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CompletedNCT00320411Updated Jan 31, 2019Results posted

GW572016 In Patients With ErbB2 Over - Expressing Advanced Or Metastatic Breast Cancer

A Phase 2 interventional study of lapatinib in Neoplasms, Breast, sponsored by GlaxoSmithKline. Completed at 9 sites in Japan. Open to female participants aged 20 Years to 74 Years. Per ClinicalTrials.gov, last updated 2019-01-31.

Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
62
Allocation
Non-randomized
Ages
20 Years to 74 Years
Sex
Female
01

Study summary

This study (EGF104911) is designed to evaluate the efficacy and safety of lapatinib in patients with advanced or metastatic breast cancer. Eligible subjects must have ErbB2 overexpressing tumors and are refractory to treatment with anthracycline, taxanes and trastuzumab containing regimens. The study data obtained from EGF104911 will be combined with the data from EGF100642 and integrated analysis will be carried out in order to enhance the credibility of the study results.

02

Conditions studied

  • Neoplasms, Breast

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Keywords

  • Stage IV breast cancer
  • Herceptin
  • metastatic breast cancer
  • ErbB1
  • ErbB2
  • trastuzumab
  • lapatinib
03

In context

Breast Neoplasms

12,820 studies on the registry are indexed under Breast Neoplasms; 2,920 are open to participants now.

This study's enrollment of 62 is below the median of 72 across 9,494 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,647 studies on the registry; 118 are open to participants now.

Of its 264 completed or terminated interventional studies of FDA-regulated products, 239 (91%) have results posted.

Browse GlaxoSmithKline studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years to 74 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

A subject will be considered eligible for inclusion in this study only if all of the following criteria apply:

  • Life expectancy of ≥16 weeks from the start of lapatinib therapy;
  • Signed informed consent obtained from the patient;
  • Subjects must have histologically confirmed breast cancer with advanced (Stage IIIb, IIIc with T4 lesion) or metastatic disease (including recurrent patients);
  • Subjects must meet the following criteria regarding prior therapy:
  • Anthracyclines, taxanes:
  • If anthracycline- and taxane-containing regimens are administered sequentially;
  • Subjects should have been provided with at least 2 cycles each and at least 4 cycles in total.
  • If anthracycline- and taxane-containing regimen are administered concurrently;
  • Subjects should have been provided with at least 4 cycles in total. or
  • Subjects should have been provided with at least 2 cycles in total and provided progressive disease occurred.
  • If anthracycline- and taxane-containing regimen are administered separately;
  • Subjects should have been provided with at least 4 cycles each. or
  • Subjects should have been provided with at least 2 cycles each and provided progressive disease occurred each regimen.
  • Trastuzumab:
  • Prior treatment must contain trastuzumab alone or in combination with other chemotherapy for at least 6 weeks of standard doses.
  • Subjects must meet the following criteria regarding ErbB2 expression (defined by the following status before undergoing trastuzumab therapy.)

Patients with ErbB2 overexpression:

