Back to resultsGemcitabine and Erlotinib Before and After Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery
Primary Purpose
Pancreatic Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
erlotinib hydrochloride
gemcitabine hydrochloride
therapeutic conventional surgery
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring adenocarcinoma of the pancreas, stage I pancreatic cancer, stage II pancreatic cancer
Eligibility Criteria
Eligibility Criteria:
Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinate process.
NOTE: Patients with tumors of the pancreatic neck, body or tail are not eligible. Patients with evidence of neuroendocrine tumors, duodenal adenocarcinoma, or ampullary adenocarcinoma are not eligible.
Localized, potentially resectable tumors as defined below. All patients must be staged with a chest X-ray or CT, and abdominal CT (contrast-enhanced, helical thin-cut) or MRI. Radiological resectability is defined by the following criteria on abdominal imaging:
- No evidence of tumor extension to the celiac axis, hepatic artery, or superior mesenteric artery
- No evidence of tumor encasement or occlusion of the superior mesenteric vein (SMV) or the SMV/portal vein confluence
- No evidence of visceral or peritoneal metastases
NOTE: Patients with borderline resectable or marginally resectable pancreatic cancer are not eligible. Patients must meet all objective imaging criteria outlined above.
- ≥ 18 years of age
- ECOG/Zubrod performance status of 0 or 1
- Baseline weight loss ≤ 15% of premorbid weight
Patient must have adequate hematologic, renal, and hepatic function as defined by:
- WBC ≥ 2,000 cells/mm³
- ANC ≥ 1,500 cells/mm³
- Platelets ≥ 100,000 cells/mm³
- Serum bilirubin ≤ 2.5 mg/dL
- Serum creatinine ≤ 1.5 mg/dL or a calculated creatinine clearance of ≥ 50 ml/min (24 hour urine collection)
- ALT < 2.5 times upper limit of normal (ULN)
- AST < 2.5 times ULN
- Albumin ≥ 3.2 g/dl
No history of the following:
- Prior EGFR targeted therapy or therapy for pancreatic cancer
- Active infection requiring intravenous antibiotics at the time of registration
- Non-pregnant and non-breast feeding. Female participants of child bearing potential must have a negative urine or serum pregnancy test prior to registration. Perimenopausal participants must be amenorrheic ≥ 12 months to be considered not of childbearing potential. All patients of reproductive potential must agree to use an effective method of birth control while receiving study therapy.
- No prior malignancy within 5 years of registration (Exceptions: non-melanoma skin cancer, in-situ cancers)
Sites / Locations
- Rebecca and John Moores UCSD Cancer Center
- Kaiser Permanente Medical Center - Los Angeles
- Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
- St. Vincent's Medical Center
- Lakeland Regional Cancer Center at Lakeland Regional Medical Center
- St. Francis Hospital Cancer Care Services
- Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
- St. Agnes Hospital Cancer Center
- University of Mississippi Cancer Clinic
- Methodist Estabrook Cancer Center
- NYU Cancer Institute at New York University Medical Center
- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
- David L. Rike Cancer Center at Miami Valley Hospital
- Samaritan North Cancer Care Center
- CCOP - Dayton
- Charles F. Kettering Memorial Hospital
- UVMC Cancer Care Center at Upper Valley Medical Center
- Natalie Warren Bryant Cancer Center at St. Francis Hospital
- Providence Cancer Center at Providence Portland Medical Center
- Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
- Surgical Oncology Associates
- Mary Babb Randolph Cancer Center at West Virginia University Hospitals
- University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
- Princess Margaret Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Neoadjuvant therapy + Surgery + Adjuvant therapy
Arm Description
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.
Outcomes
Primary Outcome Measures
Overall Survival at 2 Years
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
Resection Rate
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
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
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
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.
Full Information
NCT ID
NCT00733746
First Posted
August 12, 2008
Last Updated
October 4, 2019
Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI), OSI Pharmaceuticals, Astellas Pharma Inc
1. Study Identification
Unique Protocol Identification Number
NCT00733746
Brief Title
Gemcitabine and Erlotinib Before and After Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery
Official Title
A Phase II Study of Preoperative Gemcitabine and Erlotinib Plus Pancreatectomy and Postoperative Gemcitabine and Erlotinib for Patients With Operable Pancreatic Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
April 2009 (Actual)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
June 15, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI), OSI Pharmaceuticals, Astellas Pharma Inc
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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:
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
adenocarcinoma of the pancreas, stage I pancreatic cancer, stage II pancreatic cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
123 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Neoadjuvant therapy + Surgery + Adjuvant therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
erlotinib hydrochloride
Intervention Description
oral administration
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Intervention Description
Intravenous administration
Intervention Type
Procedure
Intervention Name(s)
therapeutic conventional surgery
Primary Outcome Measure Information:
Title
Overall Survival at 2 Years
Description
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.
