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Lapatinib In Chemotherapy-Naive Or Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00089999
First received: August 18, 2004
Last updated: September 11, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Neoplasms, Breast
Drug: Lapatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Investigator [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Time to Response, as Assessed by the IRC and Investigator [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Duration of Response (DoR), as Assessed by the IRC and Investigator [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Progression-free Survival, as Assessed by the IRC and Investigator [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Time to Treatment Failure, as Assessed by IRC and Investigator [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 138
Study Start Date: June 2004
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Lapatinib
    Other Name: Lapatinib
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00089999

  Show 31 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00089999     History of Changes
Other Study ID Numbers: EGF20009
Study First Received: August 18, 2004
Results First Received: August 18, 2014
Last Updated: September 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
lapatinib
advanced
metastatic breast cancer
GW572016
ErbB2

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Lapatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014