Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Urologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Trastuzumab

Carboplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Antineoplastic Agents, Immunological

Herceptin - 4mg/kg day 1 of cycle 1; 2mg/kg day 8 and 15 of cycle 1 and subsequent cycles.

Paclitaxel - 200mg/m\^2 on day 1 Carboplatin - AUC 5 on day 1 Gemcitabine - 800 mg/m\^2 on day 1 and 8

Maha Hussain, MD

Purpose: The purpose of this study is to evaluate the efficacy and safety of treatment with trastuzumab (Herceptin) along with the three other chemotherapy drugs, paclitaxel, carboplatin and gemcitabine, in patients who have advanced urothelial cancer. This clinical trial will also collect information (alternative therapy, response rates, overall survival) from enrolled patients with HER2 negative tumors who are ineligible to receive study treatment.

Trastuzumab (Herceptin), Paclitaxel, Carboplatin and Gemcitabine in Advanced Urothelial Cancer

Phase II Evaluation of Trastuzumab (Herceptin), Paclitaxel, Carboplatin, and Gemcitabine in the Treatment of Advanced Urothelial Cancer

The primary objective of the study is to evaluate the toxicity profile of combination of herceptin, paclitaxel, carboplatin and gemcitabine in patients with locally recurrent or metastatic urothelial carcinoma who overexpress HER2.

Genentech, Inc.

University of Michigan Rogel Cancer Center

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

TKI258

Novartis Pharmaceuticals

This study will evaluate the efficacy of TKI258 in patients with advanced urothelial cancer

Phase II Study of TKI258 in Advanced Urothelial Carcinoma

A Phase II Multi-center, Non-randomized, Open Label Study of TKI258 in FGFR3 Mutated and FGFR3 Wild Type Advanced Urothelial Carcinoma

Urinary Bladder Neoplasms

Urinary Bladder Diseases

Vinblastine

Patients will receive vinflunine standard regimen (intravenous infusion every three weeks) as specified per drug label plus additional pazopanib as daily oral medication. Doses of pazopanib will be escalated in 200 mg/d steps during phase I up to a maximum of 800 mg/d.

In Phase II the patients will be given pazopanib + vinflunine at maximum tolerated dose.

Pazopanib as add-on to vinflunine

Urothelial carcinoma of the bladder mostly is chemically induced and represents the second prevalent urooncological disease. About 20% of newly diagnosed urothelial carcinoma cases of the bladder are already advanced or metastasized. Before 2008 2009 no second line therapy after failure of primary systemic therapy of advanced / metastatic disease was established outside of clinical trials. The actual standard for this situation was a supportive, symptomatic therapy. Vinflunine has demonstrated improved survival from 4.3 to 6.9 months (p=0.04), with an adequate disease control, good symptom control and with acceptable toxicity. Based on these results, this compound became standard se¬cond line treatment for refractory metastatic bladder cancer disease after failure of platinum-containing therapy. As the prognosis still remains poor, new treatment opportunities have to be explored.

The target-specific therapy with Pazopanib suggests a positive influence of both inductive and perioperative treatment of solid tumors. Pazopanib has been approved by the FDA and the EMA for the treatment of advance renal cell carcinoma. Results for advanced urothelial carcinoma are missing so far as well as data on tolerability of the combination of both vinflunine and pazopanib. As the pharmacodynamic properties as well as the safety profile of both drugs are different, assumption is justified that there might occur additive efficacy effects without addition of adverse outcomes. Aim of the study thus is

1. To define the maximum tolerated dose (MTD) of Pazopanib in combination with Vinflunine in a phase-I-setting and
2. To further assess efficacy and safety of the combination at the MTD level in phase II.

During the pase-I-part of the study different doses of pazopanib will be added to the standard vinflunine scheme in groups of 6 patients maximum. Dose escalation will only be performed in the next patient group if not more than one out of six patients shows dose-limiting toxicity. Each patient will be treated with the drug combination for a duration of two vinflunine cycles, that is six weeks.

During the phase-II study new patients will be treated with the drug combination at maximum-tolerated dose until disease progression (assessed by RECIST 1.1 procedures).

Pazopanib and Vinflunine in Urothelial Cancer of the Bladder

Target-specific Therapy With Pazopanib as Add-on to Vinflunine in Patients With Advanced or Metastatic Urothelial Carcinoma of the Bladder After Failure of Platinum-based Treatment

MTD ist defined as the dose level with dose-limiting toxicity occurring in maximum one out of six patients.

Progression-free survival will be assessed by means of RECIST 1.1. methodology

Prof. Dr. Thomas Otto

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trastuzumab (Herceptin), Paclitaxel, Carboplatin and Gemcitabine in Advanced Urothelial Cancer	NCT00151034	Urologic Neopla...	Trastuzumab Paclitaxel Carboplatin Gemcitabine	18 Years -	University of Michigan Rogel Cancer Center
Phase II Study of TKI258 in Advanced Urothelial Carcinoma	NCT00790426	Urothelial Canc...	TKI258	18 Years -	Novartis
Pazopanib and Vinflunine in Urothelial Cancer of the Bladder	NCT01265940	Advanced Urothe...	Pazopanib as ad...	18 Years -	Lukas-Krankenhaus GmbH
Trastuzumab (Herceptin), Paclitaxel, Carboplatin and Gemcitabine in Advanced Urothelial Cancer	NCT00151034	Urologic Neopla...	Trastuzumab Paclitaxel Carboplatin Gemcitabine	18 Years -	University of Michigan Rogel Cancer Center
Pazopanib and Vinflunine in Urothelial Cancer of the Bladder	NCT01265940	Advanced Urothe...	Pazopanib as ad...	18 Years -	Lukas-Krankenhaus GmbH

Spots Global Cancer Trial Database for advanced urothelial cancer