Safety and Pharmacokinetic Profiles of Two Formulations of CO-1.01 in Patients With Advanced Solid Tumors
|Advanced Solid Tumor||Drug: CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids) Drug: CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids)||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||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|
- Ratio of the AUC0-∞ of the two formulations of CO-1.01 given as a 30 min i.v. infusion at 1250 mg/m2 [ Time Frame: Serum & urine PK sampling at multiple timepoints through Cycle 1: Day 1 & Day 8 ]
- PK of CO-1.01 and metabolites in plasma and urine after 1250 mg/m2 CO-1.01 given as a single 30 min i.v. infusion [ Time Frame: Serum & urine PK sampling at multiple timepoints through Cycle 1: Day 1 & Day 8 ]
- QT/QTc interval of the ECG [ Time Frame: Continuous ECG monitoring 8 hrs pre & post dose C1: D1, D8. 12 lead ECGs pre-dose, 30mins, 24hr, 48hr, 72hr C1: D1, D8 ]
- Relationship between plasma concentration of CO-1.01 and QT/QTc interval of the ECG [ Time Frame: Plasma: multiple timepoints through C1D1 and D8. ECG: continuous monitoring 8 hrs pre & post dose C1: D1, D8. 12 lead ECGs pre-dose, 30mins, 24hr, 48hr, 72hr C1:D1, D8. ]
- Drug tolerability and toxicity using clinical AE monitoring and clinical laboratory testing [ Time Frame: From the time of signing the ICF until 28 days after last dose of CO-101. CO-101 dosed on C1D1, C1D8, C1D15, C2D1, C2D8, and C2D15. ]
|Study Start Date:||April 2011|
|Study Completion Date:||April 2013|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
|Experimental: CO-1.01 Formulation B||
Drug: CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids)
1250 mg/m2 intravenous infusion on Day 1 for Treatment Sequence 2 and Day 8 for Treatment Sequence 1.
|Active Comparator: CO-1.01 Formulation A||
Drug: CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids)
1250 mg/m2 intravenous infusion on Day 1 for Treatment Sequence 1 and Day 8 for Treatment Sequence 2.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01392976
|The Netherlands Cancer Institute|
|Amsterdam, Netherlands, 1066 CX|
|Maastricht University Medical Center|
|Maastricht, Netherlands, 6229 HX|
|University Medical Center Utrecht|
|Utrecht, Netherlands, 3584 CX|
|Principal Investigator:||Jan Schellens, MD PhD||The Netherlands Cancer Institute, Amsterdam, Netherlands|