A Phase III Study of Chemotherapy With or Without Algenpantucel-L (HyperAcute(RegisteredTM)- Pancreas) Immunotherapy in Subjects with Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer
This trial is an open-label, randomized, multi-institutional efficacy study. in this Phase iii trial, patients with borderline resectable or locally advanced unresectable pancreatic cancer will be randomized (1:1) to receive standard of care
FoLFiRinoX or gemcitabine/nab-paclitaxel with or without algenpantucel-L immunotherapy. The primary endpoint of the study is overall survival. The projected enrollment will be 280 subjects (140 chemotherapy + immunotherapy; 140 chemotherapy alone).
Patients will be randomized to receive to chemotherapy alone versus chemotherapy with algenpantucel-L in a 1:1 ratio. The randomization will be stratified by three factors; choice of backbone chemotherapy (FoLFiRinoX or gemcitabine/nab-paclitaxel) and a combination of disease stage (borderline resectable or locally advanced
unresectable) and baseline Ca19- tumor marker levels ([Less Than] 90 u/mL or [Greater Than] 90 u/mL). Disease stage and Ca19-9 tumor marker levels will be categorized as follows:
1. Borderline Resectable and Ca19-9 [Less Than] 90 u/mL
2. Locally advanced unresectable and Ca19-9 [Less Than] 90 u/mL or Borderline
Resectable and Ca19-9 [Greater Than] 90 u/mL
3. Locally advanced unresectable and Ca19-9 [Greater Than] 90 u/mL
The randomization process is designed to provide balance between the two treatment arms within each the chemotherapies (FoLFiRinoX versus gemcitabine/nab-paclitaxel) for the 3 levels of stratification listed above at each institution. The number of patients in each stratum level will not be restricted overall or within sites.
1. A histological diagnosis of adenocarcinoma of the pancreas confirmed by pathology.
2. 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:
3. Borderline resectable- Tumors considered borderline resectable are defined as follows:
a No distant metastases
b 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
c. 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.
d. Tumor abutment of the SMA not to exceed greater than 180 degrees of the circumference of the vessel wall.
4. Tumors considered to be unresectable due to local advancement include an absence of distant metastases as well as:
a. Head: Greater than 180 degrees SMA encasement or any celiac abutment or unreconstructible SMV/portal occlusion or aortic invasion or encasement.
b. Body: Greater than 180 degrees SMA or celiac encasement or unreconstructible SMV/portal occlusion or aortic invasion.
c. Tail: SMA or celiac encasement greater than 180 degrees.
d. 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.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status < 1. See Appendix B
6. Serum albumin > 2.0 gm/dL.
7. Expected survival > 6 months.
8. Adequate organ function including:
A. Marrow: WBC >3000/mm3 and platelets >100,000/mm3.
B. 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.
C. Renal: serum creatinine (sCr) <2.0 x ULN, or creatinine clearance (Ccr) >30 mL/min.
9. 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).
10. 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.