Lapatinib, Cisplatin, Gemcitabine as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Urothelial Cancer

Phase 1

Completed

• Conditions: Transitional Cell Cancer of the Renal Pelvis and Ureter; Bladder Cancer

• Registration Number: NCT00623064
• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

* 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.

Secondary

* 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.

Study Timeline

• Study Start: 2007-11
• Study First Submitted: 2008-02-22
• Study First Submitted QC: 2008-02-22
• Study First Posted: 2008-02-25
• Primary Completion: 2012-06
• Study Completion: 2012-08
• Status Verified: 2014-06
• Last Update Submitted: 2014-06-30
• Last Update Posted: 2014-07-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method
Antitumor activity according to RECIST
Pharmacokinetic profile of lapatinib ditosylate in combination with cisplatin/gemcitabine hydrochloride and cisplatin/gemcitabine hydrochloride

Trial Locations

Locations (1)

Rigshospitalet - Copenhagen University Hospital; 🇩🇰 Copenhagen, Denmark