Immunotherapy Study for Surgically Resected Pancreatic Cancer

Pancreatic Cancer Clinical Trial

Official title:

A Phase III Study of Chemotherapy and Chemoradiotherapy With or Without Algenpantucel-L (HyperAcute®-Pancreas) Immunotherapy in Subjects With Surgically Resected Pancreatic Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01072981
• Other study ID #: NLG0405
• Secondary ID: OBA# 0912-1013
• Status: Completed
• Phase: Phase 3
• Start date: April 2010
• Est. completion date: May 2016

Study information

• Verified date: May 2020
• Source: Lumos Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 722
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ßHCG must be completed within 14 days of first vaccination).

• Known HIV positive.

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Biological:
• HyperAcute-Pancreas Immunotherapy
Up to 18 immunizations of 300 million immunotherapy cells

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

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

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	University of Michigan	Ann Arbor	Michigan
United States	Illinois Cancer Specialists	Arlington Heights	Illinois
United States	University of Colorado	Aurora	Colorado
United States	University of Maryland	Baltimore	Maryland
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	St. Luke's Hospital and Health Network	Bethlehem	Pennsylvania
United States	University of Alabama	Birmingham	Alabama
United States	Boca Raton Hospital	Boca Raton	Florida
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Lahey Clinic	Burlington	Massachusetts
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	University Hospitals Case Western	Cleveland	Ohio
United States	University of Missouri	Columbia	Missouri
United States	Ohio State University	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Northshore University Health Systems	Evanston	Illinois
United States	University of Florida	Gainesville	Florida
United States	Indiana University Health Goshen Center for Cancer Care	Goshen	Indiana
United States	Vince Lombardi Cancer Clinic	Green Bay	Wisconsin
United States	Greenville Health System	Greenville	South Carolina
United States	Penn State Hershey Cancer Institute	Hershey	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	Ben Taub Hospital	Houston	Texas
United States	The Methodist Hospital	Houston	Texas
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	Mayo Clinic	Jacksonville	Florida
United States	Lakeland Regional Cancer Center	Lakeland	Florida
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Lynchburg Hematology-Oncology Clinic, Inc.	Lynchburg	Virginia
United States	University of Wisconsin	Madison	Wisconsin
United States	University of Miami	Miami	Florida
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	University of South Alabama	Mobile	Alabama
United States	Ochsner Cancer Institute	New Orleans	Louisiana
United States	Columbia University	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Stanford Cancer Center	Palo Alto	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburg Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Roger Williams Medical Center	Providence	Rhode Island
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Beaumont Hospital	Royal Oak	Michigan
United States	Sutter Institute for Medical Research	Sacramento	California
United States	Washington University	Saint Louis	Missouri
United States	University of Texas Health Sciences	San Antonio	Texas
United States	California Pacific Medical Center	San Francisco	California
United States	University of Washington- Seattle Cancer Center Alliance	Seattle	Washington
United States	Edward H. Kaplan, MD and Associates	Skokie	Illinois
United States	Stamford Hospital	Stamford	Connecticut
United States	MOFFITT	Tampa	Florida
United States	USF Tampa General	Tampa	Florida
United States	Arizona Cancer Center	Tucson	Arizona
United States	Georgetown University	Washington	District of Columbia
United States	University of Kansas Cancer Center	Westwood	Kansas
United States	Wake Forest Baptist Health Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
NewLink Genetics Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary objective is to assess overall survival		Approximately 41 months and 48 months
Secondary	The secondary objective is to assess disease free survival and to conduct correlative scientific studies of subject samples to determine the mechanism of any observed anti-tumor effect.		Approximately 41 months and 48 months