Vismodegib and Gemcitabine Hydrochloride in Treating Patients With Advanced Pancreatic Cancer
|Recurrent Pancreatic Carcinoma Stage IV Pancreatic Cancer||Drug: Gemcitabine Hydrochloride Other: Laboratory Biomarker Analysis Drug: Vismodegib||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Cancer Stem Cells and Inhibition of Hedgehog Pathway Signaling in Advanced Pancreas Cancer: A Pilot Study of GDC-0449 in Combination With Gemcitabine|
- Percent Decrease From Baseline in CD44+/ CD24+/ ESA+ Cells From Needle Biopsy Calculated Using FACS [ Time Frame: 3 weeks ]Proportion of CD44+CD24+ESA+ cells from needle biopsy were calculated at baseline and at 3 weeks using FACS. The difference between the two time points was calculated.
- The Number of Participants With an Objective Best Response (CR + PR) [ Time Frame: Up to 4 weeks ]The number of participants with either a complete response (CR) or a partial response (PR) will be calculated. A CR is defined as the disappearance of all target lesions. A PR is defined as at least a 30% decrease in the sum of the diameters of target lesions.
- Progression Free Survival [ Time Frame: 3 months ]Assessed using the Kaplan-Meier method. The 95% confidence interval for this estimate will be computed using the Greenwood's formula.
- Proportion of Treated Patients Experiencing Grade 3+ Toxicity Per National Cancer Institute Common Toxicity Criteria (CTC) Version 3.0 [ Time Frame: Up to 4 weeks ]Will be reported along with exact binomial 95% confidence intervals. Specific toxicities of all grades will be tabulated and reported.
|Study Start Date:||June 2010|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (vismodegib, gemcitabine hydrochloride)
Patients receive vismodegib PO QD on days 1-28 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 (beginning in course 2). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Gemcitabine Hydrochloride
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Vismodegib
I. To obtain tumor biopsies before and after therapy with GDC-0449 (vismodegib) to evaluate the effect of inhibition of hedgehog signaling on pancreatic cancer stem cells by: evaluating the tumor for number and percentage of pancreatic cancer stem cells before and after treatment with GDC-0449.
I. To assess progression free survival (PFS) at 3 months following treatment with GDC-0449 and gemcitabine (gemcitabine hydrochloride).
II. To assess response rate to treatment and overall survival in patients with advanced pancreas cancer treated with GDC-0449 alone and in combination with gemcitabine.
III. To evaluate the toxicity of GDC-0449 alone and in combination with gemcitabine.
Patients receive vismodegib orally (PO) once daily (QD) on days 1-28 and gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15 (beginning in course 2). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01195415
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Mark Zalupski||University of Michigan Cancer Center|