Clinical trial NCT00422903: Letrozole In Combination With Lapatinib In Neoadjuvant Treatment Of Early Breast Cancer
Official title: Letrozole Versus Letrozole Plus Lapatinib (GW572016) in Hormone-sensitive, HER-2 Negative Operable Breast Cancer. A Double Blind Randomized Phase II Study With Biomarker Evaluation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms, Breast
Keywords: neo-adjuvant
letrozole
lapatinib
primary breast cancer
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-01-17
Enrollment: 92
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of Participants With Clinical Objective Response (cOR) in the Breast, Evaluated by an Independent Radiological Evaluation Monitoring Committee
timeFrame: From Baseline (Day 1) up to 6 months, evaluated every 12 weeks
measure: Percentage of Participants With Various Responses in the Breast, Evaluated Using Per Protocol Criteria
timeFrame: From Baseline (Day 1) up to 6 months, evaluated every 12 weeks
Secondary outcomes:
measure: Percentage of Participants With Pathological Complete Response (pCR) in the Breast and Axillary Nodes, Evaluated Using Miller and Payne Criteria
timeFrame: At the point of definitive surgery (up to 6 months after Baseline)
measure: Number of Participants With Breast Tumors Per Pathological Stage at Surgery
timeFrame: At the point of definitive surgery (up to 6 months after Baseline)
measure: Number of Participants With the Indicated Nodal Status at Surgery
timeFrame: At the point of definitive surgery (up to 6 months after Baseline)
measure: Number of Participants With the Indicated Type of Surgery
timeFrame: At the point of definitive surgery (up to 6 months after Baseline 1)
measure: Percentage of Participants With Conversion From Planned Mastectomy at Baseline to BCS at Surgery
timeFrame: At the point of definitive surgery (up to 6 months after Baseline)
measure: Number of Participants With the Indicated Adverse Events With a Classification of >=Grade 2
timeFrame: From Baseline (Day 1) up to 6 months (until definitive surgery)
measure: Mean Left Ventricular Ejection Fraction (LVEF)
timeFrame: Baseline (Day 1), after 12 weeks, and after 24 weeks
measure: Time to Treatment Failure From the Start of the Primary Therapy
timeFrame: From Baseline (Day 1) up to study withdrawal (approx. 66 months)
Other outcomes:
Locations:
city: Carpi (MO)
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Forlì
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Modena
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Piacenza
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Rimini
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Treviglio (BG)
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Brindisi
country: Italy
facility: GSK Investigational Site
state: Puglia
city: Pisa
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Chieti
country: Italy
facility: GSK Investigational Site
city: Cremona
country: Italy
facility: GSK Investigational Site
city: Perugia
country: Italy
facility: GSK Investigational Site
city: Reggio Emilia
country: Italy
facility: GSK Investigational Site
city: Varese
country: Italy
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: