Erlotinib, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Stage I or Stage II Pancreatic Cancer That Can Be Removed By Surgery
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Drugs used in chemotherapy, such as capecitabine and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib together with combination chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This randomized phase II trial is studying how well giving erlotinib before and after surgery together with combination chemotherapy and radiation therapy works in treating patients with stage I or stage II pancreatic cancer that can be removed by surgery.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
|Official Title:||Phase II Study of Erlotinib (Tarceva) Combined With Chemoradiation and Adjuvant Chemotherapy in Patients With Resectable Pancreatic Cancer|
- Pharmacodynamics of neoadjuvant erlotinib [ Designated as safety issue: No ]
- Antitumor activity of adjuvant therapy (erlotinib hydrochloride, capecitabine, gemcitabine hydrochloride, and radiotherapy) following surgical resection [ Designated as safety issue: No ]
- Toxicity profile of adjuvant therapy [ Designated as safety issue: Yes ]
- Pharmacodynamic effects of adjuvant erlotinib hydrochloride on normal tissue [ Designated as safety issue: No ]
- Pharmacokinetics of erlotinib hydrochloride and capecitabine [ Designated as safety issue: No ]
- Allelic variants in candidate genes (EGFR, TS, DPD, MTHFR, and ORM1) as related to drug disposition and toxicity [ Designated as safety issue: Yes ]
- Correlate pharmacodynamics and patient outcomes [ Designated as safety issue: No ]
- Predicted response by positron-emission tomography (PET)/CT scan [ Designated as safety issue: No ]
- Benefit of fusing PET/CT scans together with the radiotherapy planning CT scan [ Designated as safety issue: No ]
- Decreased respiratory motion during radiation treatment and better radiation coverage by using the Active Breathing Coordinator [ Designated as safety issue: No ]
|Study Start Date:||January 2006|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive oral erlotinib hydrochloride once a day for 3-5 days. Patients then proceed to surgery.
Drug: erlotinib hydrochloride
Placebo Comparator: Arm II
Patients receive oral placebo once a day for 3-5 days. Patients then proceed to surgery.
- 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 these patients.
- 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 therapy.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00313560
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|Study Chair:||Joseph Herman, MD||Sidney Kimmel Comprehensive Cancer Center|