Last reviewed · How we verify

NCT00272987

ErbB2 Over-expressing Metastatic Breast Cancer Study Using Paclitaxel, Trastuzumab, and Lapatinib

Terminated Phase 3 Results posted Last updated 28 April 2023
What this trial tests

Phase 3 trial testing lapatinib in Neoplasms, Breast in 63 participants. Terminated before completion.

Timeline
13 December 2005
Primary endpoint
31 July 2009
21 October 2019

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment63
Start date13 December 2005
Primary completion31 July 2009
Estimated completion21 October 2019
Sites16 locations across Belgium, United States

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, 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.

Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Mean/Standard Deviation Primary · From the date of the first dose of the investigational product to end of study, up to approx. 14 years

Extent of exposure is defined as the duration of the treatment administered during the study. The mean duration of exposure to lapatinib, trastuzumab and paclitaxel is calculated as the number of weeks between the start and end of treatment.

Lapatinib
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg70.9± 115.44
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg93.1± 147.92
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg82.5± 135.79
Trastuzumab
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg60.7± 72.07
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg72.2± 88.66
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg62.3± 75.52
Paclitaxel
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg26.9± 16.88
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg29.4± 23.00
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg23.8± 14.87
Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Median/Min-Max Primary · From the date of the first dose of the investigational product to end of study, up to approx. 14 years

Extent of exposure is defined as the duration of the treatment administered during the study. The mean duration of exposure to lapatinib, trastuzumab and paclitaxel is calculated as the number of weeks between the start and end of treatment.

Lapatinib
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg33.03 – 615
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg38.52 – 547
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg32.51 – 574
Trastuzumab
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg33.02 – 343
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg37.02 – 271
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg31.51 – 245
Paclitaxel
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg22.02 – 86
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg23.52 – 94
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg22.01 – 63
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Primary · From the date of the first dose of investigational product until 30 days after the last dose of investigational product, up to approx. 14 years

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 li

Any AEs
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg29
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg14
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg20
Any SAEs
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg14
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg6
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg5
Number of Participants Who Died Due to Any Cause Primary · From the date of the first dose of investigational product until last patient last visit, up to approximately 14 years

Number of participants who died due to any cause throughout the study including off-treatment deaths (on-treatment deaths are reported for the All-Cause Mortality in the AE section).

GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg12
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg2
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg1
Number of Events of Diarrhea With the Indicated Characteristics Primary · From the date of the first dose of investigational product until 30 days after the last dose of investigational product, up to approx. 3.5 years

Events of diarrhea are characterized as serious, related to investigational product, leading to withdrawal from the study and fatal. Participants could have been counted in more than one category.

Any Event
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg358
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg90
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg37
Serious
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg4
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Related to investigational product
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg347
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg75
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg26
Leading to withdrawal from study
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg2
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg1
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg1
Fatal
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Number of Events of Rash With the Indicated Characteristics Primary · From the date of the first dose of investigational product until 30 days after the last dose of investigational product, up to approx. 3.5 years

Events of rash are characterized as serious, related to investigational product, leading to withdrawal from the study and fatal. Participants could have been counted in more than one category.

Any Event
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg69
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg23
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg20
Serious
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg2
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Related to investigational product
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg55
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg12
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg7
Leading to withdrawal from study
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg3
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Fatal
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters Primary · Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years

Blood samples for clinical laboratory evaluation were taken at Baseline prior to the administration of investigational product and thereafter at each scheduled visit. Haematology parameters included haemoglobin, total white blood cell count (WBC), neutrophils, lymphocytes and platelets. Hematology data was summarized by the National Cancer Institute's Common toxicity criteria for adverse events (NCI CTCAE) toxicity grade (Version 3.0). Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling; Grade 5, death.