Time Frame
At 2 years post-registration
Secondary Outcome Measure Information:
Title
Resection Rate
Description
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).
Time Frame
Up to 4 years postoperative chemotherapy treatment
Title
Relapse/Progression-free Survival
Description
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.
Time Frame
At 2 years post-registration
Title
Number of Participants Experiencing Grade 3 or Higher Adverse Events as Graded by the NCI's Common Toxicity Criteria for Adverse Events
Description
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.
Time Frame
Up to 4 years postoperative chemotherapy treatment
Title
Response Rate
Description
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.
Time Frame
Up to 4 years postoperative chemotherapy treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Eligibility Criteria:
Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinate process.
NOTE: Patients with tumors of the pancreatic neck, body or tail are not eligible. Patients with evidence of neuroendocrine tumors, duodenal adenocarcinoma, or ampullary adenocarcinoma are not eligible.
Localized, potentially resectable tumors as defined below. All patients must be staged with a chest X-ray or CT, and abdominal CT (contrast-enhanced, helical thin-cut) or MRI. Radiological resectability is defined by the following criteria on abdominal imaging:
No evidence of tumor extension to the celiac axis, hepatic artery, or superior mesenteric artery
No evidence of tumor encasement or occlusion of the superior mesenteric vein (SMV) or the SMV/portal vein confluence
No evidence of visceral or peritoneal metastases
NOTE: Patients with borderline resectable or marginally resectable pancreatic cancer are not eligible. Patients must meet all objective imaging criteria outlined above.
≥ 18 years of age
ECOG/Zubrod performance status of 0 or 1
Baseline weight loss ≤ 15% of premorbid weight
Patient must have adequate hematologic, renal, and hepatic function as defined by:
WBC ≥ 2,000 cells/mm³
ANC ≥ 1,500 cells/mm³
Platelets ≥ 100,000 cells/mm³
Serum bilirubin ≤ 2.5 mg/dL
Serum creatinine ≤ 1.5 mg/dL or a calculated creatinine clearance of ≥ 50 ml/min (24 hour urine collection)
ALT < 2.5 times upper limit of normal (ULN)
AST < 2.5 times ULN
Albumin ≥ 3.2 g/dl
No history of the following:
Prior EGFR targeted therapy or therapy for pancreatic cancer
Active infection requiring intravenous antibiotics at the time of registration
Non-pregnant and non-breast feeding. Female participants of child bearing potential must have a negative urine or serum pregnancy test prior to registration. Perimenopausal participants must be amenorrheic ≥ 12 months to be considered not of childbearing potential. All patients of reproductive potential must agree to use an effective method of birth control while receiving study therapy.
No prior malignancy within 5 years of registration (Exceptions: non-melanoma skin cancer, in-situ cancers)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter W.T. Pisters, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Rebecca and John Moores UCSD Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
Kaiser Permanente Medical Center - Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
St. Vincent's Medical Center
City
Bridgeport
State/Province
Connecticut
ZIP/Postal Code
06606
Country
United States
Facility Name
Lakeland Regional Cancer Center at Lakeland Regional Medical Center
City
Lakeland
State/Province
Florida
ZIP/Postal Code
33805
Country
United States
Facility Name
St. Francis Hospital Cancer Care Services
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Facility Name
St. Agnes Hospital Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21229
Country
United States
Facility Name
University of Mississippi Cancer Clinic
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Methodist Estabrook Cancer Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
NYU Cancer Institute at New York University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7295
Country
United States
Facility Name
David L. Rike Cancer Center at Miami Valley Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
Samaritan North Cancer Care Center
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45415
Country
United States
Facility Name
CCOP - Dayton
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45420
Country
United States
Facility Name
Charles F. Kettering Memorial Hospital
City
Kettering
State/Province
Ohio
ZIP/Postal Code
45429
Country
United States
Facility Name
UVMC Cancer Care Center at Upper Valley Medical Center
City
Troy
State/Province
Ohio
ZIP/Postal Code
45373-1300
Country
United States
Facility Name
Natalie Warren Bryant Cancer Center at St. Francis Hospital
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
Providence Cancer Center at Providence Portland Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213-2967
Country
United States
Facility Name
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
Facility Name
Surgical Oncology Associates
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23606
Country
United States
Facility Name
Mary Babb Randolph Cancer Center at West Virginia University Hospitals
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792-6164
Country
United States
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Gemcitabine and Erlotinib Before and After Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery
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