This phase I/II trial studies the side effects and best dose of WEE1 inhibitor AZD1775 when given together with gemcitabine hydrochloride and radiation therapy in treating patients with pancreatic cancer that cannot be removed by surgery. WEE1 inhibitor AZD1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, stopping them from dividing, or stopping them from spreading. Radiation therapy uses high energy x rays to kill tumor cells. Giving WEE1 inhibitor AZD1775 together with gemcitabine hydrochloride and radiation therapy may be a better treatment for pancreatic cancer.
Additional locations may be listed on ClinicalTrials.gov for NCT02037230.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To determine the target dose and toxicity profile of AZD-1775 (WEE1 inhibitor AZD-1775) when administered concurrently with gemcitabine (gemcitabine hydrochloride) and gemcitabine-radiation in patients with unresectable pancreas adenocarcinoma.
SECONDARY OBJECTIVES:
I. To estimate the efficacy of this regimen (combined with standard systemic therapy) at the target dose, as determined by progression-free survival and overall survival at one year.
II. To determine if WEE1 G2 checkpoint kinase (Wee1) is inhibited by AZD-1775 at or below its target dose (with gemcitabine or gemcitabine-radiation) in surrogate tissues.
OUTLINE: This is a phase I, dose-escalation study of WEE1 inhibitor AZD1775 followed by a phase II study.
Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8 and WEE1 inhibitor AZD1775 orally (PO) once daily (QD) on days 1, 2, 8, and 9. Courses repeat every 21 days for up to 26 weeks (with a break in weeks 9-11) in the absence of disease progression or unacceptable toxicity. Patients also undergo intensity-modulated radiation therapy (IMRT) five days per week during weeks 4-8 for a total of 25 fractions.
After completion of study treatment, patients are followed up every 3 months for 18 months and then every 4 months for 18 months.
Lead OrganizationUniversity of Michigan Comprehensive Cancer Center
Principal InvestigatorTheodore Steven Lawrence
