Letrozole In Combination With Lapatinib In Neoadjuvant Treatment Of Early Breast Cancer

GlaxoSmithKline92 enrolled

Overview

Evaluate the percentage of clinical objective responses (cOR) in patients with HER2 negative early breast cancer treated with pre operative (neoadjuvant)lapatinib and letrozole

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Neoplasms, Breast

Interventions

lapatinibDRUG

1500 mg administered orally daily

letrozoleDRUG

2.5 mg administered orally daily

placeboOTHER

1500 mg administered orally daily

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion criteria: * Histologically confirmed infiltrating primary breast cancer of 2.0 cm or more in largest clinical diameter * ER and/or PgR positive cancer (\> 10% of positive cancer cell assessed by IHC) * Postmenopausal status, defined by at least one of the following: ≥ 60 years of age \< 60 years of age and amenorrheic for ≥ 12 months prior to day 1 \< 60 years of age and amenorrheic for \< 12 months prior to day, or without a uterus: luteinizing hormone (LH) and follicle stimulating hormone (FSH) values within postmenopausal range Prior bilateral oophorectomy Prior radiation castration with amenorrhea for at least 6 months * HER2 negative tumors (IHC 0-2+, or FISH negative) * Availability of tumor tissue suitable for biological and molecular examination before starting primary treatment * Age over 18 years * ECOG PS 0-1 * Normal organ and marrow function as defined below: leukocytes \> 3000/mL absolute neutrophil count \> 1,500/mL platelets \> 100,000/mL total bilirubin within normal institutional limits AST (SGOT)/ALT(SGPT)\< 2.5 X institutional upper limit of normal Creatinine within normal institutional limits * Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan. * Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of lapatinib will be determined following review of their use by the Principal Investigator. A list of medications and substances known or with the potential to interact with CYP450 isoenzymes is provided * Ability to understand and the willingness to sign a written informed consent document. * Ability to swallow and retain oral medication. Exclusion criteria: * Stage IIIB, IIIC, and inflammatory breast cancer * Stage IV breast cancer * Contraindication to the treatment with letrozole * Prior treatment with chemotherapy, endocrine therapy or radiotherapy. Prior treatment with EGFR targeting therapies * Treatment with any other investigational agents, or with all herbal (alternative) medicines * History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib * Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * HIV-positive patients receiving combination anti-retroviral therapy * GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis) * Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors (See section 3.7.4.2 Other concomitant treatments)

Locations (14)

GSK Investigational Site

Brindisi, Apulia, Italy

GSK Investigational Site

Carpi (MO), Emilia-Romagna, Italy

GSK Investigational Site

Forlì, Emilia-Romagna, Italy

Outcomes

Primary Outcomes

Percentage of Participants With Clinical Objective Response (cOR) in the Breast, Evaluated by an Independent Radiological Evaluation Monitoring Committee

cOR is defined as the documented evidence of complete response (CR) and partial response (PR) as assessed by ultrasound examination using Response Evaluation Criteria In Solid Tumors (RECIST). CR is defined as the disappearance of all target lesions (TLs) and non-TLs and the appearance of no new lesions (NLs). PR for TLs is defined as a \>=30% decrease in the sum of the longest diameter (LD) of TLs, taking as a reference the Baseline sum LD. For non-TLs, it is defined as the persistence of \>=1 non-TL and no new TLs or non-TLs.

Time frame: From Baseline (Day 1) up to 6 months, evaluated every 12 weeks

Percentage of Participants With Various Responses in the Breast, Evaluated Using Per Protocol Criteria

Complete clinical response=nodule not detectable; all ultrasound abnormalities detected at diagnosis have disappeared. Partial clinical response=the tumor's longest diameter (LD) is reduced by 50% or more; ultrasound characteristics of the tumor persist. Minimal response=the tumor's LD is reduced by 25%-49%. Stable disease=the tumor's LD is decreased by less than 25% and is increased by no more than 25% from the starting value. Progressive disease=the tumor's LD is increased by more than 25% from the starting value. Participants who were not evaluable did not have data available.

Time frame: From Baseline (Day 1) up to 6 months, evaluated every 12 weeks

Secondary Outcomes

Percentage of Participants With Pathological Complete Response (pCR) in the Breast and Axillary Nodes, Evaluated Using Miller and Payne Criteria

pCR is defined as the complete absence of infiltrating tumor cells (TCs) in the breast and lymph nodes. Miller and Payne criteria: Grade 1, no change/some alteration to individual malignant cells, but no reduction in overall cellularity; Grade 2, up to a 30% loss in TCs; Grade 3, between an estimated 30% and 90% reduction in TCs; Grade 4, more than a 90% reduction in TCs, only small cluster/dispersed cells remaining; Grade 5, no malignant identifiable cells; carcinoma in the milk ducts may be present. Grades 1 and 2 = No response; Grades 3 and 4= PR; Grade 5 = CR.

Data from ClinicalTrials.gov

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