Phase I study of Cisplatin, gemcitabin (+ paclitaxel) and lapatinib as first line treatment in advanced/metastatic urothelial cancer

Completed

Conditions: 10038364
urothelial cancer

Registration Number: NL-OMON31194

Lead Sponsor: European Organisation for Research in Treatment of Cancer (EORTC)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

- Histologically proven TCC of the urothelial tract in patients who overexpress HER1 and/or HER2 (IHC 2/3+ FISH/CISH +)
- Metastatic or locally advanced disease with involvement of at least one target not in previously irradiated fields
- Tissue from the primary or metastatic site must be available for biomarker status determination
- Measurable disease according to RECIST
- Normal bone marrow, renal, hepatic and cardiac functions

Exclusion Criteria

- No prior chemotherapy for metastatic disease.
- No radiotherapy within the last 4 weeks before inclusion
- Drugs which are inducers or inhibitors of CYP3A4 are prohibited

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To identify the maximum tolerated dose (MTD) of Lapatinib in combination with<br /><br>cisplatin/gemcitabine and cisplatin/gemcitabine/paclitaxel based on the<br /><br>documentation of the acute dose limiting toxicity (DLT) in cycle 1.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- To determine the pharmacokinetic profile of Lapatinib in combination with<br /><br>cisplatin/gemcitabine and cisplatin/gemcitabine/paclitaxel<br /><br><br /><br>- To assess the anti-tumor activity according to RECIST, in those patients with<br /><br>measurable disease<br /><br><br /><br>- To explore the patient population by determination of intra-tumoral<br /><br>expression levels of relevant biomarkers from tumor tissue: three Erb/EGFR<br /><br>family members (HER1, HER2,HER3, HER4), AKT (58kDa serine/threonine protein<br /><br>kinase), TUNEL, p53 , MAPK and Insulin-like growth factor-1 (IGF-1R) and<br /><br>potentially other signalling pathways likeVEGF together with biomarkers that<br /><br>are downstream of these receptors.</p><br>