Conditions: Neoplasms, Breast
Keywords: trastuzumab ErbB2 paclitaxel Herceptin Taxol ErbB1 metastatic breast cancer Stage IV breast cancer lapatinib
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 63
Healthy volunteers: no

Brief summary:
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.

Detailed description:
The primary objective of this study was to evaluate and compare time to progression (TTP). The Primary objective for open label phase was to determine the safety and tolerability of lapatinib when administered in combination with both paclitaxel and trastuzumab. The study first enrolled an open label safety cohort of 20 patients to assess the tolerability of the triplet combination. This was a 1 arm, 3 cohort study stage.

Open-label Phase: Patients were sequentially enrolled into three cohorts and received an open-label combination of paclitaxel, trastuzumab and lapatinib: Cohort 1 received paclitaxel 80mg/m2 IV weekly for 3 weeks of a 4 week cycle, trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly, and lapatinib 1000 mg PO daily. Cohort 2 received paclitaxel 70mg/m2 IV weekly for 3 weeks of a 4 week cycle, trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly, and lapatinib 1000 mg PO daily. Cohort 3 paclitaxel 80mg/m2 IV weekly for 3 weeks of a 4 week cycle, trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly, and lapatinib 750 mg PO daily.

Randomized Phase: was terminated following the poor recruitment rate in the open-label safety stage. No subjects were enrolled into the randomization stage.

In summary, at approximately 3.5 years the primary analysis which included demographics, efficacy and safety were conducted; at approximately 7 years protocol amendment 7 cancelled collection of efficacy endpoints, and only key safety endpoints were to be collected; the final analysis was performed at approximately 14 years.

Arms:
arm 1: Participants received: paclitaxel 80mg/m2 IV weekly for 3 weeks of a 4 week cycle plus trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly plus lapatinib 1000 mg PO daily arm 2: Participants received paclitaxel 70mg/m2 IV weekly for 3 weeks of a 4 week cycle plus trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly plus lapatinib 1000 mg PO daily. arm 3: Participants in this arm received 80mg/m2 IV weekly for 3 weeks of a 4 week cycle plus trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly plus lapatinib 750 mg PO

Interventions: intervention 1: lapatinib intervention 2: paclitaxel intervention 3: trastuzumab
Intervention descriptions: intervention 1: (GW572016) 1000 mg QD intervention 2: 80 mg/m2 IV weekly for three weeks intervention 3: 4 mg/kg loading dose and 2 mg/kg weekly IV

Protocol document: