Gemcitabine and Pazopanib in Chemotherapy Naïve Patients With Advanced/Metastatic Urothelial Carcinoma Ineligible for Cisplatin-based Chemotherapy
Gemcitabine and Cisplatin are standard chemotherapy drugs used to treat advanced urothelial cancer. There is no standard chemotherapy for patients who cannot receive Cisplatin. However, most patients are treated with the chemotherapy drugs Gemcitabine and Carboplatin.
In this study, the researchers hope to learn what effects, good and/or bad, the combination of Gemcitabine and Pazopanib has on urothelial cancer. Gemcitabine is given intravenously (through the veins) and works by killing rapidly dividing cells in the body, including cancer cells. Pazopanib is an oral chemotherapy and works by decreasing the blood supply to tumors which limits the tumor's source of oxygen and nutrients.
The combination of Gemcitabine and Pazopanib is being tested in research studies such as this one. As of August 2011, more than 18 patients with various types of cancer have received treatment with Gemcitabine and Pazopanib. The main goal of this clinical research study is to learn if the study drugs Gemcitabine and Pazopanib can shrink or slow the growth of urothelial cancer. The safety of this drug will also be studied. The physical state, changes in the size of the tumor, and laboratory findings will help us decide if the combination of Gemcitabine and Pazopanib is safe and effective.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Gemcitabine and Pazopanib in Chemotherapy Naïve Patients With Advanced/Metastatic Urothelial Carcinoma Ineligible for Cisplatin-based Chemotherapy|
- progression free survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]Progression Free Survival will be calculated from the start of treatment until progressive disease or death. Patients who die before documented progression will be considered failures at their time of death. If the patient did not progress or die, the patient will be censored on the date of last follow-up. Response and progression will be evaluated in this study using the international criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Safety and tolerability will be assessed according to the NIH/NCI CTCAE v4.0,.
- response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]as defined by partial and complete response using RECIST for the combination of gemcitabine and pazopanib in treatment naïve patients with advanced/metastatic UC who are ineligible to receive cisplatin-based chemotherapy. Response rate defined as the percentage of partial and complete response, and will be estimated using binomial proportions.
- overall survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]Overall survival duration is defined as the time from start of treatment until death and will be analyzed using the Kaplan Meier method. Patients still alive at the time of analysis will be censored on the date of last follow-up.
- Correlative studies [ Time Frame: 2 years ] [ Designated as safety issue: No ]We will evaluate expression levels of NF-κB, phospho-Akt, and jagged-1 in pre-treatment specimens by immunohistochemistry (IHC). The expression levels by immunohistochemistry will be categorized in 3 groups as: no expression (IHC Score 0), low expression (IHC Score 1+), and high expression (IHC Score 2+ and 3+) and will be correlated with PFS using a log rank test and with response to treatment (complete response/partial response versus no response) using Fisher's exact test.
|Study Start Date:||June 2012|
|Estimated Study Completion Date:||June 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Experimental: Gemcitabine and Pazopanib
This is a phase II trial of gemcitabine and pazopanib in previously untreated patients with advanced/metastatic urothelial carcinoma (UC) who are ineligible for cisplatin-based chemotherapy.
Drug: Gemcitabine and Pazopanib
Patients will receive gemcitabine 1200 mg/m2 intravenously on day 1 and day 8 and pazopanib 800 mg orally daily day 1 through day 21 (1 cycle = 21 days). Patients will receive 6 cycles of combination therapy (gemcitabine and pazopanib) unless disease progression or unacceptable toxicity occurs. Patients that achieve stable disease, a partial response, or a complete response after completion of 6 cycles, and who are not candidates for consolidation surgery, will be eligible to continue pazopanib monotherapy at the same dose and schedule until disease progression for a maximum of 18 additional cycles.
|United States, New Jersey|
|Memoral Sloan Kettering Cancer Center|
|Basking Ridge, New Jersey, United States|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center @ Suffolk|
|Commack, New York, United States, 11725|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Memorial Sloan-Kettering Cancer Center at Mercy Medical Center|
|Rockville Centre, New York, United States, 11570|
|Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center|
|Sleepy Hollow, New York, United States, 10591|
|Principal Investigator:||Dean Bajorin, MD||Memorial Sloan-Kettering Cancer Center|