Immunotherapy Study in Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer

Summary

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. One 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 substantially increase long term survival rates is reflected by the poor outcomes associated with this disease, specifically time to disease progression and overall survival.

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 effectively 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 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, as with the differences between organs from different species, the rejection is very rapid, highly destructive, and the immunity it generates is longlasting. 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, Algenpantucel-L immunotherapy contains human pancreatic cancer cells that contain a mouse gene that marks the cancer cells as foreign to patient's immune systems. The immune system therefore attacks these cancer cells just as they would attack any truly foreign tissue, destroying as much as it can. Additionally, the immune system is stimulated to identify differences (aside from the mouse gene) between these cancer cells and normal human tissue as foreign. This "education" of the immune system helps treat the patient because pancreatic cancer cells already present in a treated patient are believed to show some of the same differences from normal tissue as the modified pancreatic cancer cells in the product. Due to these similarities, the immune system, once "educated" by the Algenpantucel-L immunotherapy, identifies the patient's cancer as foreign and attacks.

The chemotherapy combination to be used in this study has been shown to improve survival in advanced pancreatic cancer and is being combined with an experimental pancreatic cancer immunotherapy that stimulates the immune system to recognize and attack the cancer. One goal of this study is to determine whether chemotherapy and immunotherapies can work cooperatively to increase anti-tumor effects to levels beyond what would be seen with either treatment alone.

In this experimental study, all patients are given a strong combination of anti-tumor chemotherapies while some patients are also given injections of an immunotherapy drug consisting of two types of pancreatic cancer cells that we have modified to make them more easily recognized and attacked by the immune system. We propose to test this new treatment protocol in patients with locally advanced pancreatic cancer to demonstrate that treatment with the immunotherapy increases the time until the tumor progresses or increases overall survival when given in combination with the current standard of care therapy for this disease.

Conditions

• Pancreatic Cancer
• Pancreatic Carcinoma Non-resectable
• Locally Advanced Malignant Neoplasm

Interventions

DRUG

FOLFIRINOX

FOLFIRINOX consisting of Oxaliplatin 85 mg/m\^2 IV over 2 hours; Irinotecan 180 mg/m\^2 IV over 90 minutes; Leucovorin 400 mg/m\^2 IV over 2 hours; Fluorouracil 2.4 g/m\^2 IV over 46 hours

BIOLOGICAL

Algenpantucel-L Immunotherapy

Algenpantucel-L Immunotherapy (HAPa) consisting of 300 Million HAPa cells given by intradermal injection

RADIATION

5-FU Chemoradiation

5-FU Chemoradiation consisting of 5-FU continuous IV infusion of 200-250 mg/m\^2/day given 5-7 days each week over 5.5 weeks concurrently with external beam radiation

DRUG

Gemcitabine

Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest.

DRUG

Capecitabine

Capecitabine consisting of 825 mg/m\^2 PO BID M-F concurrently with external beam radiation

DRUG

Nab-Paclitaxel

Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes

Sponsors & Collaborators

• NewLink Genetics Corporation

  lead INDUSTRY

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-05-31

Primary Completion

2016-07-29

Completion

2017-03-24

Countries

• United States

Study Locations