Phase II Study of Erlotinib (Tarceva) Combined With Chemoradiation and Adjuvant Chemotherapy in Patients With Resectable Pancreatic Cancer
- Determine the pharmacodynamic (inhibition of epidermal growth factor receptor [EGFR]
activation and signaling) effects of neoadjuvant erlotinib hydrochloride on tumor
tissue of patients with resectable stage I or II pancreatic adenocarcinoma.
- Determine, preliminarily, antitumor activity (progression-free survival) of adjuvant
erlotinib hydrochloride in combination with standard chemoradiotherapy comprising
capecitabine, gemcitabine hydrochloride, and radiotherapy after surgical resection in
- Characterize the toxicity profile of adjuvant erlotinib hydrochloride in combination
with standard chemoradiotherapy in these patients.
- Determine the pharmacodynamic (inhibition of EGFR activation and signaling) effects of
erlotinib hydrochloride on normal tissue (skin and oral mucosa) of patients receiving
erlotinib hydrochloride as adjuvant therapy.
- Characterize the pharmacokinetics of erlotinib hydrochloride (assessing both total and
unbound levels) given in combination with capecitabine and evaluate the association of
common allelic variants in candidate genes (EGFR, TS, DPD, MTHFR, and ORM1) with drug
disposition and toxicity.
- Determine the relationships between pharmacodynamic effects and patient outcome.
- Assess the value of PET/CT scanning as a predictor of response to erlotinib
hydrochloride treatment in patients with pancreatic cancer.
- Evaluate the benefit of fusing PET/CT scans together with the radiation treatment
planning CT scan.
- Determine if the Active Breathing Coordinator (ABC) minimizes the effects of
respiratory motion during radiation treatment and results in better radiation coverage
of the tumor bed and adjacent lymph nodes.
OUTLINE: This is a randomized, placebo-controlled study.
- Neoadjuvant therapy: Patients are randomized to 1 of 2 neoadjuvant treatment arms.
- Arm I: Patients receive oral erlotinib hydrochloride once a day for 3-5 days.
Patients then proceed to surgery.
- Arm II: Patients receive oral placebo once a day for 3-5 days. Patients then
proceed to surgery.
- Surgery: Patients undergo surgical resection. Patients then proceed to adjuvant
- Adjuvant therapy: Patients receive oral capecitabine twice a day and oral erlotinib
hydrochloride once a day for 5½ weeks. Patients also undergo concurrent radiotherapy 5
days a week for 5½ weeks. Beginning 6 weeks later, patients receive gemcitabine
hydrochloride IV on days 1, 8, and 15 and oral erlotinib hydrochloride once daily on
days 1-28. Treatment with gemcitabine hydrochloride and erlotinib hydrochloride repeats
every 28 days for 4 courses.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Allocation: Randomized, Primary Purpose: Treatment
Pharmacodynamics of neoadjuvant erlotinib
Joseph Herman, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Federal Government
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|