Immunotherapy Study in Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer

NCT01836432 | Terminated Phase 3 DMC

• 2 other identifiers: NLG05051210-1195
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 32

Brief 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

Keywords

Pancreatic Cancer; Immunotherapy; Vaccine Therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Progression Free Survival

  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

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

• Immune Response

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

Study Arms (4)

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.

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

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.

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

Drug: FOLFIRINOX; Radiation: 5-FU Chemoradiation; Drug: Gemcitabine; Drug: Capecitabine; Drug: Nab-Paclitaxel

Interventions

FOLFIRINOX DRUG

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

Also known as: Oxaliplatin, Eloxatin®, Irinotecan, Camptosar®, Leucovorin, Citrovorum factor, folinic acid, Fluorouracil, 5-Fluorouracil, 5-FU

FOLFIRINOX (SOC) ALONE; FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy; Gemcitabine/Nab-Paclitaxel (SOC) Alone; Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy

Algenpantucel-L Immunotherapy BIOLOGICAL

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

Also known as: HyperAcute®-Pancreas, HAPa

FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy; Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy

5-FU Chemoradiation RADIATION

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

Also known as: Fluorouracil, 5-Fluorouracil, 5-FU

FOLFIRINOX (SOC) ALONE; FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy; Gemcitabine/Nab-Paclitaxel (SOC) Alone; Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy

Gemcitabine DRUG

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

Also known as: Gemzar

FOLFIRINOX (SOC) ALONE; FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy; Gemcitabine/Nab-Paclitaxel (SOC) Alone; Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy

Capecitabine DRUG

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

Also known as: Xeloda

FOLFIRINOX (SOC) ALONE; FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy; Gemcitabine/Nab-Paclitaxel (SOC) Alone; Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy

Nab-Paclitaxel DRUG

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

Also known as: Abraxane, Paclitaxel

FOLFIRINOX (SOC) ALONE; FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy; Gemcitabine/Nab-Paclitaxel (SOC) Alone; Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• NewLink Genetics Corporation: lead

Study Sites (32)

Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Sutter Institute for Medical Research

Sacramento, California, 95816, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Stamford Hospital

Stamford, Connecticut, 06902, United States

Location

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

USF Tampa General

Tampa, Florida, 33606, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005, United States

Location

Indiana University Health Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Louisville

Louisville, Kentucky, 40292, United States

Location

Beaumont CCOP

Royal Oak, Michigan, 48073, United States

Location

Virginia Piper Cancer Institute

Minneapolis, Minnesota, 55407-3799, United States

Location

Renown Regional Medical Center

Reno, Nevada, 89502, United States

Location

Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Virginia

Charlottesville, Virginia, 22904, United States

Location

University of Washington - Seattle Cancer Center Alliance

Seattle, Washington, 98109, United States

Location

Vince Lombardi Cancer Center

Green Bay, Wisconsin, 54311, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• 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.

  PMID: 33630475 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

folfirinox; Oxaliplatin; Irinotecan; Leucovorin; Fluorouracil; Gemcitabine; Capecitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2013
• First Posted: April 19, 2013
• Study Start: May 1, 2013
• Primary Completion: July 29, 2016
• Study Completion: March 24, 2017
• Last Updated: May 28, 2020

Record last verified: 2020-05

Locations

US (32)