Haemaglobin, Grade 1
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg19
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg11
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg11
Haemaglobin, Grade 2
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg7
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg1
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg6
Haemaglobin, Grade 3
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg2
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg1
Haemaglobin, Grade 4
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg1
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Platelets, Grade 1
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg3
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Platelets, Grade 2
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg1
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Platelets, Grade 3
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Platelets, Grade 4
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg1
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters Primary · Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years

Blood samples for clinical laboratory evaluation were taken at Baseline prior to the administration of investigational product and thereafter at each scheduled visit. Clinical chemistry parameters included values \> upper limit of normal (ULN)=Hyper; values \< lower limit of normal (LLN)=Hypo of sodium (Hypernatraemia and Hyponatraemia), potassium (Hyperkalaemia and Hypokalaemia), calcium (Hypercalcaemia and Hypocalcaemia), glucose (Hyperglycaemia and Hyperglycaemia), creatinine (if \>2 milligram per deciliter \[mg/dL\]), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline p

Hypernatraemia, Grade 1
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg1
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg1
Hypernatraemia, Grade 2
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg1
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Hypernatraemia, Grade 3
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Hypernatraemia, Grade 4
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Hyponatraemia, Grade 1
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg8
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg1
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg1
Hyponatraemia, Grade 2
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Hyponatraemia, Grade 3
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg1
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Hyponatraemia, Grade 4
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Number of Events of Hepatotoxicity With the Indicated Characteristics Primary · From the date of the first dose of investigational product until 30 days after the last dose of investigational product, up to approx. 3.5 years

Events of hepatotoxicity are characterized as serious, related to investigational product, leading to withdrawal from the study and fatal. Participants could have been counted in more than one category.

Any Event
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg6
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg2
Serious
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Related to investigational product
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg5
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Leading to withdrawal from study
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Fatal
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0
Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points Primary · Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years

Blood pressure measurement included systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Baseline and every 4 weeks thereafter up to withdrawal/study completion and at the 30 day follow-up visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

SBP, Week 4
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0.5± 16.29
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-7.2± 20.70
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg-3.9± 22.76
SBP, Week 8
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg4.6± 12.35
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-8.6± 22.25
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg-2.7± 24.73
SBP, Week 12
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg3.2± 18.46
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-6.9± 17.09
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg-9.3± 23.54
SBP, Week 16
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0.8± 18.10
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-6.6± 15.26
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg-7.9± 24.43
SBP, Week 20
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg1.7± 17.80
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-11.5± 14.69
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg-13.8± 25.15
SBP, Week 24
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg2.9± 13.87
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-1.8± 11.81
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg-7.8± 26.06
SBP, Week 28
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg2.3± 19.10
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-5.7± 20.38
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg-5.2± 10.71
SBP, Week 32
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg3.2± 23.11
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-16.4± 10.03
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg-6.3± 5.51
Change From Baseline in Heart Rate at the Indicated Time Points Primary · Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years

Heart rate was measured at Baseline and every 4 weeks thereafter up to withdrawal/study completion and at the 30 day follow-up visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Week 4
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-1.714± 10.9099
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-3.417± 26.3593
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg3.333± 12.1268
Week 8
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-5.667± 14.7908
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-3.231± 16.8481
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg5.353± 10.7642
Week 12
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.217± 10.7109
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.417± 15.6812
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg-2.875± 10.6074
Week 16
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.478± 13.4667
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg2.625± 15.1369
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg-1.917± 10.9084
Week 24
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.476± 16.7768
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-5.300± 15.1808
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg5.167± 10.2843
Week 28
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-4.313± 16.0155
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-1.429± 17.7281
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg3.600± 8.5615
Week 32
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-4.933± 16.6496
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.500± 11.1098
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0.333± 10.5987
Week 36
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-5.000± 13.0128
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg4.857± 18.4791
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg7.000± 11.5326
Change From Baseline in Body Temperature at the Indicated Time Points Primary · Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years

Body temperature was measured at Baseline and every 4 weeks thereafter up to withdrawal/study completion and at the 30 day follow-up visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Week 4
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.229± 0.5062
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.242± 0.3605
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0.078± 0.5976
Week 8
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0.011± 0.5250
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.154± 0.4294
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0.247± 0.4652
Week 12
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0.021± 0.4374
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.567± 0.4960
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0.173± 0.4636
Week 16
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.052± 0.5814
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.127± 0.4880
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0.121± 0.5494
Week 20
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0.018± 0.5712
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.238± 0.4138
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0.300± 0.3536
Week 24
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg0.157± 0.5006
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.100± 0.4138
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0.017± 0.5193
Week 28
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.094± 0.4956
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.529± 0.4751
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0.300± 0.3536
Week 32
GroupValue95% CI
Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.156± 0.6077
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg-0.237± 0.2134
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg0.000± 0.2000

