A Phase I Study of the Combination of Gemcitabine Plus Dasatinib in Patients With Refractory Solid Tumors With an Expanded Cohort in Advanced Pancreatic Cancer
This open-label, multicenter, non-randomized phase I trial of gemcitabine plus once and
twice daily dasatinib is designed to assess the safety, tolerability, maximum tolerated
dose/recommended phase II dose, and preliminary efficacy of this combination in adult
patients with advanced solid tumors and with previously untreated metastatic pancreatic
cancer. Patients will be accrued at Duke University Medical Center, the Duke Oncology
Network, the University of North Carolina at Chapel Hill and Wake Forest Baptist Medical
Patients will be accrued to either of the gemcitabine/dasatinib arms in alternating
sequential order. In the case where there is an open slot on a particular arm but not the
alternative, the enrolled patient will be assigned to that open slot. For example, at the
start of the trial, patient #1 will be treated on the gemcitabine with dasatinib twice daily
dosing arm, patient #2 on the gemcitabine with dasatinib once daily dosing arm, patient #3
on the gemcitabine with dasatinib twice daily dosing arm, and so on. However, if, due to
cohort expansion there is a slot available on one treatment arm but not the other, the
patient will be accrued to the open slot.
Additionally, if one arm is held, delayed, or not pursued, accrual to the alternate arm may
continue. Patients and their treating physicians will not be able to choose on their own
which treatment arm that patient will be assigned to. This enrollment procedure will be the
procedure for the entire trial.
For the dose escalation portion of the trial, patients will only be accrued at Duke
University Medical Center. For the expanded cohort portion of patients with previously
untreated metastatic pancreatic cancer treated at the recommended phase II dose of each arm,
patients may be accrued at Duke University Medical Center,and the sites listed above.
NOTE: The first stage closed as of December 2008. Subjects will only be enrolled into the
second stage of the this study.
- Toxicity will be assessed every visit, and as clinically indicated.
- Dose limiting toxicities will be assessed during cycle 1.
- Efficacy will be assessed every 2 cycles, and as clinically indicated.
- Plasma biomarkers will be assessed at baseline and at every restaging.
- Tissue based biomarkers (tumor and granulation tissue) will be assessed in up to 15
patients treated at Duke only. Tissue biopsy sets (a 4mm "stimulus" biopsy and a 5mm
"granulation" tissue biopsy, both in the same location) will also be done both
pre-treatment and on-treatment. Pre-treatment biopsies will be done on days -7 and 1,
respectively. On-treatment biopsies will be done on days 1 and 8, respectively.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the MTD/Recommended Phase II Dose (RPTD) of gemcitabine plus dasatinib once daily and twice daily dosing in patients with advanced solid tumors
Phase I portion of the study
Hope C Uronis, MD
United States: Food and Drug Administration
|Duke University Medical Center||Durham, North Carolina 27710|
|UNC Lineberger, Comprehensive Cancer Center||Chapel Hill, North Carolina 27599|
|Wake Forest Baptist Medical Center||Winston-Salem, North Carolina|