  • 3+ by IHC, or FISH+
  • 2+ by IHC and FISH+ are also eligible. However, patients with "2+ by IHC" who have previously been treated with trastuzumab should undergo FISH before study entry, if they have not had this test performed before, and are considered eligible only if their tumours are categorised as FISH+.
  • Documentation of tumor progression or relapse after the most recent treatment is required.
  • Archived tumor tissue must be available to compare tumor response with intra-tumoral expression levels of biomarkers (ErbB1 and ErbB2).
  • Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors); (See "6.3. Efficacy")
  • A female, ≥20 and ≤74 years (at the time of giving consent), is eligible to enter and participate in this study if she is of:
  • Non-childbearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are post-menopausal, i.e., at least 1 year has past since the last menstrual period); or is
  • The subject has a negative serum pregnancy test at screening, and agrees to one of the following from 2 weeks prior to administration of the first dose of lapatinib until 28 days after the final dose of lapatinib＊.
  • Complete abstinence from intercourse:
  • Consistent and correct use of one of the following acceptable methods of birth control:
  • Injectable progestogen;
  • Any intrauterine device (IUD);
  • Oral contraceptives (either combined or Progestogen only);
  • Barrier methods including diaphragm or condom with a spermicide.
  • At least 3 weeks since the last dose of prior last chemotherapy, immunotherapy, biologic therapy, hormonal therapy, or radiotherapy (except for local radiation therapy to pain relief) for cancer or since the date of completion of surgery (except for minor surgical procedures) before beginning treatment with lapatinib, except for trastuzumab which must be discontinued at least 2 weeks prior to beginning of study drug. Subjects must have recovered or stabilized sufficiently from side effects associated with prior therapy;
  • Prior to enrollment, radiation therapy is allowed to a limited field (e.g. painful bone mets, painful lumps), if it is not the sole site of measurable and/or assessable disease. Patients must have completed treatment and adequately recovered, in particular from bone marrow suppression.
  • Subjects who are not on bisphosphonate therapy. Bisphosphonates initiated prior to study medication are allowed; however, initiation of bisphosphonate following the first dose of study medication is not allowed. Prophylactic use of bisphosphonates is only permitted for treatment of osteoporosis.
  • Subjects with stable CNS metastasis (asymptomatic and off systemic steroids and anticonvulsants for at least 3 months) are also eligible;
  • ECOG Performance Status of 0 to 2;
  • Able to swallow and retain oral medication;
  • Left ventricular ejection fraction (LVEF), measured by echocardiogram (ECHO), above the institutional's lower limit of normal (LVEF of ≥50% in such case as normal range of LVEF is not provided by institution).
  • Subjects must have adequate organ function as defined below:
  • Myelofunction:

Neutrophil count ≥1500 /mm3 Hemoglobin ≥9 g/dL (at least 2 weeks after blood transfusion if needed) Platelet count ≥100,000 /mm3

  • Hepatic function:

Albumin ≤2.5 g/dL Total bilirubin ≤1.5xULN AST, ALT: ≤3xULN (without liver metastases), ≤5xULN (if documented liver metastases)

  • Renal function:

Serum creatinine ≤1.5 mg/dL, or creatinine clearance ≤40 mL/min (calculated by the Cockcroft and Gault Method)

  • Subjects who can visit the hospital once weekly (±3 days) at least in the first month after the start of lapatinib therapy and then every 4 weeks (±1 week) until the last assessment.

Exclusion criteria

Exclusion Criteria:

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

  • Pregnant or lactating females;
  • Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded;
  • History of other malignancy. Subjects who have been disease free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible;
  • Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety * [* ≥Grade 3 (according to NCI-CTCAE Version 3.0), as a general rule];
  • Active or uncontrolled infection;
  • Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure;
  • Known history of or clinical evidence of leptomeningeal carcinomatosis;
  • Participated in a clinical study within the past 28 days of the first dose of lapatinib;
  • Prior therapy with an ErbB1inhibitor (e.g., gefinitib) and/or ErbB2 inhibitor other than trastuzumab;
  • Has taken/received prohibited inhibitors (including foods) of CYP3A4 within 7 days prior to the first dose of study medication or has taken/received prohibited inducers inducers (including foods) of CYP3A4 within 14 days prior to the first dose of study medication(Refer to Appendix 7).
  • The subject has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients
  • Patients ineligible for participation in the study in the judgment of the investigator/sub investigator.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
62 participants (actual)

Study arms

  • Experimental
    Lapatinb

    Lapatinib 1500mg QD

    Drug: lapatinib

Interventions

06

What researchers measure

Primary outcomes

  1. Overall Tumor Response

    Tumor response was measured as the number of participants achieving either a complete response (CR; disappearance of all target lesions) or partial response (PR; 30% decrease in the sum of the longest diameter of target lesions) among all participants who received study treatment. Tumor response was evaluated as the best response in accordance with response evaluation criteria in solid tumors (RECIST). Progressive disease: a 20% increase in the sum of the longest diameter of target lesions. Stable disease: small changes that do not meet the above-mentioned criteria.

