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

NCT ID: NCT00733746

Last Updated: 2019-10-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2019-06-15

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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant therapy + Surgery + Adjuvant therapy

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.

Group Type: EXPERIMENTAL

erlotinib hydrochloride

Intervention Type: DRUG

oral administration

gemcitabine hydrochloride

Intervention Type: DRUG

Intravenous administration

therapeutic conventional surgery

Intervention Type: PROCEDURE

Interventions

erlotinib hydrochloride

oral administration

Intervention Type: DRUG

gemcitabine hydrochloride

Intravenous administration

Intervention Type: DRUG

therapeutic conventional surgery

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

OSI Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Astellas Pharma Inc

INDUSTRY

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter W.T. Pisters, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

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

St. Francis Hospital Cancer Care Services

Indianapolis, Indiana, United States

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, United States

St. Agnes Hospital Cancer Center

Baltimore, Maryland, United States

University of Mississippi Cancer Clinic

Jackson, Mississippi, United States

Methodist Estabrook Cancer Center

Omaha, Nebraska, United States

NYU Cancer Institute at New York University Medical Center

New York, New York, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, United States

Samaritan North Cancer Care Center

Dayton, Ohio, United States

CCOP - Dayton

Dayton, Ohio, United States

Charles F. Kettering Memorial Hospital

Kettering, Ohio, 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

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

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

Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

Other Identifiers

ACOSOG-Z5041

Identifier Type: -

Identifier Source: secondary_id

U10CA076001

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00348

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000609871

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACOSOG-Z5041

Identifier Type: -

Identifier Source: org_study_id