A Phase I, Open-Label, Two-stage, Randomized, Crossover, Comparative Pharmacokinetic and Safety Study of Two Formulations of CO-1.01 for Injection in Patients With Advanced Solid Tumors
Gemcitabine is used alone or in combination with other chemotherapy as a treatment for
several solid tumor types, including pancreatic cancer, NSCLC, and ovarian cancer.
Unfortunately, many patients fail to derive benefit from this treatment. No clinical or
molecular marker has been established to predict benefit from gemcitabine therapy, so
patients are treated empirically until evidence of disease progression or worsening
performance status.
The potential for human equilibrative nucleoside transporter-1 (hENT1) expression to predict
survival in gemcitabine-treated patients has been studied, and data suggest that patients
with low levels of tumor cell hENT1 expression derive less benefit from gemcitabine
treatment than patients with high levels of tumor cell hENT1 expression. Furthermore, the
PK profiles of CO-1.01 and gemcitabine are different, and this may also favorably influence
the in vivo antiproliferative effects of CO-1.01. These data support the hypothesis that
patients expressing low levels of hENT1 will derive minimal benefit from gemcitabine, but
will receive benefit from CO-1.01 (gemcitabine elaidate) which enters tumor cells in a
hENT1-independent fashion.
The formulation of CO-1.01 that is currently used in clinical studies contains 15 mg/mL of
gemcitabine-5'-elaidate solubilized in purified phospholipids. Recently, Clovis Oncology
developed a 30 mg/ml formulation which will be characterized in this study.
Interventional
Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Ratio of the AUC0-∞ of the two formulations of CO-1.01 given as a 30 min i.v. infusion at 1250 mg/m2
Serum & urine PK sampling at multiple timepoints through Cycle 1: Day 1 & Day 8
No
Jan Schellens, MD PhD
Principal Investigator
The Netherlands Cancer Institute, Amsterdam, Netherlands
United States: Food and Drug Administration
CO-101-004
NCT01392976
April 2011
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