Immunotherapy Study for Surgically Resected Pancreatic Cancer

Sponsor

NewLink Genetics Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT01072981

Collaborator

(none)

722

Enrollment

Locations

Arms

Duration (Months)

9.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Biological: HyperAcute-Pancreas Immunotherapy Drug: Gemcitabine Radiation: 5FU Chemoradiation	Phase 3

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

Study Design

Study Type:

Interventional

Actual Enrollment :

722 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2010

Actual Primary Completion Date :

May 1, 2016

Actual Study Completion Date :

May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HyperAcute-Pancreas Immunotherapy + Standard of Care *Adjuvant Standard of Care Treatment (SOC) consisting of gemcitabine with or without 5FU chemoradiation + HyperAcute Immunotherapy	Biological: HyperAcute-Pancreas Immunotherapy Up to 18 immunizations of 300 million immunotherapy cells Other Names: HAPa-1 and HAPa-2 immunotherapy components Drug: Gemcitabine Gemcitabine 1000 mg/m2/day once a week for 3 weeks Other Names: Gemzar Radiation: 5FU Chemoradiation 5FU 200-250 mg/m2/day over 5 1/2 weeks with radiation. Other Names: Fluorouracil
Active Comparator: Standard of Care alone *Adjuvant Standard of Care Treatment (SOC) consisting of gemcitabine with or without 5FU chemoradiation Alone	Drug: Gemcitabine Gemcitabine 1000 mg/m2/day once a week for 3 weeks Other Names: Gemzar Radiation: 5FU Chemoradiation 5FU 200-250 mg/m2/day over 5 1/2 weeks with radiation. Other Names: Fluorouracil

Arm

Intervention/Treatment

Experimental: HyperAcute-Pancreas Immunotherapy + Standard of Care

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

Biological: HyperAcute-Pancreas Immunotherapy

Up to 18 immunizations of 300 million immunotherapy cells

Other Names:

HAPa-1 and HAPa-2 immunotherapy components

Drug: Gemcitabine

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

Other Names:

Gemzar

Radiation: 5FU Chemoradiation

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

Other Names:

Fluorouracil

Active Comparator: Standard of Care alone

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

Drug: Gemcitabine

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

Other Names:

Gemzar

Radiation: 5FU Chemoradiation

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

Other Names:

Fluorouracil

Outcome Measures

Primary Outcome Measures

The primary objective is to assess overall survival [Approximately 41 months and 48 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:
1. Marrow: white blood cells (WBC) ≥3000/mm3 and platelets ≥100,000/mm3.
1. Hepatic: serum total bilirubin ≤2 x ULN mg/dL, ALT (SGPT) and AST (SGOT) ≤3 x upper limit of normal (ULN).
1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35249
2	University of South Alabama	Mobile	Alabama	United States	36604
3	Arizona Cancer Center	Tucson	Arizona	United States	85724
4	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
5	City of Hope National Medical Center	Duarte	California	United States	91010
6	University of Southern California	Los Angeles	California	United States	90033
7	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
8	Stanford Cancer Center	Palo Alto	California	United States	94304
9	Sutter Institute for Medical Research	Sacramento	California	United States	95816
10	California Pacific Medical Center	San Francisco	California	United States	94115
11	University of Colorado	Aurora	Colorado	United States	80045
12	Stamford Hospital	Stamford	Connecticut	United States	06902
13	Georgetown University	Washington	District of Columbia	United States	20007
14	Boca Raton Hospital	Boca Raton	Florida	United States	33486
15	University of Florida	Gainesville	Florida	United States	32610
16	Mayo Clinic	Jacksonville	Florida	United States	32224
17	Lakeland Regional Cancer Center	Lakeland	Florida	United States	33805
18	University of Miami	Miami	Florida	United States	33136
19	USF Tampa General	Tampa	Florida	United States	33606
20	MOFFITT	Tampa	Florida	United States	33612
21	Illinois Cancer Specialists	Arlington Heights	Illinois	United States	60005
22	Northwestern University	Chicago	Illinois	United States	60611
23	Northshore University Health Systems	Evanston	Illinois	United States	60201
24	Edward H. Kaplan, MD and Associates	Skokie	Illinois	United States	60076
25	Indiana University Health Goshen Center for Cancer Care	Goshen	Indiana	United States	46526
26	Indiana University	Indianapolis	Indiana	United States	46202
27	Investigative Clinical Research of Indiana, LLC	Indianapolis	Indiana	United States	46260
28	University of Iowa	Iowa City	Iowa	United States	52242
29	University of Kansas Cancer Center	Westwood	Kansas	United States	66205
30	University of Louisville	Louisville	Kentucky	United States	40202
31	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
32	Ochsner Cancer Institute	New Orleans	Louisiana	United States	70121
33	University of Maryland	Baltimore	Maryland	United States	21201
34	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
35	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
36	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
37	Lahey Clinic	Burlington	Massachusetts	United States	01805
38	University of Michigan	Ann Arbor	Michigan	United States	48109
39	Henry Ford Hospital	Detroit	Michigan	United States	48202
40	Beaumont Hospital	Royal Oak	Michigan	United States	48073
41	Virginia Piper Cancer Institute	Minneapolis	Minnesota	United States	55409
42	Mayo Clinic	Rochester	Minnesota	United States	55905
43	University of Missouri	Columbia	Missouri	United States	65203
44	Washington University	Saint Louis	Missouri	United States	63110
45	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
46	University of New Mexico	Albuquerque	New Mexico	United States	87106
47	Mount Sinai Medical Center	New York	New York	United States	10029
48	Columbia University	New York	New York	United States	10032
49	Duke University Medical Center	Durham	North Carolina	United States	27710
50	Wake Forest Baptist Health Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157
51	University of Cincinnati	Cincinnati	Ohio	United States	45267
52	University Hospitals Case Western	Cleveland	Ohio	United States	44106
53	Ohio State University	Columbus	Ohio	United States	43221
54	University of Oklahoma	Oklahoma City	Oklahoma	United States	73104
55	Oregon Health and Science University	Portland	Oregon	United States	97239
56	St. Luke's Hospital and Health Network	Bethlehem	Pennsylvania	United States	18015
57	Penn State Hershey Cancer Institute	Hershey	Pennsylvania	United States	17033
58	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
59	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
60	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
61	University of Pittsburg Medical Center	Pittsburgh	Pennsylvania	United States	15232
62	Roger Williams Medical Center	Providence	Rhode Island	United States	02908
63	Greenville Health System	Greenville	South Carolina	United States	29615
64	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
65	Baylor College of Medicine	Houston	Texas	United States	77030
66	Ben Taub Hospital	Houston	Texas	United States	77030
67	The Methodist Hospital	Houston	Texas	United States	77030
68	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410
69	University of Texas Health Sciences	San Antonio	Texas	United States	78229
70	University of Virginia	Charlottesville	Virginia	United States	22908
71	Lynchburg Hematology-Oncology Clinic, Inc.	Lynchburg	Virginia	United States	24501
72	Virginia Commonwealth University	Richmond	Virginia	United States	23298
73	University of Washington- Seattle Cancer Center Alliance	Seattle	Washington	United States	98109
74	Vince Lombardi Cancer Clinic	Green Bay	Wisconsin	United States	54311
75	University of Wisconsin	Madison	Wisconsin	United States	53705