A Phase I/Expansion Study of Dasatinib (Gem/Dsat)
The purpose of this study is to find the highest dose of the drugs gemcitabine and dasatinib that can be given for the treatment of pancreatic cancer. Gemcitabine (also called Gemzar™)is a drug that is given intravenously. Dasatinib (also called Sprycel™) is a tablet and will be taken by mouth.
Gemcitabine is approved by the Food and Drug Administration (FDA) for the treatment of advanced breast, lung and pancreatic cancer. Dasatinib is approved by the FDA for the treatment of chronic myeloid leukemia (CML), acute lymphoblastic leukemia or for patients that are resistant to imatinib mesylate (Gleevec™ ).
This study will try to find the highest doses of these drugs that can be tolerated when taken in combination. The study will also look at how the drugs work in the body, and will see if there is any effect on pancreatic cancer.
Refractory Solid Tumors
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- 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 [ Time Frame: Phase I portion of the study ] [ Designated as safety issue: Yes ]
- To describe any dose limiting toxicities for these regimens [ Time Frame: Every 28 days or as clinically indicated ] [ Designated as safety issue: Yes ]
- To describe and non-dose limiting toxicities for these regimens [ Time Frame: Every 28 days or as clinically indicated ] [ Designated as safety issue: Yes ]
- To preliminarily describe markers of efficacy for gemcitabine plus dasatinib in patients with previously untreated metastatic pancreatic cancer: response rate, progression free survival, overall survival. [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
- To preliminarily describe changes in blood and urine based biomarkers,at baseline compared to first restaging and at progression, for patients with previously untreated metastatic pancreatic cancer treated on the expanded cohorts at the MTD/RPTD. [ Time Frame: baseline, first restaging, progression ] [ Designated as safety issue: No ]
|Study Start Date:||April 2007|
|Study Completion Date:||May 2012|
|Primary Completion Date:||June 2010 (Final data collection date for primary outcome measure)|
|Active Comparator: A||
1000mg/m2, Days 1, 8, 15
Other Name: GemzarDrug: dasatinib
50mg, PO, QD
Other Name: Sprycel
|Active Comparator: B||
1000mg/m2, days 1, 8, 15
Other Name: GemzarDrug: dasatinib
50mg, PO, BID
Other Name: Sprycel
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 Center
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00598091
|United States, North Carolina|
|UNC Lineberger, Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Wake Forest Baptist Medical Center|
|Winston-Salem, North Carolina, United States|
|Principal Investigator:||Hope C Uronis, MD||Duke University|