Clinical trial NCT01072981: Immunotherapy Study for Surgically Resected Pancreatic Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: Pancreatic Cancer
Vaccine Therapy
Lead sponsor: Lumos Pharma
Sponsor class: INDUSTRY
First posted: 2010-02-22
Enrollment: 722
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: The primary objective is to assess overall survival
timeFrame: Approximately 41 months and 48 months
Secondary outcomes:
measure: 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.
timeFrame: Approximately 41 months and 48 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: Sacramento
country: United States
facility: Sutter Institute for Medical Research
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Stamford
country: United States
facility: Stamford Hospital
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Boca Raton
country: United States
facility: Boca Raton Hospital
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: USF Tampa General
state: Florida
city: Tampa
country: United States
facility: MOFFITT
state: Florida
city: Arlington Heights
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Evanston
country: United States
facility: Northshore University Health Systems
state: Illinois
city: Skokie
country: United States
facility: Edward H. Kaplan, MD and Associates
state: Illinois
city: Goshen
country: United States
facility: Indiana University Health Goshen Center for Cancer Care
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: Investigative Clinical Research of Indiana, LLC
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Cancer Institute
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health Comprehensive Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Western
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Hospital and Health Network
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburg Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Roger Williams Medical Center
state: Rhode Island
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Ben Taub Hospital
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Sciences
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Lynchburg
country: United States
facility: Lynchburg Hematology-Oncology Clinic, Inc.
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington- Seattle Cancer Center Alliance
state: Washington
city: Green Bay
country: United States
facility: Vince Lombardi Cancer Clinic
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
References:
citation: 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.