Gemcitabine and Erlotinib Before and After Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery
|Pancreatic Cancer||Drug: erlotinib hydrochloride Drug: gemcitabine hydrochloride Procedure: therapeutic conventional surgery||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Preoperative Gemcitabine and Erlotinib Plus Pancreatectomy and Postoperative Gemcitabine and Erlotinib for Patients With Operable Pancreatic Adenocarcinoma|
- Overall Survival at 2 Years [ Time Frame: At 2 years post-registration ]The primary endpoint of this trial is 2-year overall survival, which will be evaluated as the proportion of treatment successes. A treatment success is defined to be an evaluable patient who is alive at two years from the date of registration.
- Resection Rate [ Time Frame: Up to 4 years postoperative chemotherapy treatment ]
The resection rate is defined as the fraction of patients that proceed to planned surgery with removal of primary tumor (R0/R1) following neoadjuvant treatment with gemcitabine plus erlotinib.The resection rate will be estimated by the binomial point estimate, i.e. as the number of patients that undergo the planned surgery with removal of the primary tumor following neoadjuvant treatment with gemcitabine plus erlotinib divided by the number of evaluable patients. This quantity will also be estimated with a 95% binomial confidence interval.
Curative resection (R0) is defined as macroscopically and microscopically complete resection (with microscopic surgical margin assessment according to AJCC Staging Principles).
An R1 resection is defined as macroscopically complete tumor removal with any positive microscopic surgical margin (bile duct, pancreatic parenchyma, or SMA margins).
- Relapse/Progression-free Survival [ Time Frame: At 2 years post-registration ]Relapse/progression-free survival is defined as the time from date of registration to the date of documentation of disease recurrence/progression. If a patient dies without documentation of disease recurrence/progression, the patient will be considered to have had disease recurrence/progression at the time of their death unless there is sufficient documented evidence to conclude no recurrence/progression occurred prior to death. If a patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation occurred. If a patient is lost to follow-up, s/he will be censored at the data of last contact. The distribution of disease-free survival will be estimated using the method of Kaplan and Meier.
- Number of Participants Experiencing Grade 3 or Higher Adverse Events as Graded by the NCI's Common Toxicity Criteria for Adverse Events [ Time Frame: Up to 4 years postoperative chemotherapy treatment ]The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns. These patterns will be summarized with descriptive statistics. The number of patients reporting grade 3 or higher adverse events as graded by the NCI's Common Toxicity Criteria (CTCAE) Version 4 are reported here. A complete list of all reported adverse events is reported in the Adverse Events section of this report.
- Response Rate [ Time Frame: Up to 4 years postoperative chemotherapy treatment ]The response rates to preoperative chemotherapy for patients treated with preoperative gemcitabine and erlotinib and rates of accurate pathologic assessment of the resected tumor specimen according to College of American Pathology guidelines will be estimated with a binomial point estimate and corresponding 95% confidence intervals.
|Study Start Date:||April 2009|
|Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Experimental: Neoadjuvant therapy + Surgery + Adjuvant therapy
As part of neoadjuvant therapy, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 15, 29, 36, and 43 and oral erlotinib hydrochloride once daily on days 1-43 in the absence of disease progression or unacceptable toxicity. Within 3-6 weeks after completion of neoadjuvant therapy, patients undergo pancreaticoduodenectomy and patients receive gemcitabine hydrochloride and erlotinib hydrochloride as in neoadjuvant therapy within 5-10 weeks post surgery.
Drug: erlotinib hydrochloride
oral administrationDrug: gemcitabine hydrochloride
Intravenous administrationProcedure: therapeutic conventional surgery
This is a single arm, non-randomized phase II study. Eligible, fully registered patients will receive preoperative chemotherapy consisting of gemcitabine plus erlotinib. Preoperative chemotherapy will be followed by exploratory laparotomy and pancreaticoduodenectomy. Patients will then receive postoperative chemotherapy consisting of gemcitabine plus erlotinib. Up to 123 patients will be accrued to this study, with the expectation that 78 patients will remain fully eligible and evaluable for the primary endpoint. The primary and secondary objectives for the study are listed below.
To estimate the proportion of patients alive at two years from the date of registration
- To determine the resection rate (defined as the fraction of patients who proceed to planned surgery with removal of primary tumor [R0/R1]) following induction treatment with gemcitabine plus erlotinib
- To estimate the time to disease progression/relapse
- To evaluate the rate of R0, R1, and R2 resections (defined as per the 6th edition of the AJCC Cancer Staging Manual) in patients treated with preoperative gemcitabine plus erlotinib chemotherapy
- To evaluate the toxicity profile of preoperative gemcitabine plus erlotinib and the feasibility of postoperative gemcitabine plus erlotinib
- To evaluate response rates to preoperative chemotherapy for patients treated with preoperative gemcitabine and erlotinib
- To identify molecular predictors of pancreatic cancer response to gemcitabine combined with erlotinib
- To identify genetic profiles of pancreatic adenocarcinoma that may be associated with response to neoadjuvant therapy
After completion of postoperative chemotherapy treatment, patients are followed every 3 months for 2 years and then every 6 months for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00733746
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|Study Chair:||Peter W.T. Pisters, MD||M.D. Anderson Cancer Center|