Pancreatic CancerPhase 3PILLARNCT01836432
Immunotherapy Study in Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer
A Phase 3 study testing FOLFIRINOX, Algenpantucel-L Immunotherapy and 5-FU Chemoradiation in people with Pancreatic Cancer and Pancreatic Carcinoma Non-resectable, run by NewLink Genetics Corporation at 32 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer, Pancreatic Carcinoma Non-resectable, Locally Advanced Malignant Neoplasm
- What is being tested?
- FOLFIRINOX, Algenpantucel-L Immunotherapy and 5-FU Chemoradiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 302 participants
- Where
- 32 sitesUnited States
- Study dates
- May 2013to 24 Mar 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- No distant metastases
- 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
- 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.
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- 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:
- Head: Greater than 180 degrees SMA encasement or any celiac abutment or unreconstructible SMV/portal occlusion or aortic invasion or encasement.
- Body: Greater than 180 degrees SMA or celiac encasement or unreconstructible SMV/portal occlusion or aortic invasion.
- Tail: SMA or celiac encasement greater than 180 degrees.
- 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:
- Marrow: WBC ≥3000/mm^3 and platelets ≥100,000/mm^3.
- 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.
- 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.
Who cannot join
- 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.
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- 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 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 fields.
- Current grade II or higher peripheral neuropathy.
Trial locations and contacts
32 sites in 1 country.
32 sites in 1 country
United States32 sites
Illinois Cancer Specialists
Arlington Heights, Illinois, 60005
Boca Raton Regional Hospital
Boca Raton, Florida, 33486
University of Virginia
Charlottesville, Virginia, 22904
The Ohio State University
Columbus, Ohio, 43210
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Florida
Gainesville, Florida, 32610
Indiana University Health Goshen Center for Cancer Care
Goshen, Indiana, 46526
Vince Lombardi Cancer Center
Green Bay, Wisconsin, 54311
Baylor College of Medicine
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of Tennessee Medical Center
Knoxville, Tennessee, 37920
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of Louisville
Louisville, Kentucky, 40292
University of Wisconsin
Madison, Wisconsin, 53792
University of Miami
Miami, Florida, 33136
Virginia Piper Cancer Institute
Minneapolis, Minnesota, 55407-3799
Jersey Shore University Medical Center
Neptune City, New Jersey, 07753
Mount Sinai Medical Center
New York, New York, 10029
University of Oklahoma
Oklahoma City, Oklahoma, 73104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Oregon Health and Science University
Portland, Oregon, 97239
Renown Regional Medical Center
Reno, Nevada, 89502
Beaumont CCOP
Royal Oak, Michigan, 48073
Sutter Institute for Medical Research
Sacramento, California, 95816
California Pacific Medical Center
San Francisco, California, 94115
University of Washington - Seattle Cancer Center Alliance
Seattle, Washington, 98109
Stamford Hospital
Stamford, Connecticut, 06902
USF Tampa General
Tampa, Florida, 33606
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
Arizona Cancer Center
Tucson, Arizona, 85719
University of Kansas Cancer Center
Westwood, Kansas, 66205
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
About this study
Official 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
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.
Read more
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.
Read the detailed description
This protocol attempts to treat 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.
- Conditions
- Pancreatic Cancer, Pancreatic Carcinoma Non-resectable, Locally Advanced Malignant Neoplasm
- Being tested
- FOLFIRINOX, Algenpantucel-L Immunotherapy, 5-FU Chemoradiation, Gemcitabine, Capecitabine
- Keywords
- Pancreatic Cancer, Immunotherapy, Vaccine Therapy
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFIRINOXDrug
Also called Oxaliplatin, Eloxatin®, Irinotecan, Camptosar®
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
Algenpantucel-L ImmunotherapyBiological
Also called HyperAcute®-Pancreas, HAPa
Algenpantucel-L Immunotherapy (HAPa) consisting of 300 Million HAPa cells given by intradermal injection
5-FU ChemoradiationRadiation
Also called Fluorouracil, 5-Fluorouracil, 5-FU
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
GemcitabineDrug
Also called Gemzar
Gemcitabine 1000 mg/m^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest.
