NCT01138046

Phase I/II Study of Lapatinib in Combination With Paclitaxel as 1L Chemotherapy for ErbB2-positive MBC

An Open-label, Single-arm, Phase I/II Study of Lapatinib in Combination With Weekly Paclitaxel as First-line Chemotherapy for ErbB2-overexpressing Metastatic Breast Cancer Patients

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, non-randomized, multi-center study of lapatinib plus paclitaxel to evaluate safety, tolerability and efficacy in Japanese patients with ErbB2 over expressing advanced or metastatic breast cancer. Lapatinib 1500mg/day will be administered in combination with paclitaxel 80mg/m2/week. Lapatinib and paclitaxel will be administered until disease progression or withdrawal from the study due to unacceptable toxicity. The study will proceed in two phases. The first phase (Phase I part) will lead to evaluate safety and tolerability of lapatinib taken together with paclitaxel in the first 6 subjects. Pharmacokinetic profile also will be evaluated as the secondary objects. Then the study will move to the next treatment phase (Phase II part) to evaluate further safety and clinical activity, if no major safety concerns are raised during Phase I part. The primary objective of the study is to evaluate overall survival (OS), and the secondary objectives are Objective tumour response rate (ORR), Duration of response, Time to response, Clinical benefit and Progression-free survival (PFS) in 12 subjects.

Detailed description

This is an open-label, single-arm, Phase I/II study to evaluate the efficacy, safety and tolerability of weekly paclitaxel and lapatinib in subjects with ErbB2-overexpressing advanced or metastatic breast cancer who have not received prior therapy for metastatic disease. These subjects will receive weekly paclitaxel (80 mg/m2 IV for 3 weeks in a 4 week cycle) plus lapatinib (1500 mg once daily). Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. Subjects will be treated with paclitaxel for standard of 6 cycles, and may be continued at the discretion of investigators. If the subject experiences progression, an unacceptable toxicity related to paclitaxel, or termination of lapatinib therapy, paclitaxel therapy must be terminated any time of study period, even before 6 cycles of paclitaxel are given. This study consists of the Phase I and Phase II parts: Phase I part Tolerability and pharmacokinetics in 6 subjects will be evaluated in Phase I part of study and the tolerability criteria are set as follow: Tolerability criteria in first cycle; Concerning the safety tolerability of this trial, if 1 out of 6 first enrolled subjects meets the tolerability criteria, the study will proceed to phase II part and the regimen will judged as well tolerable. If 2 subjects meet the tolerability criteria, the sponsor will consult the safety review committee. GSK will finally judge based on the consultation regarding the tolerability and the medical significance. Grade 4 hematologic toxicities. Thrombocytopenia less than or equal to 25,000/mm3 Grade 3 or 4 and clinically significant non-haematologic toxicities. Inability to start cycle 2 within 2 weeks of scheduled dosing due to unresolved toxicity. For all 6 subjects enrolled, safety profiles occurred in cycle 1 are closely monitored individually. When considering the appropriateness of study continuation, not only the safety profiles noted in cycle 1 of this study, but also the safety profiles reported from pilot part of EGF104578 study and other relevant studies will be referred in order to make medical decisions. Phase II part After tolerability in 6 subjects enrolled in Phase I part is confirmed, further 6 subjects to be enrolled for Phase II part (i.e. total of 12 subjects). Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. All 12 subjects will be followed for survival.

Conditions

• Neoplasms, Breast

Interventions

Type	Name	Description
DRUG	Lapatinib in combination with weekly paclitaxel	These subjects will receive weekly paclitaxel (80 mg/m2 IV for 3 weeks in a 4 week cycle) plus lapatinib (1500 mg once daily, starting on the second day of phase I). Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. Study completion is defined as deaths after administering study treatment for more than once. Subjects will be treated with paclitaxel for standard of 6 cycles, and may be continued at the discretion of investigators. If the subject experiences progression, an unacceptable toxicity related to paclitaxel, or termination of lapatinib therapy, paclitaxel therapy must be terminated any time of study period, even before 6 cycles of paclitaxel are given.

Timeline

• Start date: 2010-04-01
• Primary completion: 2014-01-01
• Completion: 2014-01-01
• First posted: 2010-06-07
• Last updated: 2014-10-07
• Results posted: 2014-09-19

Locations

10 sites across 1 country: Japan