MC0748, Phase I/II Study of LY2090314 and Gemcitabine or FOLFOX in Untreated, Metastatic Pancreatic Cancer Patients With Metastases Amenable to Biopsy.
I. To determine the LY2090314 dose which results in significant inhibition of the biologic
target, glycogen synthase kinase-3 beta (GSK-3β), when administered with gemcitabine (Cohort
I) or FOLFOX (Cohort II) chemotherapy.
I. To assess clinical activity in the two cohorts as measured by 6-month survival, overall
survival, progression-free survival, confirmed response rate, and toxicity.
I. Correlate the relationship between GSK-3 inhibition and clinical activity. II. Detect
GSK-3 inhibition in tumor and surrogate specimens (peripheral blood mononuclear cells
[PBMCs]) and compare between observed GSK-3 inhibition among the specimens.
III. Blood will be collected for banking of plasma, serum and buffy coat. IV. Plasma samples
will be collected for pharmacokinetic (PK) analyses
OUTLINE: This is a phase I study followed by a phase II study.
COHORT I: Patients receive LY2090314 intravenously (IV) over 60 minutes on days 0, 8, and 15
of course 1 and on days 1, 8, and 15 of all subsequent courses. Patients also receive
gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every
28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients receive LY2090314 IV over 60 minutes on days 0 and 15 of course 1 and on
days 1 and 15 of all subsequent courses. Patients also receive FOLFOX chemotherapy
comprising leucovorin calcium IV over 2 hours, fluorouracil IV continuously over 46 hours,
and oxaliplatin IV over 2 hours on days 1and 15. Treatment repeats every 28 days for up to 2
years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Biological activity assessment defined as the change in the phosphorylation level of glycogen synthase, a direct GSK3beta target using tumor tissue and blood specimens
A paired t-test (or non-parametric equivalent) will be used to see if there is an overall decrease from baseline to any day post-baseline in these patients.
From baseline to 4 hours post-treatment on day 0
United States: Food and Drug Administration
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