CapecitabineDrug
Also called Xeloda
Capecitabine consisting of 825 mg/m^2 PO BID M-F concurrently with external beam radiation
Nab-PaclitaxelDrug
Also called Abraxane, Paclitaxel
Nab-Paclitaxel 125 mg/m^2 given intravenously over 30-40 minutes
| Study group | Role | What they receive |
|---|---|---|
| FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy | Experimental | Arm 1A: SOC FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy
Day 71-80 Disease evaluated: New distant disease = salvage regimen Gem/Nab-Paclitaxel (6 cycles) + HAPa given days 8 and 22 for up to 18 doses total.
Day 71-80 Disease evaluated: No distant disease = 5-FU or capecitabine plus Radiation+ HAPa on days 1 and 15 of Chemoradiotherapy.
Post-Chemoradiation Disease evaluation: surgically resectable = surgery + adjuvant SOC Gemcitabine + HAPa given 1 and 15 for up to 18 doses total.
Post-Chemoradiation Disease evaluation: not eligible for surgical resection (Stable) = continue FOLFIRINOX bi-weekly + HAPa bi-weekly 7 days offset from FOLFIRINOX up to18 doses of algenpantucel-L Immunotherapy.
Post-Chemoradiation Disease evaluation: non-eligible for surgical resection (Progression) = salvage Gem/Nab-Paclitaxel (6 cycles) + HAPa given days 8 and 22 for up to 18 doses total. Receives: Drug: FOLFIRINOX; Biological: Algenpantucel-L Immunotherapy; Radiation: 5-FU Chemoradiation; Drug: Gemcitabine; Drug: Capecitabine; Drug: Nab-Paclitaxel |
| FOLFIRINOX (SOC) ALONE | Active comparator | Arm 2A: FOLFIRINOX (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 days 1, 15, 29, 43 \& 57
Day 71-80 Disease eval: New disease = salvage Gem/Nab-Paclitaxel: nab-paclitaxel 125mg/m^2 IV over 30-40 minutes followed by gemcitabine 1000 mg/m^2 IV over 30-60 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest
Day 71-80 Disease eval: No disease = 5-FU or capecitabine plus Radiation (5-FU continuous IV infusion of 200-250 mg/m^2/day given 5-7 days each week over 5.5 weeks or Capecitabine 825 mg/m^2 PO BID M-F) concurrently with external beam radiation given at 1.8 Gy per fraction for 28 fractions total dose of 50.4 Gy
Post-XRT Disease eval: surgically resectable = surgery + adjuvant SOC Gemcitabine
Ineligible for surgical resection \& stable disease = continue FOLFIRINOX
Ineligible for surgical resection \& progressive disease = salvage Gem/Nab-Paclitaxel Receives: Drug: FOLFIRINOX; Radiation: 5-FU Chemoradiation; Drug: Gemcitabine; Drug: Capecitabine; Drug: Nab-Paclitaxel |
| Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy | Experimental | Arm 1B: Gemcitabine/Nab-Paclitaxel + Algenpantucel-L (HAPa) Immunotherapy
Day 71-80 Disease evaluated: New distant disease = salvage regimen FOLFIRINOX + HAPa given every 14 days (alternate weeks of FOLFIRINOX) for up to 18 doses total.
Day 71-80 Disease evaluated: No distant disease = 5-FU or capecitabine plus Radiation + HAPa on days 1 and 15 of Chemoradiotherapy.
Post-Chemoradiation Disease evaluation: surgically resectable = surgery + adjuvant SOC Gemcitabine + HAPa given days 1 and 15 for up to 18 doses total.
Post-Chemoradiation Disease evaluation: not eligible for surgical resection (Stable) = continue Gem/Nab-Paclitaxel + HAPa given on days 8 and 22 for up to18 doses of algenpantucel-L Immunotherapy.
