NCT01700010

Trial of Lapatinib and Weekly Paclitaxel for Advanced Urothelial Cancer

Phase II Trial of Lapatinib and Weekly Paclitaxel for Advanced Platinum Refractory Urothelial Cancer

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Michigan Rogel Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will involve subjects who have advanced urothelial cancer who are platinum refractory (platinum based chemotherapies that are not effective in treating the cancer), and who are over-expressing EGFR and/or HER2, or do not over-express EGFR and HER2. Genetic expression is a process that takes inherited information in genes (like DNA sequence), and from that information makes a specific functional product (sometimes called a gene product) such as RNA (ribonucleic acid) or protein. Normal tissue cells have a particular genetic expression, which changes when they turn into cancer. EGFR and HER2 are involved in the process by which normal cells are transformed into cancer cells. The main purpose of the study is to look at the proportion of subjects, who over-express EGFR and/or HER2, who do not progress (cancer gets worse) after 16 weeks of study treatment with daily lapatinib and weekly paclitaxel. The study will also look at the safety and effectiveness of this therapy in all subjects. Another part of this study will look at blood and tissue samples. Blood samples will be collected to see how many cells express EGFR and HER2 before study treatment and at the time the cancer gets worse. Tumor tissue will be analyzed to look at the expression of certain genes in advanced urothelial cancer. Some gene expression tests can reveal how cancer cells are different from normal cells and the results might lead to more accurate diagnosis and treatment.

Detailed description

Bladder cancer caused 14,680 deaths in 2010 in the US. In advanced bladder cancer, MVAC (methotrexate, vinblastine, adriamycin and cisplatin) and GC (gemcitabine, cisplatin) combination chemotherapy demonstrate comparable efficacy with response rates of 45%- 50%. Despite the reasonable initial response to platinum based chemotherapy, median time to progression on first line therapy is only 7 months and median survival approximately 15 months. There is no standard second line therapy after platinum based chemotherapy in the US and no survival benefit has been noted with any agent. Median progression free survival (PFS) is around 2 months in platinum refractory urothelial cancer (PRUC) and overall survival (OS) is 6 - 8 months with single agent second line therapy. Combination chemotherapy does not prolong overall survival. Given the dire prognosis in PRUC and the lack of efficacy of conventional chemotherapy, preclinical investigations and clinical research have focused on identification of novel molecular targets. Lapatnib is approved by the FDA for the treatment of breast cancer. Paclitaxel is approved by the FDA for the treatment of sarcoma, breast and lung cancers. Lapatinib and paclitaxel are not approved for advanced urothelial cancer; however, the FDA allows the use of these drugs in this study for research purposes.

Conditions

• Urothelial Cancer
• Bladder Cancer

Interventions

Type	Name	Description
DRUG	Lapatinib and Paclitaxel	Lapatinib comes in tablet form and is taken by mouth at a dose of 1,000 mg every day. Paclitaxel will be given through the vein (IV) at a dose of 80 mg/m2 on days 1, 8, and 15 at each 28 day cycle. If cancer does not progress and study treatment can be tolerated after 6 cycles of paclitaxel and lapatinib, paclitaxel will be stopped and lapatinib will continue until disease progression, side effects cannot be tolerated, participant is removed from or withdraws from study, or for other reasons. Subjects with locally advanced disease who respond to treatment and are felt to be appropriate for local therapy may proceed to receive local therapy as deemed appropriate by the managing physician after a minimum of 6 cycles or upon achieving complete remission followed by an additional 2 cycles. Subjects who proceed to receive local therapy will be removed from protocol therapy. Subjects who elect not to receive or are not candidates for local therapy may continue treatment on protocol.

Timeline

• Start date: 2012-11-01
• Primary completion: 2017-01-01
• Completion: 2019-01-01
• First posted: 2012-10-04
• Last updated: 2013-01-17

Locations

1 site across 1 country: United States