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) and Serious adverse events (SAEs) were collected from the first dose of investigational product to 30 days after the last dose of investigational product, up to approx.12 years (maximum exposure to Lapatinib (615 weeks) plus 30 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: Paclitaxel 80mg/Trastuzumab 4 mg/Lapatinib 1000mg
Serious: 14/29 (48%)
Deaths: 0/29
Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg
Serious: 6/14 (43%)
Deaths: 0/14
Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg
Serious: 5/20 (25%)
Deaths: 0/20

Serious adverse events (34 terms)

ReactionSystemCohort 1: Paclitaxel 80mg/…Cohort 2: Paclitaxel 70 mg…Cohort 3: Paclitaxel 80 mg…
DehydrationMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
Left ventricular dysfunctionCardiac disorders
DiarrhoeaGastrointestinal disorders
CellulitisInfections and infestations
Ejection fraction decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
ThrombocytopeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
Mucosal inflammationGeneral disorders
PyrexiaGeneral disorders
CholelithiasisHepatobiliary disorders
Drug hypersensitivityImmune system disorders
Cellulitis streptococcalInfections and infestations
Clostridium difficile colitisInfections and infestations
Infectious colitisInfections and infestations
PneumoniaInfections and infestations
Compression fractureInjury, poisoning and procedural complications
Rib fractureInjury, poisoning and procedural complications
Spinal compression fractureInjury, poisoning and procedural complications
HypocalcaemiaMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
Other adverse events (163 terms — click to expand)

ReactionSystemCohort 1: Paclitaxel 80mg/…Cohort 2: Paclitaxel 70 mg…Cohort 3: Paclitaxel 80 mg…
DiarrhoeaGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
AlopeciaSkin and subcutaneous tissue disorders
FatigueGeneral disorders
VomitingGastrointestinal disorders
NauseaGastrointestinal disorders
HypokalaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
MyalgiaMusculoskeletal and connective tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
StomatitisGastrointestinal disorders
Mucosal inflammationGeneral disorders
Upper respiratory tract infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
HeadacheNervous system disorders
ConstipationGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Weight decreasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
ParaesthesiaNervous system disorders
InsomniaPsychiatric disorders
Nail disorderSkin and subcutaneous tissue disorders
PyrexiaGeneral disorders
Ejection fraction decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Neuropathy peripheralNervous system disorders
Peripheral sensory neuropathyNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
LeukopeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Oedema peripheralGeneral disorders
Localised infectionInfections and infestations
Urinary tract infectionInfections and infestations
HypocalcaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Dehydration, Neutropenia, Left ventricular dysfunction, Diarrhoea, Cellulitis, Ejection fraction decreased, Hypokalaemia, Thrombocytopenia.

Data from ClinicalTrials.gov NCT00272987 adverse events section.

Sponsor's own description

This study was originally designed as a Phase III randomized, double blind, placebo controlled study to assess the safety and tolerability, and efficacy of paclitaxel plus trastuzumab plus lapatinib compared with paclitaxel plus trastuzumab plus placebo in women with ErbB2 overexpressing metastatic breast cancer. The planned study was a two stage design with an initial open-label safety stage to be conducted in approximately 65 subjects followed by a randomized phase conducted in a further 700 subjects. The open-label part of the study sequentially enrolled three cohorts with patients receiving a different dose combination of paclitaxel, trastuzumab and lapatinib. Following poor recruitment rate in the open label stage, the randomized stage of the study was terminated, thus no subjects were enrolled into the randomization stage.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Challenges in the Treatment of Triple Negative and HER2-Overexpressing Breast Cancer.
    Hoeferlin LA, E Chalfant C, Park MA. · · 2013 · cited 24× · PMID 24818173
  2. Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer.
    Hurvitz SA, Kakkar R. · · 2012 · cited 18× · PMID 24367193 · DOI 10.2147/bctt.s29996
  3. An open-label safety study of lapatinib plus trastuzumab plus paclitaxel in first-line HER2-positive metastatic breast cancer.
    Esteva FJ, Franco SX, Hagan MK, Brewster AM, et al · · 2013 · cited 15× · PMID 23697602 · DOI 10.1634/theoncologist.2012-0129

Verify or expand the search:

Other trials of lapatinib

Trials testing the same drug.

Other recruiting trials for Neoplasms, Breast

Currently open trials in the same condition.

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00272987.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing