Clinical trial NCT00733746: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: adenocarcinoma of the pancreas
stage I pancreatic cancer
stage II pancreatic cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: OSI Pharmaceuticals
name: Astellas Pharma Inc
First posted: 2008-08-13
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Overall Survival at 2 Years
timeFrame: At 2 years post-registration
Secondary outcomes:
measure: Resection Rate
timeFrame: Up to 4 years postoperative chemotherapy treatment
measure: Relapse/Progression-free Survival
timeFrame: At 2 years post-registration
measure: Number of Participants Experiencing Grade 3 or Higher Adverse Events as Graded by the NCI's Common Toxicity Criteria for Adverse Events
timeFrame: Up to 4 years postoperative chemotherapy treatment
measure: Response Rate
timeFrame: Up to 4 years postoperative chemotherapy treatment
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Medical Center - Los Angeles
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
state: California
city: Bridgeport
country: United States
facility: St. Vincent's Medical Center
state: Connecticut
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center at Lakeland Regional Medical Center
state: Florida
city: Indianapolis
country: United States
facility: St. Francis Hospital Cancer Care Services
state: Indiana
city: Baltimore
country: United States
facility: Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
state: Maryland
city: Baltimore
country: United States
facility: St. Agnes Hospital Cancer Center
state: Maryland
city: Jackson
country: United States
facility: University of Mississippi Cancer Clinic
state: Mississippi
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: New York
country: United States
facility: NYU Cancer Institute at New York University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at St. Francis Hospital
state: Oklahoma
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Newport News
country: United States
facility: Surgical Oncology Associates
state: Virginia
city: Morgantown
country: United States
facility: Mary Babb Randolph Cancer Center at West Virginia University Hospitals
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Peter W.T. Pisters, MD
role: STUDY_CHAIR
References: