Immunotherapy Study for Surgically Resected Pancreatic Cancer

NCT ID: NCT01072981

Last Updated: 2020-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 722 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2016-05-31

Brief Summary

The purpose of this study is to assess overall survival after treatment with a regimen of adjuvant therapy (Gemcitabine alone or with 5-FU chemoradiation) with or without HyperAcute®-Pancreas (algenpantucel-L) immunotherapy in subjects who have undergone surgical resection.

Detailed Description

Unfortunately, despite the best clinical efforts and breakthroughs in biotechnology, most patients diagnosed with pancreatic cancer continue to die from the rapid progression of their disease. The primary reason for this is that the disease is typically without symptoms until significant local and/or distant spread has occurred and is often beyond the chance for cure at the time of the diagnosis. The lack of any treatment to significantly increase long term survival rates is reflected by the poor outcomes associated with this disease, specifically time to disease progression and overall survival.

These disappointing facts typically shape discussions of treatment options for patients with this disease. However, another important part of the body is now being looked at as a target for therapy against this disease -- the immune system. Scientists have clearly shown that pancreatic tumor cells produce a number of defective proteins, or express normal proteins in highly uncharacteristic ways, as part of this cancer. In some cancers, these abnormalities can cause an immune response to the cancer cells much in the way one responds to infected tissue. In progressive cancers however, the immune system fails to identify or respond to these abnormalities and the cancer cells are not attacked or destroyed for reasons not yet fully understood. This clinical trial proposes a new way to stimulate the immune system to recognize the abnormal components found in pancreatic cancer cells and to stimulate an immune response that destroys or blocks the growth of the cancer.

This new method of treatment helps the immune system of pancreatic cancer patients to "identify" the cancerous tissue so that it can be eliminated from the body. As an example, most people are aware that patients with certain diseases may require an organ transplant to replace a damaged kidney or heart. After receiving their transplant these patients receive special drugs because they are at great danger of having an immune response that destroys or "rejects" the transplanted organ. This "rejection" occurs when their immune system responds to differences between the cells of the transplanted organ and their own immune system by attacking the foreign tissue in the same way as it would attack infected tissue. When the differences between foreign tissues and the patient's body are even larger, perhaps like differences between organs from pigs and the immune system cells of humans, the rejection is very rapid, highly destructive and the immunity it generates is long lasting. This is called hyperacute rejection and the medicine used to immunize patients in this protocol tries to harness this response to teach a patient's immune system to fight their pancreatic cancer just as the body would learn to reject a transplanted organ from an animal.

To do this, the investigators have placed a mouse gene into human pancreatic cancer cells so that the immune system will easily recognize them as foreign, stimulating the patient immune system to attack the vaccine cells just as they would any other animal cells. As part of the process of destroying the immunotherapy cells, the patient immune system is stimulated to identify as many differences from normal human as possible. This extra stimulation is thought to encourage immune responses against the pancreatic cancer in the patient based on shared abnormalities of pancreatic cancer vaccine cells and the patient's pancreatic cancer cells.

In this experimental therapy, patients are given injections of an immunotherapy consisting of two types of cancer cells that the investigators have modified to make them more easily recognized and attacked by the immune system. The investigators propose to test this new treatment in patients with pancreatic cancer who have undergone tumor removal surgery but remain at extremely high risk of disease progression to demonstrate that treatment with the immunotherapy increases the time until the tumor recurs or increases overall survival when given in combination with the current standard of care therapy for this disease.

For more information, please see our study specific website: www.pancreaticcancer-clinicaltrials.com

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HyperAcute-Pancreas Immunotherapy + Standard of Care

\*Adjuvant Standard of Care Treatment (SOC) consisting of gemcitabine with or without 5FU chemoradiation + HyperAcute Immunotherapy

Group Type: EXPERIMENTAL

HyperAcute-Pancreas Immunotherapy

Intervention Type: BIOLOGICAL

Up to 18 immunizations of 300 million immunotherapy cells

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000 mg/m2/day once a week for 3 weeks

5FU Chemoradiation

Intervention Type: RADIATION

5FU 200-250 mg/m2/day over 5 1/2 weeks with radiation.

Standard of Care alone

\*Adjuvant Standard of Care Treatment (SOC) consisting of gemcitabine with or without 5FU chemoradiation Alone

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000 mg/m2/day once a week for 3 weeks

5FU Chemoradiation

Intervention Type: RADIATION

5FU 200-250 mg/m2/day over 5 1/2 weeks with radiation.

Interventions

HyperAcute-Pancreas Immunotherapy

Up to 18 immunizations of 300 million immunotherapy cells

Intervention Type: BIOLOGICAL

Gemcitabine

Gemcitabine 1000 mg/m2/day once a week for 3 weeks

Intervention Type: DRUG

5FU Chemoradiation

5FU 200-250 mg/m2/day over 5 1/2 weeks with radiation.

Intervention Type: RADIATION

Other Intervention Names

HAPa-1 and HAPa-2 immunotherapy components; Gemzar; Fluorouracil

Eligibility Criteria

Inclusion Criteria

• A histological diagnosis of adenocarcinoma of the pancreas confirmed by pathology.
• American Joint Committee on Cancer (AJCC) Stage I or II Pancreatic carcinoma. Patients must have undergone surgical resection for the tumor and extent of resection must be either R0 (complete resection with grossly and microscopically negative margins of resection) or R1 (grossly negative but positive microscopically margins of resection).
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Serum albumin ≥2.0 gm/dL.
• Expected survival ≥6 months.
• Subjects must be able to take in adequate daily calorie intake based on judgment of clinical investigator.
• Adequate organ function including:
• A. Marrow: white blood cells (WBC) ≥3000/mm3 and platelets ≥100,000/mm3.
• B. Hepatic: serum total bilirubin ≤2 x ULN mg/dL, ALT (SGPT) and AST (SGOT) ≤3 x upper limit of normal (ULN).
• C. Renal: serum creatinine (sCr) ≤2.0 x ULN, or creatinine clearance (Ccr) ≥30 mL/min.
• First vaccination must be within 10 weeks after surgery.
• Patients must have the ability to understand the study, its inherent risks, side effects and potential benefits and be able to give written informed consent to participate. Patients may not be consented by a durable power of attorney (DPA).
• All subjects of child producing potential must agree to use contraception or avoidance of pregnancy measures while enrolled on study and receiving the experimental product, and for one month after the last immunization.

Exclusion Criteria

• Age <18-years-old.
• Active metastases. Suspicious lesions on CT scans must be reviewed by a second, different reviewer. If active disease not ruled out by second, different reviewer (at clinical institution), a positron emission tomography (PET) CT or further imaging tests or histology may be needed to rule out disease before enrollment is allowed.
• Other malignancy within five years, unless the probability of recurrence of the prior malignancy is <5% as determined by the Principal Investigator based on available information. Patient's curatively treated for squamous and basal cell carcinoma of the skin or patients with a history of malignant tumor in the past that have been disease free for at least five years are also eligible for this study.
• History of organ transplant.
• Current, active immunosuppressive therapy such as cyclosporine, tacrolimus, etc.
• Subjects taking chronic systemic corticosteroid therapy for any reason are not eligible. Subjects may receive steroids as prophylactic anti-emetics, not to exceed 10 mg Decadron weekly. Subjects may also receive pulse doses for Gemcitabine hypersensitivity, not to exceed Decadron 8 mg twice a day (BID) x 3 days prior to start day of Gemcitabine. Subjects receiving inhaled or topical corticosteroids are eligible. Subjects who require chronic systemic corticosteroids after beginning vaccination, will be removed from study.
• Significant or uncontrolled congestive heart failure (CHF),myocardial infarction or significant ventricular arrhythmias within the last six months.
• Active infection or antibiotics within 48 hours prior to study,including unexplained fever (temp > 38.1C).
• Autoimmune disease (e.g., systemic lupus erythematosis (SLE), rheumatoid arthritis (RA), etc.). Patients with a remote history of asthma or mild active asthma are eligible.
• Other serious medical conditions that may be expected to limit life expectancy to less than 2 years (e.g., liver cirrhosis) or a serious illness in medical opinion of the clinical investigator.
• Any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc.).
• A known allergy to any component of the HyperAcute® immunotherapy.
• Pregnant or nursing women due to the unknown effects of vaccination on the developing fetus or newborn infant. (For patients with child bearing potential, a βHCG must be completed within 14 days of first vaccination).
• Known HIV positive.

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

Sponsors

NewLink Genetics Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama

Birmingham, Alabama, United States

University of South Alabama

Mobile, Alabama, United States

Arizona Cancer Center

Tucson, Arizona, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

City of Hope National Medical Center

Duarte, California, United States

University of Southern California

Los Angeles, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

Stanford Cancer Center

Palo Alto, California, United States

Sutter Institute for Medical Research

Sacramento, California, United States

California Pacific Medical Center

San Francisco, California, United States

University of Colorado

Aurora, Colorado, United States

Stamford Hospital

Stamford, Connecticut, United States

Georgetown University

Washington D.C., District of Columbia, United States

Boca Raton Hospital

Boca Raton, Florida, United States

University of Florida

Gainesville, Florida, United States

Mayo Clinic

Jacksonville, Florida, United States

Lakeland Regional Cancer Center

Lakeland, Florida, United States

University of Miami

Miami, Florida, United States

USF Tampa General

Tampa, Florida, United States

MOFFITT

Tampa, Florida, United States

Illinois Cancer Specialists

Arlington Heights, Illinois, United States

Northwestern University

Chicago, Illinois, United States

Northshore University Health Systems

Evanston, Illinois, United States

Edward H. Kaplan, MD and Associates

Skokie, Illinois, United States

Indiana University Health Goshen Center for Cancer Care

Goshen, Indiana, United States

Indiana University

Indianapolis, Indiana, United States

Investigative Clinical Research of Indiana, LLC

Indianapolis, Indiana, United States

University of Iowa

Iowa City, Iowa, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

University of Louisville

Louisville, Kentucky, United States

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, United States

Ochsner Cancer Institute

New Orleans, Louisiana, United States

University of Maryland

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Lahey Clinic

Burlington, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

Beaumont Hospital

Royal Oak, Michigan, United States

Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Missouri

Columbia, Missouri, United States

Washington University

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

University of New Mexico

Albuquerque, New Mexico, United States

Mount Sinai Medical Center

New York, New York, United States

Columbia University

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest Baptist Health Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

University Hospitals Case Western

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

University of Oklahoma

Oklahoma City, Oklahoma, United States

Oregon Health and Science University

Portland, Oregon, United States

St. Luke's Hospital and Health Network

Bethlehem, Pennsylvania, United States

Penn State Hershey Cancer Institute

Hershey, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

University of Pittsburg Medical Center

Pittsburgh, Pennsylvania, United States

Roger Williams Medical Center

Providence, Rhode Island, United States

Greenville Health System

Greenville, South Carolina, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Ben Taub Hospital

Houston, Texas, United States

The Methodist Hospital

Houston, Texas, United States

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, United States

University of Texas Health Sciences

San Antonio, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

Lynchburg Hematology-Oncology Clinic, Inc.

Lynchburg, Virginia, United States

Virginia Commonwealth University

Richmond, Virginia, United States

University of Washington- Seattle Cancer Center Alliance

Seattle, Washington, United States

Vince Lombardi Cancer Clinic

Green Bay, Wisconsin, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

Hardacre JM, Mulcahy M, Small W, Talamonti M, Obel J, Krishnamurthi S, Rocha-Lima CS, Safran H, Lenz HJ, Chiorean EG. Addition of algenpantucel-L immunotherapy to standard adjuvant therapy for pancreatic cancer: a phase 2 study. J Gastrointest Surg. 2013 Jan;17(1):94-100; discussion p. 100-1. doi: 10.1007/s11605-012-2064-6. Epub 2012 Nov 15.

Reference Type: DERIVED

PMID: 23229886 (View on PubMed)

Other Identifiers

OBA# 0912-1013

Identifier Type: OTHER

Identifier Source: secondary_id

NLG0405

Identifier Type: -

Identifier Source: org_study_id