A Phase I Dose-Escalating Study of Induction Gemcitabine/Pemetrexed Followed by Pemetrexed and Concurrent Upper Abdominal Radiation Therapy in Patients With Locally Advanced Pancreatic Cancer
- Determine the maximum tolerated dose of pemetrexed disodium when given in combination
with upper abdominal radiotherapy after induction therapy comprising gemcitabine
hydrochloride and pemetrexed disodium followed by consolidation therapy with
gemcitabine hydrochloride in patients with locally advanced pancreatic cancer.
- Determine the quantitative toxicity of this regimen in these patients.
- Determine the quantitative and qualitative dose-limiting toxicities of pemetrexed
disodium in combination with upper abdominal radiation therapy.
- Evaluate patterns of failure, response, and survival of these patients at 1 year
OUTLINE: This is an open-label, nonrandomized, dose-escalation study of pemetrexed disodium.
- Induction therapy: Patients receive pemetrexed disodium IV over 10 minutes and
gemcitabine hydrochloride IV over 30 minutes on day 1. Treatment repeats every 14 days
for 3 courses. Approximately 2 weeks later, patients without disease progression
proceed to chemoradiotherapy.
- Chemoradiotherapy: Patients receive pemetrexed disodium IV over 10 minutes on days 1,
15, and 29 and undergo radiotherapy once daily 5 days a week for 5 ½ weeks.
Approximately 2-3 weeks later, patients without disease progression proceed to
Cohorts of 3-9 patients receive escalating doses of pemetrexed disodium during
chemoradiotherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined
as the dose at which ≤ 20% or ≤ 2 of 9 patients experience dose-limiting toxicity.
- Consolidation therapy: Patients receive gemcitabine hydrochloride IV over 30 minutes on
days 1 and 8. Treatment repeats every 21 days for 2 courses in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
determine maximum tolerated dose of Premetrexed wehen given concurrently with gemcitabine
Arthur William Blackstock, MD
Comprehensive Cancer Center of Wake Forest University
United States: Institutional Review Board
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|