Post-Chemoradiation Disease evaluation: non-eligible for surgical resection (Progression) = salvage FOLFIRINOX + HAPa given every 14 days (alternate weeks of FOLFIRINOX) for up to 18 doses total. Receives: Drug: FOLFIRINOX; Biological: Algenpantucel-L Immunotherapy; Radiation: 5-FU Chemoradiation; Drug: Gemcitabine; Drug: Capecitabine; Drug: Nab-Paclitaxel |
| Gemcitabine/Nab-Paclitaxel (SOC) Alone | Active comparator | Arm 2B: Gemcitabine/Nab-Paclitaxel (SOC) Alone
SOC Gem/Nab-Paclitaxel: nab-paclitaxel 125mg/m^2 IV over 30-40 minutes followed by gemcitabine 1000 mg/m^2 IV over 30-60 minutes for 3 weeks with 1 week rest. Given on days 1, 8, 15, 29, 36, 43, 57, 64 and 71
Day 71-80 Disease evaluated: New distant disease = salvage FOLFIRINOX given every 14 days
Day 71-80 Disease evaluation: No disease = 5-FU or capecitabine plus Radiation (5-FU continuous IV infusion of 200-250 mg/m^2/day given 5-7 days each week over 5.5 weeks or Capecitabine 825 mg/m^2 PO BID M-F) concurrently with external beam radiation given at 1.8 Gy per fraction for 28 fractions total dose of 50.4 Gy
Post-XRT Disease eval: surgically resectable = surgery + adjuvant SOC Gemcitabine
Ineligible for surgical resection \& stable disease = continue gem/nab-paclitaxel given for 3 weeks (days 1, 8 and 15) with 1 week rest
Ineligible for surgical resection \& progressive disease = salvage FOLFIRINOX given every 14 days Receives: Drug: FOLFIRINOX; Radiation: 5-FU Chemoradiation; Drug: Gemcitabine; Drug: Capecitabine; Drug: Nab-Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 13.5 months (assuming enrollment period of 1-2 years)
Secondary outcomes (3)
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.
Measured: 13.5 months (assuming enrollment period of 1-2 years)
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).
Measured: 13.5 months (assuming enrollment period of 1-2 years)
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.
Measured: 13.5 months (assuming enrollment period of 1-2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2013 (estimated)
- Study startMay 2013
- Primary completion29 Jul 2016
- Study completion24 Mar 2017
Why it stopped: Company decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 302 participants (actual)
Sponsor and investigators
- Lead sponsor
- NewLink Genetics Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01836432
- Sponsor's protocol ID
- NLG0505
- Other IDs
- 1210-1195
- Acronym
- PILLAR
- Status last verified
- May 2020
- First submitted
- 17 Apr 2013
- Last updated
- 28 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hewitt DB, Nissen N, Hatoum H, Musher B, Seng J, Coveler AL, Al-Rajabi R, Yeo CJ, Leiby B, Banks J, Balducci L, Vaccaro G, LoConte N, George TJ, Brenner W, Elquza E, Vahanian N, Rossi G, Kennedy E, Link C, Lavu H. A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer. Ann Surg. 2022 Jan 1;275(1):45-53. doi: 10.1097/SLA.0000000000004669.
PubMed 33630475
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01836432
- Acronym / sponsor ID
- PILLAR / NLG0505
- Conditions
- Pancreatic Cancer, Pancreatic Carcinoma Non-resectable, Locally Advanced Malignant Neoplasm
- Keywords
- Pancreatic Cancer, Immunotherapy, Vaccine Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company decision
- Enrolment
- 302 participants (actual)
- Lead sponsor
- NewLink Genetics CorporationIndustry (pharma, biotech, devices)
- Study start
- May 2013
- Primary completion
- 29 Jul 2016 (actual)
- Study completion
- 24 Mar 2017 (actual)
- First posted
- 19 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This protocol attempts to treat 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy | Experimental | Drug: FOLFIRINOX, Biological: Algenpantucel-L Immunotherapy, Radiation: 5-FU Chemoradiation, Drug: Gemcitabine, Drug: Capecitabine, Drug: Nab-PaclitaxelArm 1A: SOC FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy Day 71-80 Disease evaluated: New distant disease = salvage regimen Gem/Nab-Paclitaxel (6 cycles) + HAPa given days 8 and 22 for up to 18 doses total. Day 71-80 Disease evaluated: No distant disease = 5-FU or capecitabine plus Radiation+ HAPa on days 1 and 15 of Chemoradiotherapy. Post-Chemoradiation Disease evaluation: surgically resectable = surgery + adjuvant SOC Gemcitabine + HAPa given 1 and 15 for up to 18 doses total. Post-Chemoradiation Disease evaluation: not eligible for surgical resection (Stable) = continue FOLFIRINOX bi-weekly + HAPa bi-weekly 7 days offset from FOLFIRINOX up to18 doses of algenpantucel-L Immunotherapy. Post-Chemoradiation Disease evaluation: non-eligible for surgical resection (Progression) = salvage Gem/Nab-Paclitaxel (6 cycles) + HAPa given days 8 and 22 for up to 18 doses total. |
| FOLFIRINOX (SOC) ALONE | Active comparator | Drug: FOLFIRINOX, Radiation: 5-FU Chemoradiation, Drug: Gemcitabine, Drug: Capecitabine, Drug: Nab-PaclitaxelArm 2A: FOLFIRINOX (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 days 1, 15, 29, 43 \& 57 Day 71-80 Disease eval: New disease = salvage Gem/Nab-Paclitaxel: nab-paclitaxel 125mg/m^2 IV over 30-40 minutes followed by gemcitabine 1000 mg/m^2 IV over 30-60 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest Day 71-80 Disease eval: No disease = 5-FU or capecitabine plus Radiation (5-FU continuous IV infusion of 200-250 mg/m^2/day given 5-7 days each week over 5.5 weeks or Capecitabine 825 mg/m^2 PO BID M-F) concurrently with external beam radiation given at 1.8 Gy per fraction for 28 fractions total dose of 50.4 Gy Post-XRT Disease eval: surgically resectable = surgery + adjuvant SOC Gemcitabine Ineligible for surgical resection \& stable disease = continue FOLFIRINOX Ineligible for surgical resection \& progressive disease = salvage Gem/Nab-Paclitaxel |
| Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy | Experimental | Drug: FOLFIRINOX, Biological: Algenpantucel-L Immunotherapy, Radiation: 5-FU Chemoradiation, Drug: Gemcitabine, Drug: Capecitabine, Drug: Nab-PaclitaxelArm 1B: Gemcitabine/Nab-Paclitaxel + Algenpantucel-L (HAPa) Immunotherapy Day 71-80 Disease evaluated: New distant disease = salvage regimen FOLFIRINOX + HAPa given every 14 days (alternate weeks of FOLFIRINOX) for up to 18 doses total. Day 71-80 Disease evaluated: No distant disease = 5-FU or capecitabine plus Radiation + HAPa on days 1 and 15 of Chemoradiotherapy. Post-Chemoradiation Disease evaluation: surgically resectable = surgery + adjuvant SOC Gemcitabine + HAPa given days 1 and 15 for up to 18 doses total. Post-Chemoradiation Disease evaluation: not eligible for surgical resection (Stable) = continue Gem/Nab-Paclitaxel + HAPa given on days 8 and 22 for up to18 doses of algenpantucel-L Immunotherapy. Post-Chemoradiation Disease evaluation: non-eligible for surgical resection (Progression) = salvage FOLFIRINOX + HAPa given every 14 days (alternate weeks of FOLFIRINOX) for up to 18 doses total. |
| Gemcitabine/Nab-Paclitaxel (SOC) Alone | Active comparator | Drug: FOLFIRINOX, Radiation: 5-FU Chemoradiation, Drug: Gemcitabine, Drug: Capecitabine, Drug: Nab-PaclitaxelArm 2B: Gemcitabine/Nab-Paclitaxel (SOC) Alone SOC Gem/Nab-Paclitaxel: nab-paclitaxel 125mg/m^2 IV over 30-40 minutes followed by gemcitabine 1000 mg/m^2 IV over 30-60 minutes for 3 weeks with 1 week rest. Given on days 1, 8, 15, 29, 36, 43, 57, 64 and 71 Day 71-80 Disease evaluated: New distant disease = salvage FOLFIRINOX given every 14 days Day 71-80 Disease evaluation: No disease = 5-FU or capecitabine plus Radiation (5-FU continuous IV infusion of 200-250 mg/m^2/day given 5-7 days each week over 5.5 weeks or Capecitabine 825 mg/m^2 PO BID M-F) concurrently with external beam radiation given at 1.8 Gy per fraction for 28 fractions total dose of 50.4 Gy Post-XRT Disease eval: surgically resectable = surgery + adjuvant SOC Gemcitabine Ineligible for surgical resection \& stable disease = continue gem/nab-paclitaxel given for 3 weeks (days 1, 8 and 15) with 1 week rest Ineligible for surgical resection \& progressive disease = salvage FOLFIRINOX given every 14 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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:
- Tumors considered to be unresectable due to local advancement include an absence of distant metastases as well as:
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FOLFIRINOXAlso: Oxaliplatin, Eloxatin®, Irinotecan, Camptosar®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 | Drug | FOLFIRINOX (SOC) ALONE, FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy, Gemcitabine/Nab-Paclitaxel (SOC) Alone, Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy |
| Algenpantucel-L ImmunotherapyAlso: HyperAcute®-Pancreas, HAPaAlgenpantucel-L Immunotherapy (HAPa) consisting of 300 Million HAPa cells given by intradermal injection | Biological | FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy, Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy |
| 5-FU ChemoradiationAlso: Fluorouracil, 5-Fluorouracil, 5-FU5-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 | Radiation | FOLFIRINOX (SOC) ALONE, FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy, Gemcitabine/Nab-Paclitaxel (SOC) Alone, Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy |
| GemcitabineAlso: GemzarGemcitabine 1000 mg/m^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. | Drug | FOLFIRINOX (SOC) ALONE, FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy, Gemcitabine/Nab-Paclitaxel (SOC) Alone, Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy |
| CapecitabineAlso: XelodaCapecitabine consisting of 825 mg/m^2 PO BID M-F concurrently with external beam radiation | Drug | FOLFIRINOX (SOC) ALONE, FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy, Gemcitabine/Nab-Paclitaxel (SOC) Alone, Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy |
| Nab-PaclitaxelAlso: Abraxane, PaclitaxelNab-Paclitaxel 125 mg/m^2 given intravenously over 30-40 minutes | Drug | FOLFIRINOX (SOC) ALONE, FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy, Gemcitabine/Nab-Paclitaxel (SOC) Alone, Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy |
Primary outcome
Overall Survival
Time frame: 13.5 months (assuming enrollment period of 1-2 years)
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.
3 secondary outcomes
Progression Free Survival
Time frame: 13.5 months (assuming enrollment period of 1-2 years)
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
Time frame: 13.5 months (assuming enrollment period of 1-2 years)
Immune Response
Time frame: 13.5 months (assuming enrollment period of 1-2 years)
Results and safety
The study was stopped early (reason given: Company decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2020.
- Derived from this study: PubMed 33630475Hewitt DB, Nissen N, Hatoum H, Musher B, Seng J, Coveler AL, Al-Rajabi R, Yeo CJ, Leiby B, Banks J, Balducci L, Vaccaro G, LoConte N, George TJ, Brenner W, Elquza E, Vahanian N, Rossi G, Kennedy E, Link C, Lavu H. A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer. Ann Surg. 2022 Jan 1;275(1):45-53. doi: 10.1097/SLA.0000000000004669.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
32 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing FOLFIRINOX, Algenpantucel-L Immunotherapy and 5-FU Chemoradiation in people with Pancreatic Cancer and Pancreatic Carcinoma Non-resectable, run by NewLink Genetics Corporation at 32 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Company decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 13.5 months (assuming enrollment period of 1-2 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01836432, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2020.