial NCT00499681
Conditions: Breast Cancer
Keywords: stage I breast cancer stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer
Sponsor: Vanderbilt-Ingram Cancer Center
Start date: 2007-07-01; Completion date: 2010-12-01
Enrollment: 6 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving letrozole together with lapatinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This randomized phase II trial is studying how well giving letrozole together with lapatinib works in treating postmenopausal women with stage I, stage II, or stage III breast cancer that can be removed by surgery.

Detailed description:
OBJECTIVES:

Primary

* To determine the pathological complete response in patients with HER2-positive and hormone receptor-positive operable stage I-III breast cancer.

Secondary

* 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.

Arms: arm 1: Patients receive Lapatinib and Letrozole once daily for two weeks, following tumor measurement patients receive Lapatinib and Letrozole once daily for 14 weeks. arm 2: Patients receive Letrozole and placebo once daily for 2 weeks, following tumor measurement patients receive Letrozole and Lapatinib once daily for 14 weeks.
Interventions: intervention 1: lapatinib ditosylate intervention 2: letrozole intervention 3: placebo
Intervention descriptions: intervention 1: Given once daily, 1500mg, for 2 weeks; Given once daily, 1500mg, for 14 weeks in Arm II intervention 2: Given once daily, 2.5mg, for 2 weeks; Given once daily, 2.5mg, for 14 weeks intervention 3: Given once daily for 2 weeks

Protocol documents: