Immunotherapy and SBRT Study in Borderline Resectable Pancreatic Cancer
|ClinicalTrials.gov Identifier: NCT02405585|
Recruitment Status : Terminated
First Posted : April 1, 2015
Last Update Posted : February 26, 2019
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, 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.
Historically, external beam radiation has been part of the treatment of pancreatic cancer, both before and after surgical resection. Recent breakthroughs in technology now allow for more intensive doses of radiation to be delivered to the body with greater precision. These newer, more precise radiation treatments, called stereotactic body radiation, deliver more intensive radiation to a locally advanced tumor and are now being employed in the treatment of pancreatic cancer. Stereotactic body radiation may increase the chances that surgery will successfully remove a pancreatic cancer.
In this experimental study, all patients will be given a strong combination of antitumor chemotherapy while receiving injections of an immunotherapy drug consisting of two types of pancreatic cancer cells that have been modified to make them more easily recognized and attacked by the immune system. The investigators propose to test this new treatment paradigm along with stereotactic body radiation in patients with borderline resectable pancreatic cancer to demonstrate that treatment with this combination of therapies increases the time until the tumor progresses as well as overall survival.
|Condition or disease||Intervention/treatment||Phase|
|Pancreatic Cancer Pancreatic Carcinoma Non-resectable||Drug: mFOLFIRINOX Biological: Algenpantucel-L Immunotherapy Radiation: SBRT Drug: Gemcitabine||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Exploratory Phase 2 Study of Neoadjuvant Chemotherapy Followed by Stereotactic Body Radiation Therapy (SBRT) With Algenpantucel-L (HyperAcute®-Pancreas) Immunotherapy in Subjects With Borderline Resectable Pancreatic Cancer|
|Study Start Date :||April 2015|
|Actual Primary Completion Date :||June 30, 2016|
|Actual Study Completion Date :||July 30, 2016|
Experimental: mFOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy
SOC mFOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy
Day 93-100 Disease evaluated: Progressive disease = salvage therapy off study. Day 93-100 Disease evaluated: Stable disease or better = SBRT + HAPa on days 1 and 15 of radiotherapy Post SBRT: surgery + adjuvant SOC Gemcitabine + HAPa given 1 and 15 for 6 cycles.
Post adjuvant therapy: 6 monthly immunizations with HAPa
mFOLFIRINOX 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 - given on days 15, 29, 43, 57, 71 and 85
Biological: Algenpantucel-L Immunotherapy
HAPa1 and HAPa2 immunotherapy components Algenpantucel-L Immunotherapy (HAPa) consisting of 300 Million HAPa cells given by intradermal injection for up to 28 doses total.
Subjects that have at least stable disease at evaluation (day 93-100) are eligible to receive SBRT radiation given at 1.8 Gy per fraction for 28 fractions for a total dose of 50.4 Gy.
Gemcitabine 1000 mg/m^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest.
Given as adjuvant treatment (days 1, 8 and 15) with 1 week rest for 6 cycles after surgical resection.
Other Name: Gemzar
- Progression Free Survival [ Time Frame: 18 months (assuming enrollment period of 1 year) ]The primary objective of this study is to assess progression free survival after treatment with a regimen of mFOLFIRINOX with algenpantucel-L immunotherapy followed by SBRT in subjects who have borderline resectable pancreatic cancer.
- Overall Survival [ Time Frame: 30 months (assuming enrollment period of 1 year) ]A secondary objective of this study is to assess overall survival (OS) in pancreatic cancer patients with borderline resectable pancreatic cancer who will receive a regimen of mFOLFIRINOX with algenpantucel-L Immunotherapy followed by SBRT.
- Frequency and grade of adverse events of FOLFIRINOX in combination with algenpantucel-L Immunotherapy [ Time Frame: 18 months (assuming enrollment period of 1 year) ]A secondary objective of this study is to assess the safety (frequency and grade of adverse events) of administration of algenpantucel-L Immunotherapy given in combination with a standard of care regimen of chemotherapy mFOLFIRINOX followed by SBRT
- Immune Response [ Time Frame: 18 months (assuming enrollment period of 1 year) ]A secondary objective of this study is to assess the immunologic responses of subjects with pancreatic cancer undergoing antitumor immunization with algenpantucel-L Immunotherapy as measured by anti-alpha Gal antibodies, and-tumor antibodies, and total IgE.
- Tumor Response [ Time Frame: 18 months (assuming enrollment period of 1 year) ]A secondary objective of this study is to assess the tumor response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Immune Response Criteria (irRC).
- Resection Rate [ Time Frame: 18 months (assuming enrollment period of 1 year) ]A secondary objective of this study is to assess the R0 resection rate following neoadjuvant chemotherapy, immunotherapy and SBRT.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02405585
|United States, Kentucky|
|University of Louisville|
|Louisville, Kentucky, United States, 40292|
|United States, Massachusetts|
|Burlington, Massachusetts, United States|
|United States, New Mexico|
|New Mexico Cancer Care Alliance|
|Albuquerque, New Mexico, United States, 87106|
|United States, Washington|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109|