PhII Neo-Adjuvant Letrozole & Lapatinib in Pts w/HER2+ & Hormone Receptor+ Operable Breast CA SPORE

This study has been terminated.
(slow accrual)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Ingrid Mayer, MD, Vanderbilt-Ingram Cancer Center Identifier:
First received: July 10, 2007
Last updated: August 7, 2012
Last verified: August 2012

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.

Condition Intervention Phase
Breast Cancer
Drug: lapatinib ditosylate
Drug: letrozole
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Number of Participants With a Pathological Complete Response [ Time Frame: at 14 weeks ] [ Designated as safety issue: No ]
    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.

Enrollment: 6
Study Start Date: July 2007
Study Completion Date: December 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive Lapatinib and Letrozole once daily for two weeks, following tumor measurement patients receive Lapatinib and Letrozole once daily for 14 weeks.
Drug: lapatinib ditosylate
Given once daily, 1500mg, for 2 weeks; Given once daily, 1500mg, for 14 weeks in Arm II
Other Name: GW572016
Drug: letrozole
Given once daily, 2.5mg, for 2 weeks; Given once daily, 2.5mg, for 14 weeks
Other Name: Femara
Experimental: Arm II
Patients receive Letrozole and placebo once daily for 2 weeks, following tumor measurement patients receive Letrozole and Lapatinib once daily for 14 weeks.
Drug: lapatinib ditosylate
Given once daily, 1500mg, for 2 weeks; Given once daily, 1500mg, for 14 weeks in Arm II
Other Name: GW572016
Drug: letrozole
Given once daily, 2.5mg, for 2 weeks; Given once daily, 2.5mg, for 14 weeks
Other Name: Femara
Other: placebo
Given once daily for 2 weeks
Other Name: placebo

Detailed Description:



  • 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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No


Inclusion Criteria:

  • Clinical stage I, II, or III operable invasive mammary carcinoma, confirmed by histological analysis

    • Measurable residual tumor at the primary site

      • Measurable disease is defined as any mass that can be reproducibly measured by physical examination, mammogram, and/or ultrasound and can be accurately measured in at least one dimension (longest diameter to be recorded) as 10 mm (1 cm)
  • Available core biopsies from the time of diagnosis

    • May include sections of paraffin-embedded material
  • Scheduled to undergo surgical treatment with either segmental resection or total mastectomy
  • Prior history of contralateral breast cancer allowed if patient has no evidence of recurrence of their initial primary breast cancer within the last 5 years
  • HER2-positive by Herceptest (3+) or FISH
  • ER-positive and/or PR-positive by IHC

Exclusion Criteria:

  • Locally recurrent breast cancer
  • Evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases)


Inclusion Criteria:

  • Female
  • Postmenopausal, as defined by any of the following:

    • At least 55 years of age
    • Under 55 years of age and amenorrheic for at least 12 months OR follicle-stimulating hormone (FSH) values ≥ 40 IU/L and estradiol levels ≤ 20 IU/L
    • Prior bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months
  • ECOG performance status 0-1
  • ANC ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • AST and ALT ≤ 1.5 times ULN
  • Able to swallow and retain oral medication
  • Cardiac ejection fraction normal by echocardiogram (or MUGA scan if an echocardiogram cannot be performed or is inconclusive)

Exclusion Criteria:

  • Premenopausal breast cancer, pregnant, or lactating
  • Serious medical illness, that in the judgment of the treating physician, places the patient at high risk of operative mortality
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
  • Ulcerative colitis
  • History of other malignancy

    • Patients who have been disease-free for 5 years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinomas are eligible
  • Active or uncontrolled infection
  • Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure


Exclusion Criteria:

  • Prior chemotherapy for primary breast cancer
  • Tamoxifen or raloxifene as a preventive agent within the past 21 days
  • Hormone replacement therapy (e.g., conjugated estrogens tablets [Premarin]) within the past month
  • Prior therapy with anthracyclines
  • Investigational drug within the past 30 days or 5 half-lives, whichever is longer
  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, or any other biologic therapy) other than letrozole
  • Concurrent treatment with an investigational agent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00499681

United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, United States, 37064
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
Study Chair: Ingrid Mayer, MD Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: Ingrid Mayer, MD, Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist, Vanderbilt-Ingram Cancer Center Identifier: NCT00499681     History of Changes
Other Study ID Numbers: VICC BRE 0660, VU-VICC-BRE-0660, VU-VICC-061102, GSK-LAP107087
Study First Received: July 10, 2007
Results First Received: October 17, 2011
Last Updated: August 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt-Ingram Cancer Center:
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses processed this record on October 09, 2015