A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer
Gemcitabine is considered one of the standard drugs for advanced pancreatic cancer and is approved by the FDA to treat it. Cabozantinib is a new drug that has demonstrated effectiveness against pancreatic cancer in laboratory experiments, especially when given with gemcitabine. Initial studies with cabozantinib in pancreatic cancer have shown some activity against the disease. The purpose of this study is to determine the safest and highest dose of cabozantinib that can be given together with standard doses of gemcitabine in patients with pancreatic cancer. This study will determine the safety and tolerability of this two drug combination.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer|
- Maximum tolerated dose [ Time Frame: 5 weeks ] [ Designated as safety issue: Yes ]The MTD is defined at the highest dose level at which ≤25% of patients experience a dose-limiting toxicity (DLT).
- Progression-free survival (PFS) [ Time Frame: day-7 of cycle 1 until PD or death ] [ Designated as safety issue: Yes ]Progression-free survival (PFS, a secondary endpoint) will be calculated from day-7 of cycle 1 of study treatment, until documented disease progression or death
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||January 2019|
|Estimated Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Experimental: cabozantinib with gemcitabine
The Study Treatment Period will consist of continued treatment during which time patients will receive cabozantinib and gemcitabine until either disease progression or the occurrence of unacceptable drug-related toxicity
Daily oral cabozantinib administered days -7 until disease progression, intolerable adverse event(s) or patient choice.
Other Name: XL184Drug: gemcitabine
Gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.
Other Name: Gemzar
Preclinical work at the University of Michigan has demonstrated that inhibition of c-Met with cabozantinib prevented the development of metastatic disease in an intra-cardiac injection model in NOD/SCID mice. Additionally, the combination of cabozantinib and gemcitabine demonstrated improved tumor control compared to either agent alone in a relevant orthotopic implantation mouse model.
Combining gemcitabine with the c-Met inhibitor cabozantinib in advanced pancreatic cancer is a novel strategy that takes advantage of an established cytotoxic agent with one that targets a pathway known to be important for the growth, dissemination, and resistance of this disease.
|Contact: Cancer AnswerLinefirstname.lastname@example.org|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Mark Zalupski 734-615-3969 email@example.com|
|Principal Investigator:||Mark Zalupski, MD||University of Michigan Cancer Center|