NCT00320411

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

Completed Phase 2 Results posted Last updated 31 January 2019

What this trial tests

Phase 2 trial testing lapatinib in Neoplasms, Breast in 62 participants. Completed in 1 April 2009.

Timeline

28 November 2005

Primary endpoint
1 April 2009

1 April 2009

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	62
Start date	28 November 2005
Primary completion	1 April 2009
Estimated completion	1 April 2009
Sites	9 locations across Japan

Drugs / interventions tested

• lapatinib (LAPATINIB) — full drug profile →

Conditions studied

• Neoplasms, Breast — all drugs for Neoplasms, Breast →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 20 to 74, female only, with Neoplasms, Breast. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Tumor Response Primary · 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.

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.

Complete response

Group	Value	95% CI
Lapatinib Monotherapy	1

Partial response

Group	Value	95% CI
Lapatinib Monotherapy	8

Stable disease

Group	Value	95% CI
Lapatinib Monotherapy	18

Progressive disease

Group	Value	95% CI
Lapatinib Monotherapy	29

Unknown

Group	Value	95% CI
Lapatinib Monotherapy	2

Duration of Response Secondary · 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.

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.

Group	Value	95% CI
Lapatinib Monotherapy	20.6	16.1 – 32.1

Time to Progression Secondary · 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.

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.

Group	Value	95% CI
Lapatinib Monotherapy	8.4	7.4 – 23.9

Clinical Benefit Secondary · 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.

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

Group	Value	95% CI
Lapatinib Monotherapy	17.2

Time to Response Secondary · 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.

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).

Group	Value	95% CI
Lapatinib Monotherapy	111	56 – 279

4-month Progression Free Survival Secondary · Baseline to Month 4 (Week 16)

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

Group	Value	95% CI
Lapatinib Monotherapy	32.3

6-month Progression Free Survival Secondary · Baseline to Month 6 (Week 24)

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

Group	Value	95% CI
Lapatinib Monotherapy	22.8

Overall Survival Secondary · 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.

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

Group	Value	95% CI
Lapatinib Monotherapy	43.1	24.3 – 80.7

Mean Phosphorylated 58 kDa Serine/Threonine Protein Kinase (p-AKT) H Score for All Participants Secondary · Tumor samples taken at baseline

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.

Group	Value	95% CI
Lapatinib Monotherapy	13.9	± 26.32

Mean p-BAD H Score for All Participants Secondary · Tumor samples taken at baseline

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.

Group	Value	95% CI
Lapatinib Monotherapy	12.8	± 36.50

Mean Bcl-2 H Score for All Participants Secondary · Tumor samples taken at baseline

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.

Group	Value	95% CI
Lapatinib Monotherapy	20.9	± 47.82

Mean Epidermal Growth Factor Receptor 3 (ErbB3) H Score for All Participants Secondary · Tumor samples taken at baseline

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.

Group	Value	95% CI
Lapatinib Monotherapy	185.5	± 50.61

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lapatinib Monotherapy

Serious: 14/58 (24%)

Deaths: —

Serious adverse events (17 terms)

Reaction	System	Lapatinib Monotherapy
Anorexia	Metabolism and nutrition disorders	—
Pneumonia	Infections and infestations	—
Hepatic function abnormal	Hepatobiliary disorders	—
Hypercalcemia	Metabolism and nutrition disorders	—
Cellulitis	Infections and infestations	—
Hepatomegaly	Hepatobiliary disorders	—
Malaise	General disorders	—
Disease progression	General disorders	—
Lymphocyte count decreased	Investigations	—
Blood uric acid increased	Investigations	—
Nausea	Gastrointestinal disorders	—
Diarrhea	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Back pain	Musculoskeletal and connective tissue disorders	—
Ventricular dysfunction	Cardiac disorders	—
Dizziness	Nervous system disorders	—
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—

Other adverse events (182 terms — click to expand)

Reaction	System	Lapatinib Monotherapy
Diarrhea	Gastrointestinal disorders	—
Stomatitis	Gastrointestinal disorders	—
Rash	Skin and subcutaneous tissue disorders	—
Fatigue	General disorders	—
Nausea	Gastrointestinal disorders	—
Anorexia	Metabolism and nutrition disorders	—
Weight decreased	Investigations	—
Pruritus	Skin and subcutaneous tissue disorders	—
Nasopharyngitis	Infections and infestations	—
Alanine aminotransferase increased	Investigations	—
Vomiting	Gastrointestinal disorders	—
Acne	Skin and subcutaneous tissue disorders	—
Aspartate aminotransferase increased	Investigations	—
Constipation	Gastrointestinal disorders	—
Pyrexia	General disorders	—
Insomnia	Psychiatric disorders	—
Back pain	Musculoskeletal and connective tissue disorders	—
Dry skin	Skin and subcutaneous tissue disorders	—
Blood alkaline phosphatase increased	Investigations	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	—
Blood bilirubin increased	Investigations	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—
Headache	Nervous system disorders	—
Abdominal pain upper	Gastrointestinal disorders	—
Exfoliative rash	Skin and subcutaneous tissue disorders	—
Comedone	Skin and subcutaneous tissue disorders	—
Chest pain	General disorders	—
Nasal dryness	Respiratory, thoracic and mediastinal disorders	—
Abdominal pain	Gastrointestinal disorders	—
Seborrhoeic dermatitis	Skin and subcutaneous tissue disorders	—
Nail disorder	Skin and subcutaneous tissue disorders	—
Ingrowing nail	Skin and subcutaneous tissue disorders	—
Paronychia	Infections and infestations	—
Malaise	General disorders	—
Hemoglobin decreased	Investigations	—
Neutrophil count decreased	Investigations	—
Blood urine present	Investigations	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Dysgeusia	Nervous system disorders	—

Most-reported serious reactions: Anorexia, Pneumonia, Hepatic function abnormal, Hypercalcemia, Cellulitis, Hepatomegaly, Malaise, Disease progression.

Data from ClinicalTrials.gov NCT00320411 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.