Phase I Study of Cisplatin, Gemcitabine and Lapatinib as First Line Treatment in Advanced/Metastatic Urothelial Cancer
- Determine the maximum tolerated dose and recommended doses of lapatinib ditosylate when
administered with gemcitabine hydrochloride and cisplatin, and determine on the basis
of acute dose-limiting toxicity in course 1 in patients with locally advanced or
metastatic transitional cell carcinoma of the urothelial tract.
- To determine any relationship between drug exposure and adverse events in these
- To assess the antitumor activity in these patients.
OUTLINE: This is a multicenter, dose-escalation study of lapatinib ditosylate.
- Lapatinib ditosylate, cisplatin, and gemcitabine hydrochloride: Patients receive oral
lapatinib ditosylate once daily on days 1-28, cisplatin IV on day 2, and gemcitabine
hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 4 weeks in
the absence of disease progression or unacceptable toxicity until the recommended dose
of lapatinib ditosylate is determined.
- Lapatinib ditosylate, cisplatin, gemcitabine hydrochloride: Subsequently enrolled
patients receive oral lapatinib ditosylate (beginning at one dose level below the
recommended dose determined in the previous combination) once daily on days 1-21,
cisplatin IV on day 1, gemcitabine hydrochloride IV over 30 minutes. Courses repeat
every 3 weeks in the absence of disease progression or unacceptable toxicity.
All patients undergo blood sample collection periodically for pharmacokinetic analysis.
After completion of study treatment, patients are followed weekly.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of lapatinib ditosylate in combination with cisplatin/gemcitabine hydrochloride and cisplatin/gemcitabine hydrochloride based on the documentation of the acute dose-limiting toxicity in course 1
Gedske Daugaard, MD, DMSc
European Union: European Medicines Agency