    Time frame: Baseline and then followed every 4 weeks until disease progression or death. If treatment was terminated due to adverse events, then followed every 12 weeks until disease progression is noted.

Secondary outcomes

  1. Duration of Response

    Duration of response is defined as the time between the point at which efficacy was noted until disease progression or death due to breast cancer.

    Time frame: First noted efficacy to disease progression; baseline and followed every 4 weeks until disease progression or death. If treatment was terminated due to adverse events, then followed every 12 weeks until disease progression is noted.

  2. Time to Progression

    Time to progression was defined as the time from the start of treatment until disease progression or death. Disease progression is defined as a 20% increase in the sum of the longest diameter of target lesions.

    Time frame: Baseline to disease progression or death; baseline and then followed every 4 weeks until disease progression or death. If treatment was terminated due to adverse events, then followed every 12 weeks until disease progression or death.

  3. Clinical Benefit

    Clinical benefit was defined as the percentage of participants achieving complete response, partial response, and stable disease for more than 24 weeks.

    Time frame: Time at which all participants had been followed for at least 24 weeks; baseline and then followed every 4 weeks until disease progression (DP) or death. If treatment was terminated due to adverse events, then followed every 12 weeks until DP or death.

  4. Time to Response

    Time to response was defined as the time from the start of treatment until first documented evidence of partial or complete tumor response (whichever status is recorded first).

    Time frame: Time at which all participants had been followed for at least 24 weeks; baseline and then followed every 4 weeks until disease progression (DP) or death. If treatment was terminated due to adverse event, then followed every 12 weeks until DP or death.

  5. 4-month Progression Free Survival

    The percentage of participants without progression or deaths at 4 months (16 weeks) after the start of dosing.

    Time frame: Baseline to Month 4 (Week 16)

  6. 6-month Progression Free Survival

    The percentage of participants without progression or deaths at 6 months (24 weeks) after the start of dosing.

    Time frame: Baseline to Month 6 (Week 24)

  7. Overall Survival

    Overall survival was measured as the time between the start of dosing until death, regardless of cause.

    Time frame: Start of dosing to death; baseline and then followed every 4 weeks until death while on treatment. If alive at time of treatment termination, then followed every 12 weeks until death.

  8. Mean Phosphorylated 58 kDa Serine/Threonine Protein Kinase (p-AKT) H Score for All Participants

    Intra-tumoral expression levels of AKT, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

    Time frame: Tumor samples taken at baseline

  9. Mean p-BAD H Score for All Participants

    Intra-tumoral expression levels of BAD, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

    Time frame: Tumor samples taken at baseline

  10. Mean Bcl-2 H Score for All Participants

    Intra-tumoral expression levels of Bcl-2, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

    Time frame: Tumor samples taken at baseline

  11. Mean Epidermal Growth Factor Receptor 3 (ErbB3) H Score for All Participants

    Intra-tumoral expression levels of ErbB3, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

    Time frame: Tumor samples taken at baseline

  12. Mean Epidermal Growth Factor Receptor 4 (ErbB4) H Score for All Participants

    Intra-tumoral expression levels of ErbB4, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

    Time frame: Tumor samples taken at baseline

  13. Mean Phosphorylated Extracellular Signal-regulated Kinase (p-ERK) H Score for All Participants

    Intra-tumoral expression levels of ERK, a tumor tissue biomarker, were measured.using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

    Time frame: Tumor samples taken at baseline

  14. Mean Heregulin H Score for All Participants

    Intra-tumoral expression levels of Heregulin, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

    Time frame: Tumor samples taken at baseline

  15. Mean Insulin-like Growth Factor 1 Receptor (IGF1R) H Score for All Participants

    Intra-tumoral expression levels of IGF1R, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

    Time frame: Tumor samples taken at baseline

  16. Mean Survivin H Score for All Participants

    Intra-tumoral expression levels of Survivin, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

    Time frame: Tumor samples taken at baseline

  17. Mean Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) H Score for All Participants

    Intra-tumoral expression levels of TUNEL, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

