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

Phase 2

Completed

• Conditions: Neoplasms, Breast
• Interventions: Drug: letrozole; Drug: lapatinib; Other: placebo

• Registration Number: NCT00422903
• Lead Sponsor: GlaxoSmithKline

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2007-01-16
• Study First Submitted QC: 2007-01-16
• Study First Posted: 2007-01-17
• Study Start: 2007-04
• Primary Completion: 2011-04
• Study Completion: 2011-04
• Results First Submitted: 2012-04-06
• Results First Submitted QC: 2012-07-26
• Results First Posted: 2012-08-29
• Status Verified: 2016-03
• Last Update Submitted: 2016-04-07
• Last Update Posted: 2016-05-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 92

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Letrozole plus placebo	letrozole	Letrozole 2.5 mg administered orally fro 6 mos. plus placebo 1500 mg administered orally throughout the study until definitive surgery
Letrozole plus placebo	placebo	Letrozole 2.5 mg administered orally fro 6 mos. plus placebo 1500 mg administered orally throughout the study until definitive surgery
Letrozole plus lapatininb	lapatinib	Letrozole 2.5 mg administered orally fro 6 mos. plus lapatinib 1500 mg administered orally throughout the study until definitive surgery
Letrozole plus lapatininb	letrozole	Letrozole 2.5 mg administered orally fro 6 mos. plus lapatinib 1500 mg administered orally throughout the study until definitive surgery

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Clinical Objective Response (cOR) in the Breast, Evaluated by an Independent Radiological Evaluation Monitoring Committee	From Baseline (Day 1) up to 6 months, evaluated every 12 weeks	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.
Percentage of Participants With Various Responses in the Breast, Evaluated Using Per Protocol Criteria	From Baseline (Day 1) up to 6 months, evaluated every 12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Pathological Complete Response (pCR) in the Breast and Axillary Nodes, Evaluated Using Miller and Payne Criteria	At the point of definitive surgery (up to 6 months after Baseline)	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.
Percentage of Participants With Conversion From Planned Mastectomy at Baseline to BCS at Surgery	At the point of definitive surgery (up to 6 months after Baseline)	The percentage of participants who were planned to undergo a mastectomy at baseline but later underwent BCS was measured.
Number of Participants With the Indicated Adverse Events With a Classification of >=Grade 2	From Baseline (Day 1) up to 6 months (until definitive surgery)	Toxicity was measured in grades (severity of the AE) as per National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI CTCAE) version (v) 3.0. The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening/disabling; Grade 5, death related to the AE. Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, and hypertension is high blood pressure.
Mean Left Ventricular Ejection Fraction (LVEF)	Baseline (Day 1), after 12 weeks, and after 24 weeks	Cardiac safety was evaluated as any signs or symptoms of deterioration in LVEF. LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. LVEF was evaluated using NCI CTCAE.
Time to Treatment Failure From the Start of the Primary Therapy	From Baseline (Day 1) up to study withdrawal (approx. 66 months)	Time to treatment failure is calculated as the interval between the date of randomization and the occurrence of local tumor progression (including ipsilateral \[on the same side\] and controlateral breast tumor progression), distant tumor progression, permanent treatment discontinuation (either for the experimental or conventional treatment arm), or death for any cause.
Number of Participants With Breast Tumors Per Pathological Stage at Surgery	At the point of definitive surgery (up to 6 months after Baseline)	Tumors were categorized as follows: T0, no evidence of primary tumor, but carcinoma of the milk ducts, accumulation of abnormal cells in the breast lobules, or Paget disease (cancer condition that appears like a skin disease involving the breast nipple) with no associated tumor mass; T1, tumor was \<=2 centimeters (cm) across; T2, tumor was \>2 cm but \<5 cm across; T3, tumor was \>5 cm across; T4, tumor of any size growing into the chest wall or skin, including inflammatory breast cancer.
Number of Participants With the Indicated Nodal Status at Surgery	At the point of definitive surgery (up to 6 months after Baseline)	The nodal status of cancer indicates the involvement of lymph nodes in the participant with cancer. N0 indicates no involvement of lymph nodes, and N+ indicates involvement of lymph nodes.
Number of Participants With the Indicated Type of Surgery	At the point of definitive surgery (up to 6 months after Baseline 1)	Mastectomy is the medical term for the surgical removal of one or both breasts. Breast-conserving surgery (BCS) involves removing only the affected part of the breast tissue during surgery, as opposed to removal of the entire breast.

Trial Locations

Locations (1)

GSK Investigational Site; 🇪🇸 Badalona, Spain