A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Study Comparing GW572016 and Letrozole Versus Letrozole in Subjects With Estrogen/Progesterone Receptor- Positive Advanced or Metastatic Breast Cancer
Lapatinib
+ Letrozole
+ Placebo
Breast Diseases+2
+ Breast Neoplasms
+ Neoplasms
Treatment Study
Summary
Study start date: December 9, 2003
Actual date on which the first participant was enrolled.Subjects were randomly assigned to receive either lapatinib (1500 mg once daily orally) with letrozole (2.5 mg once daily orally), or letrozole (2.5 mg once daily orally) with placebo (which matched with lapatinib tablet). Randomization was stratified by site of disease (i.e., soft tissue/visceral disease versus bone only disease) and time since prior adjuvant endocrine therapy (<6 months or ≥ 6 months from discontinuation of adjuvant anti-estrogen therapy (e.g. tamoxifen or raloxifene) or no prior adjuvant antiestrogen therapy). Study therapy was administered daily until disease progression (objective or symptomatic) or withdrawal from therapy (e.g., due to unacceptable toxicity, withdrawal of consent, or other reason). All subjects were to be followed for survival information until death. On 13 Apr 2015, after the introduction of the Long Term Follow UP (LTFU) phase (per protocol amendment 07), subjects receiving study treatment with lapatinib plus letrozole, or letrozole plus placebo had continued access to this study treatment until the occurrence of one of the following criteria: * Disease progression (as determined by the Investigator), * Intercurrent illness that prevented further administration of study treatment * Drug related AE which was considered by the investigator to warrant permanent discontinuation of study treatment * The subject decided to withdraw from the study. Investigators collected AEs and/or SAEs related to study participation, until 30 days following study treatment discontinuation. Subjects who were being followed-up for OS but were not taking study medication, were withdrawn from the study. The study was terminated on 22-Mar-2018 (last subject last visit).
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.1286 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Female
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Key inclusion criteria 1. Signed informed consent; 2. Subjects with histologically confirmed invasive breast cancer with stage IV disease at primary diagnosis or at relapse after curative-intent surgery; * Subjects with either measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST). * If the disease was restricted to a solitary lesion, its neoplastic nature was confirmed by cytology or histology. 3. Tumors that were ER+ and/or PgR+; 4. Post-menopausal female subjects ≥ 18 years of age. 5. ECOG Performance Status of 0 or 1; 6. Subjects who had archived tumor tissue available to compare tumor response with intra-tumoral expression of ErbB1 and ErbB2. 7. Adjuvant therapy with an aromatase inhibitor and / or trastuzumab was allowed; however, treatment was to stop more than 1 year prior (\>12 months) to the first dose of randomized therapy. 8. Subjects must have ended hormonal replacement therapy (HRT) at least 1 month (30 days) prior to receiving the first dose of randomized therapy. Key exclusion criteria: 1. Pre-menopausal, pregnant, or lactating; 2. Received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for advanced or metastatic disease; 3. Bisphosphonate therapy for bone metastases was allowed; however, treatment was to be initiated prior to the first dose of randomized therapy. Prophylactic use of bisphosphonates in subjects without bone disease, except for the treatment of osteoporosis, was not permitted; 4. Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of randomized therapy (lapatinib or placebo); 5. Subjects with known history of/clinical evidence of CNS metastases or leptomeningeal carcinomatosis; and / or subjects on concurrent anti-cancer therapies other than letrozole; and / or who have not recovered from toxicities related to prior adjuvant therapy (surgery, radiotherapy, chemotherapy etc.) 6. Subjects with active or uncontrolled infection and/ or with history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure.
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.2 intervention groups are designated in this study
50% chance of being blinded to the placebo group
Treatment Groups
Group I
ExperimentalGroup II
PlaceboStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 278 locations
Novartis Investigative Site
Lille Cedex, FranceNovartis Investigative Site
Montpellier, FranceNovartis Investigative Site
Paris Cedex 5, France