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

Pancreatic Cancer Clinical Trial

Official title:

A Phase II Study of Preoperative Gemcitabine and Erlotinib Plus Pancreatectomy and Postoperative Gemcitabine and Erlotinib for Patients With Operable Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00733746
• Other study ID #: ACOSOG-Z5041
• Secondary ID: ACOSOG-Z5041U10C
• Status: Completed
• Phase: Phase 2
• Start date: April 2009
• Est. completion date: June 15, 2019

Study information

• Verified date: October 2019
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: June 15, 2019
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• erlotinib hydrochloride
oral administration
• gemcitabine hydrochloride
Intravenous administration

Procedure:
• therapeutic conventional surgery

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	St. Vincent's Medical Center	Bridgeport	Connecticut
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	St. Francis Hospital Cancer Care Services	Indianapolis	Indiana
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Lakeland Regional Cancer Center at Lakeland Regional Medical Center	Lakeland	Florida
United States	Kaiser Permanente Medical Center - Los Angeles	Los Angeles	California
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Surgical Oncology Associates	Newport News	Virginia
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
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

Sponsors (4)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	Astellas Pharma Inc, National Cancer Institute (NCI), OSI Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At 2 years post-registration
Secondary	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).	Up to 4 years postoperative chemotherapy treatment
Secondary	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.	At 2 years post-registration
Secondary	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.	Up to 4 years postoperative chemotherapy treatment
Secondary	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.	Up to 4 years postoperative chemotherapy treatment