Neoadjuvant Combined Endocrine and HER2 Target Therapy in Postmenopausal Women With ER and Her2 Positive Breast Cancer (Neo-All-In)

Neoadjuvant Letrozole and Lapatinib in Postmenopausal Women With ER and Her2 Positive Breast Cancer

Cross-talk between epidermal growth factors and the ER occurs at multiple levels and seems to play a crucial role in breast cancer progression and endocrine resistance.Combined HER1/HER2-targeted therapy with aromatase inhibitors for ER-positive and HER-2 positive postmenopausal breast cancer might enhance response and block emergence of endocrine resistant tumor.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Letrozole, Lapatinib

Detailed Description

1. To evaluate the efficacy of the neoadjuvant combination therapy with letrozole and lapatinib in postmenopausal patients with ER-positive and HER2-positive breast cancer.
2. To assess markers predictive of treatment response and outcome in this setting.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Nedical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Written informed consent
• Female patients
• Histologically confirmed invasive breast cancer
• Primary tumor greater than 2cm diameter, measured by sonography
• N0-3 (any N if resectable) and no evidence of distant metastasis (M) (isolated supraclavicular node involvement allowed)
• ER positive (intermediate and strong positive)
• HER2 positive (IHC3+ or FISH positive in case of IHC 2+)
• No evidence of metastasis (M0)
• No prior hormonal, chemotherapy or radiotherapy is allowed
• No breast operation other than biopsy to make diagnosis is allowed
• Postmenopausal women with ECOG Performance Status of 0 or 1
• 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 ≥ 30 IU/L and estradiol levels ≤ 20 IU/L
• Prior bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months
• Adequate hematopoietic, renal, hepatic function:

Exclusion Criteria:

• Patients who received hormonal, chemotherapy or radiotherapy for breast cancer
• Patients who underwent surgery for breast cancer
• Patients with bilateral invasive breast cancer
• Patients with inflammatory breast cancer (T4d)
• Patients without primary tumor (T0) Inability to perform [18F]FES PET imaging due to physical inability, claustrophobia, or other mental illness.
• ER poor disease as defined locally (e.g: Allred score 1-3, H-score<100)
• Patients who have history of cancer other than in situ uterine cervix cancer or non-melanotic skin cancer
• Chronic daily treatment with aspirin (>325mg/day) or clopidogrel (>75mg/day)
• Chronic daily treatment with corticosteroids (dose of >10mg /day ethylprednisolone equivalent)
• Clinically significant cardiovascular disease: CVA/stroke (<6month prior to enroll), MI (<6month prior to enroll), unstable angina, NYHA Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication.
• Hormone replacement therapy within 4 weeks of starting treatment
• Known hypersensitivity to any of the study drugs including ditosylate monohydrate salt
• Pregnant or nursing mother (if applicable)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Letrozole, Lapatinib; Letrozole 2.5mg po qd + Lapatinib 1500mg po qd for 18-21 wks	Drug: Letrozole, Lapatinib; Letrozole 2.5mg po qd+ Lapatinib 1500mg po qd for 18-21 wks; Other Names: Tykerb; Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	To evaluate the pathologic complete response (pCR) rate to lapatinib combined with letrozole in neoadjuvant setting	2010 Nov- 2012 May

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SUV for [18F]FES PET	To evaluate clinical overall response (cORR) rate, disease free survival (DFS), overall survival (OS); To assess tolerability and QOL; To assess MRI response rate; To identify biological predictors of response to lapatinib combined letrozole treatment; To determine the correlation of [18F]FES PET with biological and imaging predictors of response to the combined modalities; To evaluate the diagnostic value of SUV for [18F]FES PET in the prediction of pathologic, clinical response to neoadjuvant HER2 target- and endocrine therapy	2010 Nov- 2012 May

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Principal Investigator: Sung-Bae Kim, MD, Asan Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): April 1, 2014
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: January 12, 2011
• First Submitted That Met QC Criteria: January 12, 2011
• First Posted (ESTIMATE): January 13, 2011

Study Record Updates

• Last Update Posted (ACTUAL): August 29, 2017
• Last Update Submitted That Met QC Criteria: August 26, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Neoadjuvant; Lapatinib; Postmenopausal; Letrozole
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Lapatinib
• Other Study ID Numbers: 2009-0729