    Time frame: Tumor samples taken at baseline

07

Results

Posted Dec 14, 2009

Participant flow

Participant flow — Overall Study
MilestoneLapatinib Monotherapy
Started62
Completed58
Not completed4
Withdrew: No investigational product admin.4

Outcome measures

PrimaryOverall Tumor Response

Tumor response was measured as the number of participants achieving either a complete response (CR; disappearance of all target lesions) or partial response (PR; 30% decrease in the sum of the longest diameter of target lesions) among all participants who received study treatment. Tumor response was evaluated as the best response in accordance with response evaluation criteria in solid tumors (RECIST). Progressive disease: a 20% increase in the sum of the longest diameter of target lesions. Stable disease: small changes that do not meet the above-mentioned criteria.

Time frame:
Baseline and then followed every 4 weeks until disease progression or death. If treatment was terminated due to adverse events, then followed every 12 weeks until disease progression is noted.
Reported as:
Number · participants
Overall Tumor Response
participantsLapatinib Monotherapy
Complete response1
Partial response8
Stable disease18
Progressive disease29
Unknown2
SecondaryDuration of Response

Duration of response is defined as the time between the point at which efficacy was noted until disease progression or death due to breast cancer.

Time frame:
First noted efficacy to disease progression; baseline and followed every 4 weeks until disease progression or death. If treatment was terminated due to adverse events, then followed every 12 weeks until disease progression is noted.
Reported as:
Median · weeks
Duration of Response
weeksLapatinib Monotherapy
Duration of Response20.6 (16.1 to 32.1)
SecondaryTime to Progression

Time to progression was defined as the time from the start of treatment until disease progression or death. Disease progression is defined as a 20% increase in the sum of the longest diameter of target lesions.

Time frame:
Baseline to disease progression or death; baseline and then followed every 4 weeks until disease progression or death. If treatment was terminated due to adverse events, then followed every 12 weeks until disease progression or death.
Reported as:
Median · weeks
Time to Progression
weeksLapatinib Monotherapy
Time to Progression8.4 (7.4 to 23.9)
SecondaryClinical Benefit

Clinical benefit was defined as the percentage of participants achieving complete response, partial response, and stable disease for more than 24 weeks.

Time frame:
Time at which all participants had been followed for at least 24 weeks; baseline and then followed every 4 weeks until disease progression (DP) or death. If treatment was terminated due to adverse events, then followed every 12 weeks until DP or death.
Reported as:
Number · percentage of participants
Clinical Benefit
percentage of participantsLapatinib Monotherapy
Clinical Benefit17.2
Statistical analysis
  • Lapatinib Monotherapy · Percentage of participants: 17.2 · 95% CI 8.6 to 29.4
SecondaryTime to Response

Time to response was defined as the time from the start of treatment until first documented evidence of partial or complete tumor response (whichever status is recorded first).

Time frame:
Time at which all participants had been followed for at least 24 weeks; baseline and then followed every 4 weeks until disease progression (DP) or death. If treatment was terminated due to adverse event, then followed every 12 weeks until DP or death.
Reported as:
Median · Days
Time to Response
DaysLapatinib Monotherapy
Time to Response111 (56 to 279)
Secondary4-month Progression Free Survival

The percentage of participants without progression or deaths at 4 months (16 weeks) after the start of dosing.

Time frame:
Baseline to Month 4 (Week 16)
Reported as:
Number · percentage of participants
4-month Progression Free Survival
percentage of participantsLapatinib Monotherapy
4-month Progression Free Survival32.3
Statistical analysis
  • Lapatinib Monotherapy · Percentage of participants: 32.3 · 95% CI 20.0 to 44.7
Secondary6-month Progression Free Survival

The percentage of participants without progression or deaths at 6 months (24 weeks) after the start of dosing.

Time frame:
Baseline to Month 6 (Week 24)
Reported as:
Number · percentage of participants
6-month Progression Free Survival
percentage of participantsLapatinib Monotherapy
6-month Progression Free Survival22.8
Statistical analysis
  • Lapatinib Monotherapy · Percentage of participants: 22.8 · 95% CI 11.6 to 34.0
SecondaryOverall Survival

Overall survival was measured as the time between the start of dosing until death, regardless of cause.

Time frame:
Start of dosing to death; baseline and then followed every 4 weeks until death while on treatment. If alive at time of treatment termination, then followed every 12 weeks until death.
Reported as:
Median · weeks
Overall Survival
weeksLapatinib Monotherapy
Overall Survival43.1 (24.3 to 80.7)
SecondaryMean Phosphorylated 58 kDa Serine/Threonine Protein Kinase (p-AKT) H Score for All Participants

Intra-tumoral expression levels of AKT, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

Time frame:
Tumor samples taken at baseline
Reported as:
Mean · units on a scale
Mean Phosphorylated 58 kDa Serine/Threonine Protein Kinase (p-AKT) H Score for All Participants
units on a scaleLapatinib Monotherapy
Mean Phosphorylated 58 kDa Serine/Threonine Protein Kinase (p-AKT) H Score for All Participants13.9 ± 26.32
SecondaryMean p-BAD H Score for All Participants

Intra-tumoral expression levels of BAD, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

Time frame:
Tumor samples taken at baseline
Reported as:
Mean · units on a scale
Mean p-BAD H Score for All Participants
units on a scaleLapatinib Monotherapy
Mean p-BAD H Score for All Participants12.8 ± 36.50
SecondaryMean Bcl-2 H Score for All Participants

Intra-tumoral expression levels of Bcl-2, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

Time frame:
Tumor samples taken at baseline
Reported as:
Mean · units on a scale
Mean Bcl-2 H Score for All Participants
units on a scaleLapatinib Monotherapy
Mean Bcl-2 H Score for All Participants20.9 ± 47.82
SecondaryMean Epidermal Growth Factor Receptor 3 (ErbB3) H Score for All Participants

Intra-tumoral expression levels of ErbB3, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

Time frame:
Tumor samples taken at baseline
Reported as:
Mean · units on a scale
Mean Epidermal Growth Factor Receptor 3 (ErbB3) H Score for All Participants
units on a scaleLapatinib Monotherapy
Mean Epidermal Growth Factor Receptor 3 (ErbB3) H Score for All Participants185.5 ± 50.61
SecondaryMean Epidermal Growth Factor Receptor 4 (ErbB4) H Score for All Participants

Intra-tumoral expression levels of ErbB4, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

Time frame:
Tumor samples taken at baseline
Reported as:
Mean · units on a scale
Mean Epidermal Growth Factor Receptor 4 (ErbB4) H Score for All Participants
units on a scaleLapatinib Monotherapy
Mean Epidermal Growth Factor Receptor 4 (ErbB4) H Score for All Participants133.3 ± 60.47
SecondaryMean Phosphorylated Extracellular Signal-regulated Kinase (p-ERK) H Score for All Participants

Intra-tumoral expression levels of ERK, a tumor tissue biomarker, were measured.using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

Time frame:
Tumor samples taken at baseline
Reported as:
Mean · units on a scale
Mean Phosphorylated Extracellular Signal-regulated Kinase (p-ERK) H Score for All Participants
units on a scaleLapatinib Monotherapy
Mean Phosphorylated Extracellular Signal-regulated Kinase (p-ERK) H Score for All Participants12.2 ± 17.30
SecondaryMean Heregulin H Score for All Participants

Intra-tumoral expression levels of Heregulin, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

Time frame:
Tumor samples taken at baseline
Reported as:
Mean · units on a scale
Mean Heregulin H Score for All Participants
units on a scaleLapatinib Monotherapy
Mean Heregulin H Score for All Participants55.3 ± 42.37
SecondaryMean Insulin-like Growth Factor 1 Receptor (IGF1R) H Score for All Participants

Intra-tumoral expression levels of IGF1R, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

Time frame:
Tumor samples taken at baseline
Reported as:
Mean · units on a scale
Mean Insulin-like Growth Factor 1 Receptor (IGF1R) H Score for All Participants
units on a scaleLapatinib Monotherapy
Mean Insulin-like Growth Factor 1 Receptor (IGF1R) H Score for All Participants153.5 ± 48.44
SecondaryMean Survivin H Score for All Participants

Intra-tumoral expression levels of Survivin, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

Time frame:
Tumor samples taken at baseline
Reported as:
Mean · units on a scale
Mean Survivin H Score for All Participants
units on a scaleLapatinib Monotherapy
Mean Survivin H Score for All Participants79.0 ± 47.25
SecondaryMean Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) H Score for All Participants

Intra-tumoral expression levels of TUNEL, a tumor tissue biomarker, were measured using immunohistochemistry methods that incorporated both intensity and distribution of staining. A value designated the H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+: 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum score of 0 to a maximum score of 300; the maximum score indicates the strongest expression.

Time frame:
Tumor samples taken at baseline
Reported as:
Mean · units on a scale
Mean Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) H Score for All Participants
units on a scaleLapatinib Monotherapy
Mean Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) H Score for All Participants48.9 ± 26.88

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Lapatinib Monotherapy—14/58 (24.1%)58/58 (100%)
Most frequent serious events
Showing 10 of 17
Most frequent serious events
EventLapatinib Monotherapy
AnorexiaMetabolism and nutrition disorders3/58
PneumoniaInfections and infestations2/58
Hepatic function abnormalHepatobiliary disorders2/58
HypercalcemiaMetabolism and nutrition disorders1/58
CellulitisInfections and infestations1/58
HepatomegalyHepatobiliary disorders1/58
MalaiseGeneral disorders1/58
Disease progressionGeneral disorders1/58
Lymphocyte count decreasedInvestigations1/58
Blood uric acid increasedInvestigations1/58
Most frequent other events
Showing 10 of 182
Most frequent other events
EventLapatinib Monotherapy
DiarrheaGastrointestinal disorders36/58
StomatitisGastrointestinal disorders27/58
RashSkin and subcutaneous tissue disorders23/58
FatigueGeneral disorders23/58
NauseaGastrointestinal disorders22/58
AnorexiaMetabolism and nutrition disorders20/58
Weight decreasedInvestigations14/58
PruritusSkin and subcutaneous tissue disorders13/58
NasopharyngitisInfections and infestations13/58
Alanine aminotransferase increasedInvestigations13/58

Baseline characteristics

Age, Continuous
Age, Continuous(years)Lapatinib Monotherapy
Mean54.6 ± 8.52
Sex: Female, Male
Sex: Female, Male(Participants)Lapatinib Monotherapy
Female58
Male0
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Lapatinib Monotherapy
Asian58
08

Study locations

9 sites
  • GSK Investigational Site
    Ehime, 791-0280, Japan
  • GSK Investigational Site
    Fukuoka, 814-0180, Japan
  • GSK Investigational Site
    Kanagawa, 241-0815, Japan
  • GSK Investigational Site
    Okayama, 701-0192, Japan
  • GSK Investigational Site
    Tochigi, 329-0498, Japan
  • GSK Investigational Site
    Tokyo, 104-0045, Japan
  • GSK Investigational Site
    Tokyo, 113-8677, Japan
  • GSK Investigational Site
    Tokyo, 135-8550, Japan
  • GSK Investigational Site
09

References and documents

Publications

  • Toi M, Iwata H, Fujiwara Y, Ito Y, Nakamura S, Tokuda Y, Taguchi T, Rai Y, Aogi K, Arai T, Watanabe J, Wakamatsu T, Katsura K, Ellis CE, Gagnon RC, Allen KE, Sasaki Y, Takashima S. Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast cancer: efficacy, safety, and biomarker results from Japanese patients phase II studies. Br J Cancer. 2009 Nov 17;101(10):1676-82. doi: 10.1038/sj.bjc.6605343. Epub 2009 Oct 20. PubMed 19844234 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 31, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00320411
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
May 3, 2006
Start date
Nov 28, 2005
Primary completion
Apr 1, 2009
Completion
Apr 1, 2009
Results posted
Dec 14, 2009
Last update
Jan 31, 2019

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline
View the source record on ClinicalTrials.gov ↗

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