Lapatinib In Chemotherapy-Naive Or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This phase II study will evaluate and compare the efficacy and tolerability of two dose schedules (1500 mg QD and 500 mg BID) of oral Lapatinib as treatment for patients with advanced or metastatic breast cancer.

Official Title
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A Phase II, Open-Label, Randomized, Parallel-Group Multicenter Trial Comparing Two Schedules of GW572016 as First-Line Monotherapy in Patients With Advanced or Metastatic Breast Cancer

Conditions
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Neoplasms, Breast

Intervention / Treatment
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* Drug: Lapatinib


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically confirmed invasive breast cancer with incurable stage IIIB, IIIC with T4 lesion or stage IV disease at primary diagnosis or at relapse after curative intent surgery. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Documented amplification of ErbB2 by Fluorescence in situ hybridization (FISH) Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) Adequate renal, hepatic and cardiac function Exclusion criteria: Prior chemotherapy, immunotherapy, biologic therapy or anti-ErbB1/ErbB2 therapy other than adjuvant therapy. [Prior neo-adjuvant or adjuvant therapy (including trastuzumab) will be allowed provided it was stopped at least 12 months before study entry. Patients with active brain metastases Patients with bilateral breast cancer, bone metastases as the only disease site or metastases to more than 30% of the hepatic parenchyma.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Lapatinib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC) | OR is defined as the number of participants achieving either a confirmed CR or PR, per Response Evaluation Criteria in Solid Tumors (RECIST, v 1.0). Best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of >= 1 new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made >=28 days after the original response. Participants with an unknown or missing response are treated as non-responders. | From the date of the first dose of investigational product to the first documented evidence of a confirmed CR or PR (up to Study Week 103) | 
| Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Investigator | OR is defined as the number of participants achieving either a confirmed CR or PR, per Response Evaluation Criteria in Solid Tumors (RECIST, v 1.0). Best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of >= 1 new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made >=28 days after the original response. Participants with an unknown or missing response are treated as non-responders. | From the date of the first dose of investigational product to the first documented evidence of a confirmed CR or PR (up to Study Week 103) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Benefit (CR or PR or Stable Disease [SD] for at Least 24 Weeks), as Assessed by the IRC and Investigator | Clinical benefit is defined as the numer of participants achieving either a confirmed CR (disappearance of all target lesions (TLs) and non-TLs) or PR (at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD,or complete resolution of TLs and the persistence of one or more non-TLs)or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [at least a 20% increase in the sum of the LD of target lesions, taking as a reference, the smallest sum LD recorded since the treatment started or the appearance of 1 or more new TLs or non-TLs and/or unequivocal progressionn of existing non-target lesions], taking as reference, the smallest sum LD since the treatment started) for at least 24 weeks. This was based on confirmed responses from the investigator assessment of clinical benefit. | From the date of the first dose of investigational product until the date of disease progression or death due to breast cancer (up to Study Week 103) | 
| Time to Response, as Assessed by the IRC and Investigator | Time to response is defined as the time from randomization until the first documented evidence of a PR or CR (whichever status is recorded first). Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the time to response taken as the first time the response was observed, not the confirmation assessment. Participants who withdraw with no tumor response were censored at the date of withdrawal from the study. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s). PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. | From the date of the first dose of investigational product until the first documented evidence of a PR or CR (up to Study Week 103) | 
| Duration of Response (DoR), as Assessed by the IRC and Investigator | DoR is defined for the subset of par. who had a confirmed CR (disappearance of all target lesions (TLs) and non-TLs) or PR (at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of >= 1 non-TL[s]) as the time from the first documented evidence of a CR or PR until the first documentation of radiological PD or death due to breast cancer, if sooner. PD is defined as >=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of >= 1 new lesions or unequivocal progression of existing non-TLs. For par. who did not progress or die, DoR was censored on the date of the last radiological scan. If a par.had only a Baseline visit or did not have a date of a radiological scan that was later than the date of initiation of anti-cancer therapy, DoR was censored at the start date of treatment. | From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Study Week 103) | 
| Progression-free Survival, as Assessed by the IRC and Investigator | Progression-free survival is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. Disease progression was based on the IRC's and investigator's assessments of the objective evidence (e.g., radiological scans and medical photographs). For participants who did not progress, or die, progression-free survival was censored at the time of the last IRC assessed radiological scan. | From the date of the first dose of investigational product until the earlier of the date of disease progression or death due to any cause (up to Study Week 103) | 
| Time to Treatment Failure, as Assessed by IRC and Investigator | 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 due any cause. For participants who did not progress, die or discontinue early, time to treatment failure was censored at the last scan date. | From randomization until the first documented sign of disease progression, death due to any cause, or early discontinuation from investigational product (up to Study Week 103) | 
| Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations. Refer to the general AE/SAE module for a list of non-serious AEs and SAEs. | From the date of the first dose of investigational product until 30 days after the last dose of investigational product (up to study week 192) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lapatinib, advanced, metastatic breast cancer, GW572016, ErbB2