Lapatinib, Cisplatin, Gemcitabine as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Urothelial Cancer
RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib together with combination chemotherapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib when given together with cisplatin and gemcitabine as first-line therapy in treating patients with locally advanced or metastatic urothelial cancer.
Transitional Cell Cancer of the Renal Pelvis and Ureter
Drug: gemcitabine hydrochloride
Drug: lapatinib ditosylate
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Cisplatin, Gemcitabine and Lapatinib as First Line Treatment in Advanced/Metastatic Urothelial Cancer|
- 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 [ Designated as safety issue: Yes ]
- Pharmacokinetic profile of lapatinib ditosylate in combination with cisplatin/gemcitabine hydrochloride and cisplatin/gemcitabine hydrochloride [ Designated as safety issue: No ]
- Antitumor activity according to RECIST [ Designated as safety issue: No ]
|Study Start Date:||November 2007|
|Estimated Study Completion Date:||August 2012|
|Estimated Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
- 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 patients.
- 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.
|Rigshospitalet - Copenhagen University Hospital|
|Copenhagen, Denmark, 2100|
|Study Chair:||Gedske Daugaard, MD, DMSc||Rigshospitalet, Denmark|