Conditions: Neoplasms, Breast
Keywords: ErbB2 positive human epidermal growth factor receptor 2 positive (Her2+) metastatic breast cancer Fluorescence in situ hybridization (FISH) positive Stage IV
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 444
Healthy volunteers: no

Brief summary:
This was a randomized, double-blind, placebo-controlled, multicenter, Phase III study to evaluate and compare the efficacy and safety of Lapatinib + Paclitaxel versus Placebo + Paclitaxel in men and women with ErbB2 amplified metastatic (Stage IV) breast cancer who had not received prior therapy for metastatic disease.

Detailed description:
Subjects were randomized to receive either Lapatinib (1500 mg once daily) + Paclitaxel (80 mg/m2 IV weekly for 3 weeks every 4 weeks) or Placebo (once daily) + Paclitaxel (80 mg/m2 IV weekly for 3 weeks every 4 weeks).

Subjects who progressed while on study and were on the placebo+paclitaxel arm were permitted to enter an extension phase of open label monotherapy therapy with lapatinib or open label combination therapy with lapatinib+paclitaxel and followed for response, progression and survival.

Based on the positive results in the primary analysis, Protocol Amendment 02 (dated 09 May 2011) discontinued further entry into the lapatinib monotherapy extension phase, and ongoing subjects taking placebo were permitted to replace it with open label lapatinib therapy (with or without continued paclitaxel therapy).

Following the primary Overall Survival (OS) analysis and subsequent implementation of Protocol Amendment 03, subjects who were still receiving active treatment entered the Long-term follow-up (LTFU) phase of the study. Reporting requirements in the LTFU phase were limited to Adverse events of special interest (AESI), Serious adverse events (SAEs) and pregnancy, and the subjects continued to receive treatment until the occurrence of unacceptable toxicity or disease progression (as determined by the investigator) or permanent withdrawal from treatment for any reason. Subjects who were no longer receiving active treatment were withdrawn from the study.

Arms:
arm 1: Paclitaxel and Lapatinib (Blinded) arm 2: Paclitaxel and Placebo (Blinded) arm 3: Open Label - Monotherapy (Lapatinib) arm 4: Open Label - Combination Therapy (Lapatinib and Paclitaxel)

Interventions: intervention 1: Lapatinib (GW572016) oral tablets intervention 2: Paclitaxel infusion intervention 3: Placebo
Intervention descriptions: intervention 1: 1500 mg oral daily continuously intervention 2: Paclitaxel 80 mg/m2 every 3 weeks, 4th week rest for minimum 6 months intervention 3: Paclitaxel Matching Placebo

Protocol document: