Phase I Study Evaluating the Combination of Lapatinib + Vinorelbine in Patients With Locally Advanced or Metastatic Breast Cancer Overexpressing HER2
- Evaluate the tolerability and feasibility of the lapatinib ditosylate and vinorelbine
ditartrate combination by determining the maximum tolerated dose of vinorelbine
ditartrate in combination with a biologically active dose of lapatinib ditosylate.
- Determine the maximum administered dose.
- Investigate the pharmacokinetic interactions related to the combination of vinorelbine
ditartrate and lapatinib ditosylate.
- Determine the toxicity of vinorelbine ditartrate and lapatinib ditosylate.
- Determine the objective response rate in patients with measurable lesions.
- Validate the safety and efficacy of the oral vinorelbine ditartrate and lapatinib
ditosylate combination, according to the vinorelbine ditartrate oral/IV dose
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive oral lapatinib ditosylate on days -7 to 21 for course 1 and on days 1-21
for all other courses. Patients also receive vinorelbine ditartrate IV over 15 minutes on
days 1 and 8. Courses repeat every 21 days for up to 12 months in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-9 patients receive escalating doses of lapatinib ditosylate and vinorelbine
ditartrate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the
dose preceding that at which 2 of 9 patients experience dose-limiting toxicity during course
Once the MTD is determined for oral lapatinib ditosylate and IV vinorelbine ditartrate, an
additional cohort of 9 patients receive oral vinorelbine ditartrate with oral lapatinib
ditosylate as above.
Primary Purpose: Treatment
Toxicity as assessed by NCI CTCAE v3.0
Pierre Fumoleau, MD, PhD
Centre de Lutte Contre le Cancer Georges-Francois Leclerc