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A Phase III Study of FOLFIRINOX With or Without HyperAcute®-Pancreas (Algenpantucel-L) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer

Phase 3
18 Years
Open (Enrolling)
Pancreatic Cancer, Pancreatic Carcinoma Non-resectable, Locally Advanced Malignant Neoplasm

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Trial Information

A Phase III Study of FOLFIRINOX With or Without HyperAcute®-Pancreas (Algenpantucel-L) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer

This protocol attempts pancreatic cancer therapy using a naturally occurring barrier to
xenotransplantation in humans to increase the efficacy of immunizing patients against their
pancreatic cancer. In this protocol, the transfer of the murine α(1,3) galactosyltransferase
[α(1,3)GT] gene to immunotherapy component cells results in the cell surface expression of
α(1,3)galactosyl-epitopes (αgal) epitopes on membrane glycoproteins and glycolipids. These
epitopes are the major target of the hyperacute rejection response. This response occurs
when organs are transplanted from lower animal donor species into primates and results in
rapid destruction of transplanted tissue and an augmented response against transplant
antigens, including antigens not related to the αgal epitopes. Human hosts have pre-existing
anti-α-gal antibodies that are thought to result from chronic immunological stimulation due
to exposure to α-gal epitopes that are naturally expressed on normal gut flora and these
antibodies may comprise up to 1% of serum immunoglobulin G (IgG). Opsonization and lysis of
the immunotherapy component cells mediated by this antibody is believed to increase the
efficiency of antigen processing by targeting vaccine components to antigen presenting cells
via the Fcγ receptor.

Inclusion Criteria:

- A histological diagnosis of adenocarcinoma of the pancreas confirmed by pathology.

- Patients must have borderline resectable or locally advanced unresectable pancreatic
cancer with no metastatic spread as determined by a baseline diagnostic CT scan with
intravenous contrast (or MRI). CT should be performed according to a defined pancreas
protocol such as triphasic cross-sectional imaging with thin slices. Optimal
multi-phase technique including a non-contrast phase plus arterial, pancreatic
parenchymal and portal venous phase of contrast enhancement with thin cuts (3mm)
throughout the abdomen is preferred. Studies must be evaluated by a radiologist
and/or surgeon and deemed borderline resectable or locally advanced unresectable as
defined per the NCCN Practice Guidelines in Oncology V2.2012, as:

- Borderline resectable- Tumors considered borderline resectable are defined as

1. No distant metastases

2. Venous involvement of the SMV/portal vein demonstrating tumor abutment with
impingement and narrowing of the lumen, encasement of the SMV/portal vein but
without encasement of the nearby arteries, or short-segment venous occlusion
resulting from either tumor thrombus or encasement but with suitable vessel
proximal and distal to the area of vessel involvement, allowing for safe
resection and reconstruction

3. Gastroduodenal artery encasement up to the hepatic artery with either short
segment encasement or direct abutment of the hepatic artery without extension to
the celiac axis.

4. Tumor abutment of the SMA not to exceed greater than 180 degrees of the
circumference of the vessel wall.

- Tumors considered to be unresectable due to local advancement include an absence of
distant metastases as well as:

1. Head: Greater than 180 degrees SMA encasement or any celiac abutment or
unreconstructible SMV/portal occlusion or aortic invasion or encasement.

2. Body: Greater than 180 degrees SMA or celiac encasement or unreconstructible
SMV/portal occlusion or aortic invasion.

3. Tail: SMA or celiac encasement greater than 180 degrees.

4. Nodal status: Involvement of lymph nodes beyond the field of resection should be
considered unresectable due to distant spread and therefore not eligible for
this protocol.

- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.

- Serum albumin ≥ 2.0 gm/dL.

- Expected survival ≥ 6 months.

- Adequate organ function including:

1. Marrow: WBC ≥3000/mm^3 and platelets ≥100,000/mm^3.

2. Hepatic: serum total bilirubin ≤ 2 mg/dL, ALT (SGPT) and AST (SGOT) ≤3 x upper
limit of normal (ULN) at time of enrollment. If a patient has elevated liver
function tests at the time of initial presentation or develops them during
work-up and they are the result of a mechanical obstruction of biliary drainage
by tumor compression or invasion, a biliary drain may be placed as described in
NCCN Practice Guidelines in Oncology V2.2012. If drainage allows for the liver
function tests to come within inclusion criteria, the patient may be enrolled.

3. Renal: serum creatinine (sCr) ≤2.0 x ULN, or creatinine clearance (Ccr) ≥30

- 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.

- 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 per the
FOLFIRINOX regimen. Subjects receiving inhaled or topical corticosteroids are
eligible. Subjects who require chronic systemic corticosteroids after beginning
treatment, will be removed from study.

- Significant or uncontrolled congestive heart failure (CHF), myocardial infarction or
significant ventricular arrhythmias within the last six months.

- Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring
systemic therapy.

- Autoimmune disease (e.g., systemic lupus erythematosis (SLE), rheumatoid arthritis
(RA), etc.). Patients with a remote history of asthma or mild active asthma are

- Other serious medical conditions that may be expected to limit life expectancy to
less than 2 years (e.g., active 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 history of allergy or hypersensitivity to any of the study drugs or any of
their excipients.

- Pregnant or nursing women due to the unknown effects of immunization on the
developing fetus or newborn infant. (For patients with child bearing potential, a
βHCG must be completed within 14 days of first treatment).

- Known HIV positive.

- Prior treatment with chemotherapy or radiation for pancreatic cancer or prior
treatment with radiation for other diagnoses to expected pancreatic cancer treatment

- Current grade II or higher peripheral neuropathy.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Survival

Outcome Description:

The primary objective of this study is to assess overall survival (OS) in pancreatic cancer patients with borderline resectable or locally advanced unresectable pancreatic cancer who will receive a regiment of FOLFIRINOX with or without HyperAcute®-Pancreas Immunotherapy.

Outcome Time Frame:

13.5 months (assuming enrollment period of 1-2 years)

Safety Issue:


Principal Investigator

Nicholas N Vahanian, MD

Investigator Role:

Study Director

Investigator Affiliation:

NewLink Genetics Corporation


United States: Food and Drug Administration

Study ID:




Start Date:

April 2013

Completion Date:

June 2017

Related Keywords:

  • Pancreatic Cancer
  • Pancreatic Carcinoma Non-resectable
  • Locally Advanced Malignant Neoplasm
  • Pancreatic Cancer
  • Immunotherapy
  • Vaccine Therapy
  • Neoplasms
  • Carcinoma
  • Pancreatic Neoplasms



Virginia Piper Cancer Institute Minneapolis, Minnesota  55407
University of Oklahoma Oklahoma City, Oklahoma  73190
California Pacific Medical Center San Francisco, California  94115
University of Miami Miami, Florida  33136
Oregon Health and Science University Portland, Oregon  97201