Pancreatic Cancer Clinical Trial
— PILLAROfficial title:
A Phase III Study of Chemotherapy With or Without Algenpantucel-L (HyperAcute®-Pancreas) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer
Verified date | May 2020 |
Source | Lumos Pharma |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Terminated |
Enrollment | 302 |
Est. completion date | March 24, 2017 |
Est. primary completion date | July 29, 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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 follows: 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 = 1.5 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 mL/min. - 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 or gemcitabine/nab-paclitaxel 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 eligible. - 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 ßHCG 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 fields. - Current grade II or higher peripheral neuropathy. |
Country | Name | City | State |
---|---|---|---|
United States | Illinois Cancer Specialists | Arlington Heights | Illinois |
United States | Boca Raton Regional Hospital | Boca Raton | Florida |
United States | University of Virginia | Charlottesville | Virginia |
United States | The Ohio State University | Columbus | Ohio |
United States | University of Texas Southwestern Medical Center | Dallas | Texas |
United States | University of Florida | Gainesville | Florida |
United States | Indiana University Health Goshen Center for Cancer Care | Goshen | Indiana |
United States | Vince Lombardi Cancer Center | Green Bay | Wisconsin |
United States | Baylor College of Medicine | Houston | Texas |
United States | Indiana University | Indianapolis | Indiana |
United States | University of Tennessee Medical Center | Knoxville | Tennessee |
United States | Cedars-Sinai Medical Center | Los Angeles | California |
United States | University of Louisville | Louisville | Kentucky |
United States | University of Wisconsin | Madison | Wisconsin |
United States | University of Miami | Miami | Florida |
United States | Virginia Piper Cancer Institute | Minneapolis | Minnesota |
United States | Jersey Shore University Medical Center | Neptune | New Jersey |
United States | Mount Sinai Medical Center | New York | New York |
United States | University of Oklahoma | Oklahoma City | Oklahoma |
United States | Thomas Jefferson University | Philadelphia | Pennsylvania |
United States | Oregon Health and Science University | Portland | Oregon |
United States | Renown Regional Medical Center | Reno | Nevada |
United States | Beaumont CCOP | Royal Oak | Michigan |
United States | Sutter Institute for Medical Research | Sacramento | California |
United States | California Pacific Medical Center | San Francisco | California |
United States | University of Washington - Seattle Cancer Center Alliance | Seattle | Washington |
United States | Stamford Hospital | Stamford | Connecticut |
United States | H. Lee Moffitt Cancer Center | Tampa | Florida |
United States | USF Tampa General | Tampa | Florida |
United States | Arizona Cancer Center | Tucson | Arizona |
United States | University of Kansas Cancer Center | Westwood | Kansas |
United States | Wake Forest Baptist Health | Winston-Salem | North Carolina |
Lead Sponsor | Collaborator |
---|---|
NewLink Genetics Corporation |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Overall Survival | 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 regimen of FOLFIRINOX or gemcitabine/nab-paclitaxel with or without algenpantucel-L Immunotherapy. | 13.5 months (assuming enrollment period of 1-2 years) | |
Secondary | Progression Free Survival | A secondary objective of this study is to assess progression free survival after treatment with a regimen of FOLFIRINOX or gemcitabine/nab-paclitaxel with or without algenpantucel-L immunotherapy in subjects who have borderline resectable or locally advanced pancreatic cancer. | 13.5 months (assuming enrollment period of 1-2 years) | |
Secondary | Frequency and grade of adverse events of FOLFIRINOX or gemcitabine/nab-paclitaxel in combination with algenpantucel-L Immunotherapy versus FOLFIRINOX or gemcitabine/nab-paclitaxel alone | 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 (FOLFIRINOX or gemcitabine/nab-paclitaxel, to be referred to as standard of care, or SOC). | 13.5 months (assuming enrollment period of 1-2 years) | |
Secondary | Immune Response | 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 correlative laboratory studies. | 13.5 months (assuming enrollment period of 1-2 years) |
Status | Clinical Trial | Phase | |
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