Lapatinib In Chemotherapy-Naive Or Metastatic Breast Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms, Breast
• Intervention / Treatment: Drug: Lapatinib

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 2

Contacts and Locations

Study Locations

• Chile
  • Región Metro De Santiago
    • Santiago, Región Metro De Santiago, Chile, 8380456
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 7500921
      • GSK Investigational Site
• Hong Kong
  • Pokfulam, Hong Kong
    • GSK Investigational Site
• India
  • Delhi, India, 110085
    • GSK Investigational Site
  • Hyderabad, Andhra Pradesh, India, 500482
    • GSK Investigational Site
  • Pune, India, 411001
    • GSK Investigational Site
• Malaysia
  • Bandar Tun Razak, Cheras, Malaysia, 59100
    • GSK Investigational Site
  • Kubang Kerian, Malaysia, 16150
    • GSK Investigational Site
  • Tanjong Bungah, Malaysia, 10450
    • GSK Investigational Site
  • Tanjong Bungah, Malaysia, 11200
    • GSK Investigational Site
• Mexico
  • Mexico, Mexico
    • GSK Investigational Site
  • Oaxaca
    • Ixtaltepec / Espinal, Oaxaca, Mexico, 70140
      • GSK Investigational Site
  • Yucatán
    • Merida, Yucatán, Mexico, 97500
      • GSK Investigational Site
• Pakistan
  • Karachi, Pakistan
    • GSK Investigational Site
  • Karachi, Pakistan, 74800
    • GSK Investigational Site
  • Karachi, Pakistan, 54000
    • GSK Investigational Site
  • Lahore, Pakistan
    • GSK Investigational Site
  • Rawalpindi, Pakistan
    • GSK Investigational Site
• Peru
  • Callao, Peru, Callao 2
    • GSK Investigational Site
  • Lima, Peru, Lima 11
    • GSK Investigational Site
  • Lima, Peru, Lima 34
    • GSK Investigational Site
  • Lima, Peru, Lima 13
    • GSK Investigational Site
• Poland
  • Bydogoszcz, Poland, 85-796
    • GSK Investigational Site
  • Krakow, Poland, 31-115
    • GSK Investigational Site
  • Olsztyn, Poland, 10-228
    • GSK Investigational Site
• Singapore
  • Singapore, Singapore, 258500
    • GSK Investigational Site
  • Singapore, Singapore, 169610
    • GSK Investigational Site
• Taiwan
  • Taipei, Taiwan, 100
    • GSK Investigational Site
  • Taipei, Taiwan, 114
    • GSK Investigational Site
• United States
  • Florida
    • Hollywood, Florida, United States, 33021
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Lipton A, Leitzel K, Ali SM, Carney W, Platek G, Steplewski K, Westlund R, Gagnon R, Martin AM, Maltzman J. Human epidermal growth factor receptor 2 (HER2) extracellular domain levels are associated with progression-free survival in patients with HER2-positive metastatic breast cancer receiving lapatinib monotherapy. Cancer. 2011 Nov 1;117(21):5013-20. doi: 10.1002/cncr.26101. Epub 2011 Mar 31.

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: August 18, 2004
• First Submitted That Met QC Criteria: August 20, 2004
• First Posted (Estimate): August 23, 2004

Study Record Updates

• Last Update Posted (Actual): February 28, 2017
• Last Update Submitted That Met QC Criteria: January 16, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: lapatinib; advanced; metastatic breast cancer; GW572016; ErbB2
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lapatinib
• Other Study ID Numbers: EGF20009