Gemcitabine and Erlotinib Before and After Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery
- Conditions
- Pancreatic Cancer
- Interventions
- Procedure: therapeutic conventional surgery
- Registration Number
- NCT00733746
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
PURPOSE: This phase II trial is studying how well gemcitabine and erlotinib work when given before and after surgery in treating patients with pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine and erlotinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these drugs after surgery may kill any tumor cells that remain after surgery.
- Detailed Description
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.
Primary Objective:
To estimate the proportion of patients alive at two years from the date of registration
Secondary Objectives:
1. 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
2. To estimate the time to disease progression/relapse
3. 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
4. To evaluate the toxicity profile of preoperative gemcitabine plus erlotinib and the feasibility of postoperative gemcitabine plus erlotinib
5. To evaluate response rates to preoperative chemotherapy for patients treated with preoperative gemcitabine and erlotinib
6. To identify molecular predictors of pancreatic cancer response to gemcitabine combined with erlotinib
7. 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 123
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Neoadjuvant therapy + Surgery + Adjuvant therapy erlotinib hydrochloride 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. Neoadjuvant therapy + Surgery + Adjuvant therapy gemcitabine hydrochloride 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. Neoadjuvant therapy + Surgery + Adjuvant therapy therapeutic conventional surgery 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.
- Primary Outcome Measures
Name Time Method Overall Survival at 2 Years 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.
- Secondary Outcome Measures
Name Time Method Relapse/Progression-free Survival 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 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 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.
Resection Rate 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).
Trial Locations
- Locations (24)
Rebecca and John Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
🇺🇸Orange, California, United States
Lakeland Regional Cancer Center at Lakeland Regional Medical Center
🇺🇸Lakeland, Florida, United States
St. Agnes Hospital Cancer Center
🇺🇸Baltimore, Maryland, United States
NYU Cancer Institute at New York University Medical Center
🇺🇸New York, New York, United States
University of Mississippi Cancer Clinic
🇺🇸Jackson, Mississippi, United States
Charles F. Kettering Memorial Hospital
🇺🇸Kettering, Ohio, United States
Kaiser Permanente Medical Center - Los Angeles
🇺🇸Los Angeles, California, United States
St. Vincent's Medical Center
🇺🇸Bridgeport, Connecticut, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
🇺🇸Baltimore, Maryland, United States
UVMC Cancer Care Center at Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
Natalie Warren Bryant Cancer Center at St. Francis Hospital
🇺🇸Tulsa, Oklahoma, United States
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
🇺🇸Spartanburg, South Carolina, United States
Surgical Oncology Associates
🇺🇸Newport News, Virginia, United States
Mary Babb Randolph Cancer Center at West Virginia University Hospitals
🇺🇸Morgantown, West Virginia, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
St. Francis Hospital Cancer Care Services
🇺🇸Indianapolis, Indiana, United States
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
CCOP - Dayton
🇺🇸Dayton, Ohio, United States
Providence Cancer Center at Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Methodist Estabrook Cancer Center
🇺🇸Omaha, Nebraska, United States
David L. Rike Cancer Center at Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Samaritan North Cancer Care Center
🇺🇸Dayton, Ohio, United States