Immunotherapy Study in Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer (PILLAR)
Pancreatic Cancer, Pancreatic Carcinoma Non-resectable, Locally Advanced Malignant Neoplasm
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring Pancreatic Cancer, Immunotherapy, Vaccine Therapy
Eligibility Criteria
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:
- 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.
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.
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 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.
Sites / Locations
- Arizona Cancer Center
- Cedars-Sinai Medical Center
- Sutter Institute for Medical Research
- California Pacific Medical Center
- Stamford Hospital
- Boca Raton Regional Hospital
- University of Florida
- University of Miami
- USF Tampa General
- H. Lee Moffitt Cancer Center
- Illinois Cancer Specialists
- Indiana University Health Goshen Center for Cancer Care
- Indiana University
- University of Kansas Cancer Center
- University of Louisville
- Beaumont CCOP
- Virginia Piper Cancer Institute
- Renown Regional Medical Center
- Jersey Shore University Medical Center
- Mount Sinai Medical Center
- Wake Forest Baptist Health
- The Ohio State University
- University of Oklahoma
- Oregon Health and Science University
- Thomas Jefferson University
- University of Tennessee Medical Center
- University of Texas Southwestern Medical Center
- Baylor College of Medicine
- University of Virginia
- University of Washington - Seattle Cancer Center Alliance
- Vince Lombardi Cancer Center
- University of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Active Comparator
Experimental
Active Comparator
FOLFIRINOX + Algenpantucel-L (HAPa) Immunotherapy
FOLFIRINOX (SOC) ALONE
Gemcitabine/Nab-Paclitaxel+Algenpantucel-L HAPa Immunotherapy
Gemcitabine/Nab-Paclitaxel (SOC) Alone
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.
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
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.
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