Gemcitabine and Erlotinib Before and After Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery

Alliance for Clinical Trials in Oncology123 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Eligibility Criteria: 1. 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. 2. 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. 3. ≥ 18 years of age 4. ECOG/Zubrod performance status of 0 or 1 5. Baseline weight loss ≤ 15% of premorbid weight 6. 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 7. No history of the following: * Prior EGFR targeted therapy or therapy for pancreatic cancer * Active infection requiring intravenous antibiotics at the time of registration 8. 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. 9. No prior malignancy within 5 years of registration (Exceptions: non-melanoma skin cancer, in-situ cancers)

Locations (24)

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States

Kaiser Permanente Medical Center - Los Angeles

Los Angeles, California, United States

Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center

Orange, California, United States

St. Vincent's Medical Center

Bridgeport, Connecticut, United States

Lakeland Regional Cancer Center at Lakeland Regional Medical Center

Lakeland, Florida, United States

Outcomes

Primary Outcomes

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.

Time frame: At 2 years post-registration

Secondary Outcomes

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).

Time frame: Up to 4 years postoperative chemotherapy treatment

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.

Time frame: At 2 years post-registration

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.

Time frame: Up to 4 years postoperative chemotherapy treatment

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.

Time frame: Up to 4 years postoperative chemotherapy treatment

Gemcitabine and Erlotinib Before and After Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery

Overview

Conditions

Interventions

Eligibility

Locations (24)

Outcomes

Primary Outcomes

Secondary Outcomes