A Phase II Study of Paclitaxel Protein Bound + Gemcitabine + Cisplatin + Paricalcitol as Pre-operative Treatment in Patients With Untreated Resectable, Borderline Resectable and Locally Advanced Adenocarcinoma of the Pancreas
Phase: PHASE2
Conditions: Resectable Pancreatic Cancer, Unresectable Pancreatic Cancer, Pancreatic Adenocarcinoma, Neoadjuvant Pancreatic Cancer
Sponsor: HonorHealth Research Institute

Title: A PHASE II STUDY OF PACLITAXEL PROTEIN BOUND + GEMCITABINE + 
CISPLATIN+ PARICALCITOL AS PREOPERATIVE TREATMENT IN PATIENTS WITH 
UNTREATED RESECTABLE, BORDERLINE RESECTABLE AND LOCALLY 
ADVANCED ADENOCARCINOMA OF THE PANCREAS 
 NCT Number: NCT03138720 
 IRB Approval Date: March 25, 2020 (Initial protocol approval May 15, 2017) 

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A PHASE II STUDY OF PACLITAXEL PROTEIN BOUND + GEMCITABINE + 
CISPLATIN+ PARICALCITOL AS PREOPERATIVE TREATMENT IN PATIENTS WITH 
UNTREATED RESECTABLE, BORDERLINE RESECTABLE AND LOCALLY 
ADVANCED ADENOCARCINOMA OF THE PANCREAS 
IND Exempt 
SPONSOR 
HonorHealth Research Institute 
10510 N 92nd Street, Suite 200, Scottsdale, AZ, 85258 
VERSION DATE 
Amendment 4, Version 4.0, 17 February 2020 
Amendment 3, Version 3.2, 25 October 2018 
Amendment 2, Version 3.0, 20 February 2018 
Amendment 1, Version 2.0, 24 July 2017 
Original Protocol, Version 1.0, 16 February 2017 
CONFIDENTIAL 
The information contained in this document is confidential and the proprietary property of 
HonorHealth. Any unauthorized use or disclosure of such information without the prior 
written authorization of HonorHealth is prohibited. 

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INVESTIGATOR’S PROTOCOL AGREEMENT 
Protocol No.: 
NABPLAGEM-NEO 2017-001 
Version 4.0, 17 February 2020  
 
I confirm that my staff and I have carefully read and understand this protocol. I/we agree to 
comply with the procedures and terms of the study specified herein. In particular, I/we have 
agreed to: 
 
• 
Abide by all obligations stated on Form FDA 1572 and on other document(s) required by local 
regulatory authority. 
• 
Retain records and documents related to this Trial for at least 7 years after the last approval of a 
marketing application in an International Conference on Harmonization (ICH) region and until there 
are no pending or contemplated marketing applications in an ICH region or at least 7 years have 
elapsed since the formal discontinuation of clinical development of the investigational products. 
• 
Comply with Good Clinical Practice (GCP) and all applicable regulatory requirements. 
• 
Maintain confidentiality and assure security of HonorHealth confidential documents. 
• 
Obtain Institutional Review  Board (IRB) approval of the protocol, any amendments to the protocol, 
and periodic re-approval as required, and to keep the IRB informed of adverse events and 
periodically report the status of the study to them. 
• 
Not implement any deviations from or changes to the protocol without agreement from the Lead 
Sponsor-Investigator and HonorHealth and prior review and written approval from the IRB, except 
where necessary to eliminate an immediate hazard to the patients or for administrative aspects of the 
study (where permitted by all applicable regulatory requirements). 
• 
Assure that each patient enrolled into the Trial has read, understands, and has signed the Informed 
Consent. 
• 
Ensure that I and all persons assisting me with the study are adequately informed and trained about 
the investigational drug and of their study-related duties and functions as described in the protocol. 
• 
Make prompt reports of serious adverse events (SAEs) and deaths (within 1 business day of learning 
of the death and 2 business days of learning of the SAE) to HonorHealth. 
• 
Assure access by HonorHealth monitors, and/or FDA to original source documents. 
• 
Prepare and maintain adequate and accurate case histories designed to record all observations and 
other data pertinent to the investigation on each individual treated in the investigation. 
• 
Arrange for the transfer of appropriate data from case histories to case report forms for the collection 
and transmission of data to HonorHealth. 
• 
Cooperate fully with any study-related GCP audit as performed by HonorHealth quality assurance 
group. 
• 
Abide by the stipulations in the Disclosure of Data section and the manuscript preparation/authorship 
guidelines established at the outset of the study. 
Investigator’s Printed Name: 
Investigator’s Signature: 
Date: 
 
 

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SAE REPORTING 
 
All SAEs must be reported promptly to HonorHealth after the Investigator recognizes/ 
classifies the event as a SAE. For life-threatening or fatal events, the Investigator must 
report initial information on the SAE within 1 business day of becoming aware of the event, 
preferably by fax or alternatively by phone or email. 
 
HonorHealth Drug Safety Team 
24 Hour Phone #: 480-323-1350 
Fax #: 480-323-1560 
Email: DrugSafety@honorhealth.com 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
 
BACKGROUND AND RATIONALE ................................................................................... 8 
 
Pancreatic Cancer ....................................................................................................... 8 
 
Preoperative Therapy for Pancreatic Cancer ............................................................... 9 
 
Rationale for the use of paclitaxel protein bound, Gemcitabine, Cisplatin, and 
Paricalcitol ............................................................................................................................. 9 
 
Rationale for the use of CA19-9 as a primary endpoint. ..............................................10 
 
OBJECTIVES AND ENDPOINTS .....................................................................................11 
 
Primary Objectives ......................................................................................................11 
 
Secondary Objectives .................................................................................................11 
 
Exploratory Objectives ................................................................................................11 
 
STUDY POPULATION ......................................................................................................11 
 
Inclusion Criteria .........................................................................................................11 
 
Exclusion Criteria ........................................................................................................12 
 
Patient Enrollment.......................................................................................................13 
 
Patient Discontinuation ...............................................................................................13 
Cohort A 
Cohort B 

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Study Discontinuation .................................................................................................13 
 
STUDY TREATMENT .......................................................................................................14 
 
Treatment Pathways ...................................................................................................14 
 
Neoadjuvant Treatment ..............................................................................................14 
 
Administration and Dosing ..........................................................................................14 
 
Body Surface Area Calculation ............................................................................15 
 
Dose Modification for Toxicity ..............................................................................15 
 
Hematological Toxicity ..................................................................................16 
 
Non-hematological Toxicity ...........................................................................17 
 
Peripheral Neuropathy ..................................................................................18 
 
Nephrotoxicity ...............................................................................................18 
 
Cutaneous Toxicity .......................................................................................19 
 
Gastrointestinal Toxicity ................................................................................19 
 
Pulmonary Embolism ...........................................................................................19 
 
Prevention, Surveillance and Management of Interstitial Pneumonitis ..........19 
 
Hypersensitivity Reactions ...................................................................................20 
 
Colony Stimulating Factors ..................................................................................20 
 
Prophylaxis against Sepsis ..................................................................................20 
 
Intended Dose Delays ..........................................................................................20 
 
CONCOMITANT THERAPY..............................................................................................21 
 
Permitted Concomitant Therapy ..................................................................................21 
 
Concomitant Therapies Requiring Caution ..................................................................21 
 
Prohibited Concomitant Therapy .................................................................................21 
 
STUDY ASSESSMENTS ..................................................................................................22 
 
Screening ...................................................................................................................22 
 
On Study Assessments ...............................................................................................22 
 
End of Study ...............................................................................................................23 
 
Follow-Up Assessments..............................................................................................24 
 
EVALUATION OF RESPONSE ........................................................................................24 
 
CT Imaging .................................................................................................................24 
 
3D Volumetric Measurement and Histogram Analysis .................................................24 
 
Diffusion Weighted MRI Imaging .................................................................................24 
 
Biochemical Testing ....................................................................................................25 
 
Exploratory Biomarkers ...............................................................................................25 
 
16S Gut Microbiome rRNA Analysis ...........................................................................25 
 
Survival .......................................................................................................................26 

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Non-Evaluable ............................................................................................................26 
 
SAFETY ............................................................................................................................26 
 
Background.................................................................................................................26 
 
DEFINITION OF AN ADVERSE EVENT .....................................................................26 
 
DEFINITION OF A SERIOUS ADVERSE EVENT (SAE) ............................................27 
 
ADVERSE EVENT SEVERITY ...................................................................................28 
 
CAUSALITY ASSESSMENT .......................................................................................28 
 
SAFETY AND TOLERANCE ANALYSIS ....................................................................28 
 
PATIENT REPORTING OF AES AND SAES ..............................................................28 
 
INVESTIGATOR REPORTING OF AES AND SAES ..................................................29 
 
IRB Notification of SAEs .............................................................................................30 
 SAE Follow-Up ...........................................................................................................30 
 Sponsor Notification of Post-Study SAEs ....................................................................30 
 Pregnancy ..................................................................................................................30 
 
STATISTICS .....................................................................................................................30 
 
Treatment Assignment ................................................................................................30 
 
Patient Disposition ......................................................................................................30 
 
Patient Characteristics ................................................................................................31 
 
Statistical Considerations ............................................................................................31 
 ETHICAL, LEGAL AND ADMINISTRATIVE ASPECTS ...................................................31 
 Ethics ..........................................................................................................................31 
 Institutional Review Board/ Ethics Committee Approval .......................................31 
 Ethical Conduct of the Study ................................................................................32 
 Informed Consent .......................................................................................................32 
 Data Safety and Monitoring .........................................................................................32 
 Study Data Monitoring Plan ........................................................................................33 
 Data Safety and Monitoring Committee .......................................................................33 
 Confidentiality .............................................................................................................33 
 Publication ..................................................................................................................34 
 Protocol Compliance ...................................................................................................34 
 Quality Assurance .......................................................................................................34 
 On-site Audits .............................................................................................................35 
 Premature Closure of the Study ..................................................................................35 
 Investigator Documentation ........................................................................................35 
 
Form FDA 1572 ................................................................................................35 
 
Curriculum Vitae ...............................................................................................35 

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Financial Disclosures .......................................................................................35 
 Laboratory Certification and Normal Ranges ...............................................................35 
 Records Retention ......................................................................................................36 
 Protocol Deviations .....................................................................................................36 
 DATA MANAGEMENT .....................................................................................................36 
 Patient Enrollment Instructions....................................................................................36 
 Data Submission Instructions ......................................................................................36 
 TERMINATION OF STUDY ..............................................................................................37 
 INVESTIGATOR’S PROTOCOL AGREEMENT................................................................37 
 REFERENCES ..................................................................................................................37 
 SCHEDULE OF EVENTS .................................................................................................41 
 APPENDICES ...................................................................................................................42 
Appendix A: Abbreviations .................................................................................................42 
Appendix B:  Pathology Report ..........................................................................................44 
Appendix C: RECIST Target Lesion Response Criteria [Eisenhaur et al, 2009]. ................45 
APPENDIX D:  Study Drug Preparation, Dosing, Administration and Storage ....................46 
Appendix E:  2006 Update of ASCO Practice Guideline Recommendations for the Use of 
White Blood Cell Growth Factors: Guideline Summary ......................................................47 
APPENDIX F:  REVISED NATIONAL CANCER INSTITUTE COMMON TERMINOLOGY 
CRITERIA FOR ADVERSE EVENTS (NCI CTCAE), VERSION 4.0 (PUBLISHED 28 MAY 
2009) .................................................................................................................................50 
APPENDIX G:  KARNOFSKY PERFORMANCE STATUS .................................................51 
 APPENDIX H:  Memo for dexamethasone dose reduction with concomitant administration 
of fosaprepitant ..................................................................................................................51 
APPENDIX I:  The MD Anderson Symptom Inventory Gastrointestinal Cancer Module 
(MDASI-GI) (to be submitted separately from protocol for IRB approval) ...........................53 
APPENDIX J:  The Brief Pain Inventory (BPI) – Short Form (to be submitted separately 
from protocol for IRB approval) ..........................................................................................54 
APPENDIX K:  Fecal Samples for 16S Gut Microbiome rRNA Analysis                       
[Chaput et al 2017] ............................................................................................................55 
 
 
LIST OF TABLES 
Table 1: Dose Reductions Schema ...........................................................................................16 
Table 2: Dose Modifications for Day 1 of Each Cycle* ...............................................................16 
Table 3: Modification for Days 8 of Each Cycle .........................................................................17 
Table 4: Paclitaxel protein bound and gemcitabine and cisplatin - Dose Modifications for Day 1 
of Each Cycle (Non hematologic Toxicity)* ................................................................................17 
Table 5:  Paclitaxel protein bound and gemcitabine and cisplatin Dose Modifications Day 8 of 
Each Cycle (Non hematological Toxicity) ..................................................................................18 

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 BACKGROUND AND RATIONALE 
 
 
Pancreatic Cancer 
In 2020, the estimated number of new cases of pancreatic ductal adenocarcinoma (pancreatic 
cancer) in the US is 57,600 with an estimated 47,050 deaths from the disease [Siegel et al, 
2020]. Worldwide about 210,000 cases are diagnosed every year, however only 10-15% are 
surgical candidates and undergo a potentially curative operation. Generally, most new cases of 
pancreatic cancer are advanced with extensive tumor growth usually due to the lack of 
symptoms during the early stages of the disease. Even in the minority of patients who undergo 
surgical resection with a curative intent, there are few long term survivors. Current guidelines 
regarding patients with pancreatic cancer whose tumors are deemed resectable are to undergo 
resection and then to pursue adjuvant therapy. Adjuvant therapy with either gemcitabine or 5-
Fluoruracil (5-FU) is well established, and should be considered for patients who have 
recovered from surgery [Neoptolemos et al, 2004, Regine et al, 2008, Neoptolemos et al, 2004]. 
Recently, combination chemotherapy has been advised by NCCN guideline for adjuvant therapy 
for pancreatic cancer. A phase III trial reported that adjuvant gemcitabine plus capecitabine had 
a statistically significant improvement in survival compared to gemcitabine monotherapy with a 
median overall survival (mOS) of 28 versus 25.5 months (Neoptolemos et al, 2016). A phase III 
trial adjuvant combining 5-FU with leucovorin, oxaliplatin, and irinotecan (FOLFIRNOX)  a mOS 
of 54.4 months compared to 35.0 months (p=0.003) with gemcitabine alone in individuals with 
resected pancreatic cancer [Conroy et al 2018]. The addition of chemotherapy with radiation 
therapy is becoming less acceptable, as its improvement in overall survival is debatable. A 
recent meta-analysis of nine trials reported a worse overall survival with chemoradiation 

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compared to single agent gemcitabine or 5-FU [Liao et al 2013]. Investigators at Memorial Sloan 
Kettering Institute in NY published an analysis of a prospectively maintained database (1983-
2001) of 618 patients who underwent resection for pancreatic adenocarcinoma. There were only 
75 patients (12%) who survived > 5 years after resection, and 18 patients (5%) who survived 
>10 years. Stage and negative margins were associated with 5-year survival, and patients with 
stage IA disease had the best outcome with 5 year survival of 26% [Ferrone et al, 2008].  Thus, 
for patients with resectable disease overall survival still remains to be low.  
 
Preoperative Therapy for Pancreatic Cancer 
Neoadjuvant therapy has become the consensus treatment for individuals with locally advanced 
unresectable disease and borderline resectable disease [Seufferlein et al 2012].  Typical 
regimens utilize those that are used in the metastatic setting for pancreatic cancer, such as 
FOLFIRINOX (5-FU, Leucovorin, Irinotecan, and Oxaliplatin) and paclitaxel protein bound plus 
Gemcitabine. Currently, the recommendation of utilizing neoadjuvant therapy for potentially 
resectable pancreatic cancer has been met with controversy. However a recent study published 
an analysis of individuals with potentially resectable pancreatic cancer and showed a median 
overall survival of 31.5 months with 44.9 months for the 60 individuals who underwent 
neoadjuvant therapy and resection compared to 8.1 months for the 9 patients who were not 
resected [Christians et al 2016]. Another study examined the use of nab-paclitaxel, gemcitabine, 
capecitabine, and cisplatin (PAXG regimen) in individuals with unresectable or borderline 
resectable pancreatic cancer patients. A partial response was observed in 67% of the patients 
along with progression-free survival at 6 months being 96% [Reni et al 2016]. Furthermore, a 
recent study examining stage I or stage II pancreas cancer patients who received either 
neoadjuvant therapy followed by resection or those who received upfront resection was 
reported. In those receiving neoadjuvant therapy, overall survival was 26 months compared to 
21 months [Mokdad et al 2017]. Neoadjuvant, as opposed to adjuvant therapy potentially 
increases the amount of exposure of drug to the tumor. It allows for the completion of therapy 
prior to surgery to prevent patient drop-out due to perioperative complication. Neoadjuvant 
therapy also acts as a selection tool for optimal surgical candidates by identifying aggressive 
tumor biology prior to surgery and therefore selecting out those who will not benefit from 
resection. Radiation therapy may be also employed in the neoadjuvant setting as a means to 
help with local control and survival in individuals without micrometastatic disease.  
 
 
Rationale for the use of paclitaxel protein bound, Gemcitabine, Cisplatin, and 
Paricalcitol 
The combination of nab-paclitaxel (now called paclitaxel protein bound) and gemcitabine 
demonstrated an improvement in survival and response rate in advanced pancreatic cancer. In 
the phase III (MPACT study, n=861) patients were randomly assigned to nab-paclitaxel plus 
gemcitabine (431 patients) or gemcitabine (430). The median overall survival was 8.5 months in 
the nab-paclitaxel–gemcitabine group as compared with 6.7 months in the gemcitabine group 
(P<0.001). The one year survival rate was 35% in the nab-paclitaxel–gemcitabine group versus 
22% in the gemcitabine group, and 9% versus 4% at 2 years. The median PFS was 5.5 months 
in the nab-paclitaxel–gemcitabine group, as compared with 3.7 months in the gemcitabine group 
(P<0.001); the response rate according to independent review was 23% versus 7% in the two 
groups (P<0.001). Adverse events were tolerable with grade > 3 events of neutropenia (38% in 
the nab-paclitaxel–gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), 
and neuropathy (17% vs. 1%) and febrile neutropenia (3% versus 1%). Based on the results of 
this study, nab-paclitaxel plus gemcitabine is a FDA approved regimen for pancreatic cancer 
[Von Hoff et al 2013]. 
 
Building on the design and mechanisms of action of the nab-paclitaxel and gemcitabine 
combination, a prior protocol introduced a third cytotoxic agent cisplatin, was added to this 

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doublet [Jameson et al 2019]. The rationale for adding cisplatin to nab-paclitaxel and 
gemcitabine was that in a study of 1,029 patients whose pancreatic cancer tumors were sent for 
molecular profiling, 57% of these tumors were negative for ERCC1, indicating sensitivity to a 
platinum anti-tumor agent [Von Hoff 2012]. In addition to the above, in our whole 
genome/transcriptome sequencing analysis, we found that abnormal repair pathways were a 
feature of all of the pancreatic cancers that were sequenced [Liang et al 2012]. Cisplatin 
prevents cellular DNA repair by binding to and causing crosslinking of DNA, triggering 
apoptosis. Cisplatin has been used in other combination regimens to treat patients with PDA. 
For example, the cisplatin, epirubicin, 5-fluorouracil and gemcitabine (PEFG) regimen had an 
acceptable toxicity profile and was associated with a 24% partial response rate, 5 month 
progression-free survival (PFS) and 8.3 month overall survival as second line therapy [Reni et al 
2008].  
 
 
A team led by Gayle Jameson [Jameson et al, 2019] recently reported on the phase Ib/II trial of 
the combination of paclitaxel protein-bound plus gemcitabine plus cisplatin in advanced 
pancreatic cancer.  In 24 evaluable patients with stage IV pancreatic cancer they reported a 
response rate of 71% (Complete Response (CR) + Partial Response (PR)) along with an 88% 
disease control rate (CR + PR+ Stable Disease (SD) at 9 weeks).  Utilizing this highly active 
therapy in the neoadjuvant setting may lead to further improvement in overall survival and 
progression free survival in patients with pancreatic cancer. 
 
Most recently the spectacular work of Mara Sherman [Sherman et al 2014] has awakened the 
world of pancreatic cancer research to the possibility that Vitamin D could be a substantial 
player in normalizing the tumor microenvironment from an immunologically friendly (to the 
tumor) one to an immunologically hostile one (e.g. decreased IL6, decreased CXCL12 etc.). In 
addition, the vitamin D analog decreased production of collagen, decreased Myeloid Derived 
Suppressor cells (MDSCs) and decreased regulating T cells. In a completed neoadjuvant trial 
utilizing gemcitabine and paclitaxel protein bound with paricalcitol compared to gemcitabine and 
paclitaxel protein bound, a modulation of the tumor microenvironment has been seen including 
greater infiltration of CD3 positive lymphocytes (unpublished SU2C data courtesy of Drs. 
O’Dwyer and Drebin of the University of Pennsylvania). Therefore, a trial utilizing gemcitabine, 
paclitaxel protein bound, cisplatin and paricalcitol may yield promising results in the neoadjuvant 
setting. We conducted a prospective, phase 2 clinical trial of patients with resectable, borderline 
resectable, and locally advanced pancreatic cancer utilizing a regimen combining Paclitaxel 
protein bound (A) plus gemcitabine (G) plus cisplatin (C) plus paricalcitol (P).  Preliminary data 
of this study was presented at the AACR Pancreatic Cancer conference 2019 demonstrating a 
50% normalization rate of CA 19-9 out of the first 22 patients on the study ; 10 of the 22 patients 
proceeded with surgery, with an ORR 33% [Borazanci et al 2019]. As of December 2019, 
enrollment of the 24 patients planned for the study is complete. Grade 3 adverse events greater 
than 10% incidence related to therapy include anemia (59.1%), thrombocytopenia (50%). Grade 
4 adverse events related to therapy over 10% include thrombocytopenia (31.8%). Publication 
after final data analysis is pending.  
 
Rationale for the use of CA19-9 as a primary endpoint.  
Cancer Antigen 19-9 (CA 19-9) is the most commonly used serum biomarker for pancreas 
cancer. Several reports have indicated a sensitivity, specifity values at 80, 85 percent 
respectively [Steinberg 1990, Goonetilleke and Siriwardena 200]. Despite this, CA 19-9 remains 
the best tumor marker for pancreas cancer and its utility has been demonstrated in a few 
studies in the neoadjuvant setting. In a study examining patients with pancreas cancer with 
borderline resectable and locally advanced disease, those patients whose pre-operative CA 19-
9 were normalized (≤ 35 U/ml) had an overall survival of 71.4 months compared to those with an 

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elevated CA 19-9 (>35 U/ml) having an overall survival of 32.5 months [Williams et al 2016]. 
Another study in borderline resectable pancreatic cancer also demonstrated an improvement of 
overall survival in both the non-resected (15 months versus 11 months) and those who 
underwent resection (38 months versus 26 months) in those who had a normalized CA 19-9 
[Tzeng et al 2013]. Thus, the use of normalized CA 19-9 as a primary objective in a neoadjuvant 
trial may represent a significant insight to the overall clinical benefit of a given regimen.  
 
Based upon the encouraging preliminary results of this regimen, an additional 24 patients will be 
enrolled to further solidify the findings of the CA 19-9 normalization rate.   
 
 OBJECTIVES AND ENDPOINTS 
 
 
Primary Objectives 
• 
To evaluate: 
o The normalization rate of CA 19-9 of individuals with non-metastatic pancreas 
cancer following up to 6 months of neoadjuvant chemotherapy.  
 
 
Secondary Objectives 
 
• 
To assess: 
o Resectability (R0) rate following neoadjuvant chemotherapy 
o Pathologic Complete Response Rate (pCR) 
o Safety and tolerability of the neoadjuvant chemotherapy 
o Radiologic response rate  
o The 2 year survival from date of study entry 
 
 
Exploratory Objectives 
 
• 
To evaluate: cell-free DNA as biomarker for pancreatic cancer in relation to CA 
19-9 and/or clinical response by RECIST 1.1 
• 
To monitor and compare the gut microbial communities and to determine the 
differences in gut microbial communities within and between fecal samples using 
alpha and beta diversity metrics based on 16S rRNA sequencing. 
• 
To evaluate imaging biomarkers and tumor vascularity for response to therapy 
 
 
 STUDY POPULATION 
 
 
Inclusion Criteria 
 
1. Patient has histologically or cytologically confirmed resectable, borderline resectable, or 
locally advanced (unresectable) PDAC (based upon Tempero et al 2016) 
 
Definition of Resectable Pancreatic Cancer includes all of the following:  
o No evidence of extra pancreatic disease  
o No evidence of tumor-arterial abutment (celiac, SMA [superior 
mesenteric artery] or HA [hepatic artery])  
o If tumor induced narrowing of the SMV [superior mesenteric vein], PV 
[portal vein] or SMV-PV [superior mesenteric-portal vein] confluence 
is present, it must be <50% of the diameter of the vessel  
 
Definition of Borderline Resectable Pancreatic Cancer  

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o To include at least one of the following:  
o Tumor abutment <180° of the SMA or celiac axis  
o Tumor abutment or encasement of a short segment of the HA  
o Tumor induced narrowing of SMV, PV or SMV-PV of >50% of the 
diameter of the vessel.  
o Short segment occlusion of the SMV, PV or SMV-PV with a suitable 
PV above and SMV below, for reconstruction  
o Biopsy proven N1 disease (regional lymph nodes involved) from pre-
referral biopsy or EUS-guided FNA  
 
Definition of Locally Advanced (Unresectable) 
o Artery: Tumor encasement (> 180°) of SMA or celiac artery  
o Vein Occlusion of SMV, PV or SMV-PV without suitable vessels 
above and below the tumor to allow for reconstruction (no distal or 
proximal target for vascular reconstruction)  
o No extra pancreatic disease: No evidence of peritoneal, hepatic, or 
extra-abdominal metastases  
2. Age ≥ 18 years.  
3. If a female patient is of child-bearing potential, she must have a negative serum 
pregnancy test (≥β-hCG) documented within 72 hours of the first administration of study 
drug 
4. If sexually active, the patient and partner must agree to use contraception considered 
adequate and appropriate by the Investigator 
5. Patient must have received no prior chemotherapy or radiation therapy for PDAC  
6. Patients must have normal organ and marrow function as defined below: 
• 
absolute neutrophil count ≥ 1,500/mm3 
• 
platelets ≥ 100,000/mm3 
• 
Hematocrit level  > 27%  
• 
total bilirubin within 1.25 times institutional upper limit of normal (ULN) 
• 
AST/ALT ≤ 10 × institutional ULN 
 
• 
Creatinine < 1.5 mg/dl 
7. Patient has acceptable coagulation status as indicated by an INR ≤ 1.5 x ULN.  Patients 
on anticoagulation can be included at the discretion of the investigator. 
8. Karnofsky Performance Status (KPS) of ≥70%. 
9. Have an elevated CA 19-9  
 
 
Exclusion Criteria 
 
1. Patient will be excluded from this study if any of the following criteria apply: Evidence of 
metastatic disease. No metastatic disease defined as any one or more of the following: 
- Suspicious lymphadenopathy outside of the standard surgical field (i.e. aortocaval 
nodes, distant abdominal nodes) 
- Radiographic evidence for metastatic disease in distant organs, peritoneum, or ascites 
2. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy. 
3. Known infection with HIV, hepatitis B, or hepatitis C. 
4. Has undergone major surgery, other than diagnostic surgery (i.e.--surgery done to obtain 
a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of 
treatment in this study.  
5. History of allergy or hypersensitivity to the study drugs. 
6. Serious medical risk factors involving any of the major organ systems such that the 
Investigator considers it unsafe for the patient to receive an experimental research drug. 

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7. Current, serious, clinically significant cardiac arrhythmias as determined by the 
investigator. 
8. Patient is unwilling or unable to comply with study procedures. 
9. Patient is enrolled in an industry sponsored clinical trial  involving treatment with 
investigational therapy.  Patients enrolled in HonorHealth sponsored research studies 
may be eligible to participate as long as their participation in the other research studies 
does not confound the data collected for this study. 
10. Patient with a history of interstitial lung disease, history of slowly progressive dyspnea 
and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary 
hypersensitivity pneumonitis or multiple allergies. 
11. Use of non-FDA approved cannabinoids are prohibited.  Total daily usage of up to 40 mg 
per day of marinol is acceptable.  
 
 
 
 
Patient Enrollment 
 
This is an open-label study. A patient ID number will be assigned by the site when the patient 
signs the Informed Consent Form. A copy of the signed informed consent will be required for 
study entry. 
 
The exact date and time of each administration of medications will be recorded in the case 
report form (CRF). Paricalcitol, cisplatin, paclitaxel protein bound and gemcitabine will be 
administered according to the clinical study protocol only to patients who have given written 
informed consent. Patients withdrawn from the study will retain their patient ID number. New 
patients must always be allotted a new patient ID number. 
 
 
Patient Discontinuation 
 
Patients will be discontinued from the treatment under the following circumstances: 
1. Disease progression. 
2. Patient’s physician considers a change of therapy would be in the best interest of the 
patient.  
3. Patient requests discontinuation. 
4. Continued unacceptable toxicities despite optimal treatment or dose reduction.  
5. Patient becomes pregnant or fails to use adequate birth control (for those patients who 
are fertile). 
6. Need for any treatment not allowed by the protocol. 
7. Non-compliance. 
 
 
Study Discontinuation 
 
HonorHealth has the right to terminate the participation of either an individual site or the study at 
any time. Reasons for terminating the study include, but are not limited to, the following: 
 
1. 
Incidence or severity of AEs in this or other studies indicates a potential health 
hazard to patients. 
2. 
Patient enrollment is unsatisfactory. 
3. 
Investigator does not adhere to the protocol or applicable regulatory guidelines in 
conducting the study. 
 

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 STUDY TREATMENT 
 
 
Treatment Pathways 
 
All patients will be offered up to 6 months neoadjuvant therapy. For those who during therapy 
normalize their CA19-9 will be re-evaluated for surgery and will come off study. The patient will 
then proceed with standard of care therapy for their pancreatic cancer. Those completing 6 
months of neoadjuvant therapy will come off study and proceed with standard of care therapy 
for their pancreatic cancer.  
 
The recommended treatment will take into account input from the medical oncology 
investigators, patient performance status, co-morbidities, and contraindications. When 
necessary, other relevant factors concerning the patient’s clinical history and current medical 
literature will also be taken into consideration. The individual will be assessed through 
appropriate imaging, endoscopic evaluation, and surgical staging to determine resectability 
status and will undergo treatment based upon the following pathways.  
 
 
 
 
Neoadjuvant Treatment 
 
 
Each cycle of paricalcitol, paclitaxel protein bound, cisplatin and gemcitabine will last for 21 
days (see section 4.8 Administration and Dosing). 
 
Restaging will be done after 3 cycles. If progressive disease is noted the individual will be taken 
off study and undergo therapy at the discretion of the investigator.  
 
The patient may receive up to 6 months of study treatment.  
 
If the patient has a normal CA19-9 (i.e. ≤ 35 U/ml) the individual will be evaluated for surgery. If 
the patient’s tumor is deemed resectable then they will come off study for standard of care 
treatment.  
 
 
Administration and Dosing 
 
Treatment must be administered in a hospital, clinic or other out-patient setting appropriate for 
chemotherapeutic infusions. No investigational or commercial agents or therapies other than 
those described may be administered with the intent to treat the patient’s malignancy.  
 
The solution for infusion will be prepared at each investigational site. Detailed guidelines for the 
preparation and administration of paricalcitol, paclitaxel protein bound, cisplatin and gemcitabine 
are provided in Appendix D. An administration window of -5/+15 minutes is permitted. The order 
of infusion with premedication is as follows: 
 
Pre cisplatin hydration: up to 1000 mL with additional electrolytes as clinically indicated (i.e. 
Mannitol 12.5 grams and Magnesium Sulfate 2 grams) IV infusion over 2 hours on days 1 and 8 
repeated every 21 days.   
Palonosetron (Aloxi®) 0.25 mg IV, fosaprepitant (Emend®) 150 mg IV and dexamethasone 12 
mg IV, or equivalent antiemetic regimen, within 30 minutes prior to treatment on days patient is 
receiving paclitaxel protein bound + cisplatin + gemcitabine. (see Appendix H for details of 

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reduced dosing of dexamethasone with concomitant administration of fosaprepitant).  Patients 
will continue oral antiemetic prophylaxis at home with ondansetron 8 mg bid and 
dexamethasone 4 mg twice daily for 2 days after chemotherapy. Olanzapine 10 mg po at 
bedtime x 4 days after chemotherapy can be considered if additional antiemetic is needed. 
(Navari RM, et al, 2016.)  The type of antiemetic prophylaxis used can vary based on 
institutional procedures. 
 
Paclitaxel protein bound 125 mg/m2 over 30 minute IV infusion on days 1 and 8 repeated every 
21 days, followed by:  
 
Cisplatin 25 mg/m2 in 500* mL of 0.9% Sodium Chloride Injection over 60 minute IV infusion on 
days 1 and 8, repeated every 21 days, followed by: 
 
Gemcitabine 1000 mg/m2 in 250* mL 0.9% Sodium Chloride Injection over 30 minute IV 
infusion on days 1 and 8 repeated every 21 days 
 
Post cisplatin hydration: IV fluids up to 1000 mL (with additives as clinically indicated) IV given 
as infusion on days cisplatin is administered. This may start at the same time as the 
gemcitabine infusion. 
 
Paricalcitol will be given at a dose of 25 micrograms days 1 and 8 and repeated every 21 days  
 
* The investigator may reduce the volume of 0.9% Sodium Chloride Injection to 250 mL.  
 
In the event of extravasation during the infusion of paclitaxel protein bound, paricalcitol, cisplatin 
or gemcitabine, the infusion should be immediately terminated and patients treated according to 
local site protocols. The infusion should then be restarted in another vein. 
 
Doses may be rounded per institutional guidelines.  
 
 
 Body Surface Area Calculation 
 
The calculation of the dose of cisplatin, gemcitabine, and paclitaxel protein bound will be based 
on the patient’s body surface area (BSA) using the Mosteller formula (Verbraeken 2006). The 
BSA will be calculated at baseline and before each new cycle, based on the actual height and 
weight of the patient. The calculated dose will be rounded to the nearest whole milligram.  If 
there has been a ≥ 10% weight change from baseline, the drug doses will be recalculated based 
on the new BSA value.  If the change in weight is less than 10%, drug doses will not be 
recalculated. The dose of paricalcitol will be a flat 25 micrograms.   
 
 Dose Modification for Toxicity 
 
Toxicities will be graded using the NCI CTCAE v4.0 (see Appendix F). If toxicity occurs during 
or after any treatment cycle, the toxicity will be graded and appropriate supportive care 
treatment may be administered to decrease the signs and symptoms (e.g. antiemetics, 
antidiarrheals, antipyretics, antihistamines). 
 
For paclitaxel protein bound or gemcitabine or cisplatin or paricalcitol 
 

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Doses of paclitaxel protein bound and gemcitabine may be reduced in individual patients in 
accordance with the schedule in Tables 2, 3, 4, 5 and 6.  In general, doses that have been 
reduced for toxicity will not be escalated back to the starting level. Growth factors may be used 
to treat hematologic toxicity and will not constitute a dose reduction.  
 
 
 
Table 1: Dose Reductions Schema 
 
Dose Level 
paclitaxel 
protein bound 
(mg/m2) 
Cisplatin 
Dose** 
(mg/m2) 
Gemcitabine (mg/m2) 
Paricalcitol* 
(micrograms) 
Level - 0 
(baseline) 
125mg/m2 
25 
1000mg/m2 
25 
micrograms 
Level -1 
100mg/m2 
25 
800mg/m2 
25 
micrograms 
Level -2 
75mg/m2 
25** 
600mg/m2 
25 
micrograms 
*Note if any toxicity is deemed certainly relatable to the paricalcitol (e.g. renal stone, etc.) the 
paricalcitol will be discontinued 
**Note cisplatin should not be given unless creatinine is ≤ 1.5 X ULN 
 
 Hematological Toxicity 
 
In the event dose modifications are required at the beginning of a cycle or within a cycle due to 
hematologic toxicities, doses of paclitaxel protein bound, cisplatin, and gemcitabine may be 
adjusted as detailed in Table 1. Please note that all four drugs will be held at the start of a new 
cycle if Table 2 criteria are not met. Dosing delays up to 14 days are permitted for each cycle. 
Further dosing delays must be discussed with the principal investigator.  
 
Dose Modifications at Day 1 
 
Table 2: Dose Modifications for Day 1 of Each Cycle* 
*a cycle being defined as 21 days    
 
ANC 
 
Platelets 
Timing 
≥ 1.5 x 109/L 
And 
≥ 100 x 109/L 
Treat on time 
< 1.5 x 109/L 
Or 
< 100 x 109/L 
No treatment 
Dose Adjustments within a Treatment Cycle 
 
In the event that patients have missed doses within a treatment cycle due to hematologic 
toxicities, those doses not given during a cycle will not be made up. Dose modifications due to 

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hematologic toxicity (as represented by the blood counts and toxicities, below) within a 
treatment cycle should be adjusted as outlined in Table 3. 
 
Table 3: Modification for Days 8 of Each Cycle 
 
 
 
  
 
 
 
 
 
 Non-hematological Toxicity 
Dose reductions for non-hematologic toxicity that occur despite adequate background medical 
therapy should be undertaken in accordance with Table 5. 
 
  
Table 4: Paclitaxel protein bound and gemcitabine and cisplatin - Dose Modifications for Day 1 
of Each Cycle (Non hematologic Toxicity)* 
 
Non Hematologic Toxicity and/or Dose Hold with Previous Cycle 
Toxicity/dose held 
Paclitaxel protein bound + gemcitabine + cisplatin dose this cycle 
Day 8 
Laboratory  
Results 
Day 8  
Album-bound 
paclitaxel 
Day 8  
Cisplatin 
Day 8 
Gemcitabine 
Days 8  
Paricalcitol 
ANC > 1000  
and 
Platelets 
≥ 75,000 
100% 
100% 
100% 
100% 
ANC 500-1000a 
or Platelets 
50,000-74,999 
Decrease dose 
by 1 level  
(treat on time) 
100% 
Decrease dose 
by 1 level  
(treat on time) 
100% 
ANC < 500 
or 
Platelets < 
50,000 
Hold 
Hold 
Hold 
100% 
Febrile  
Neutropenia 
(Grade 3 or 4)b 
Hold. 
Upon resuming 
dosing, 
decrease 
to next lower 
dose level 
and do not re-
escalate 
throughout the 
rest of 
treatment 
Hold 
Hold. 
Upon resuming 
dosing, 
decrease 
to next lower 
dose level 
and do not re-
escalate 
throughout  
the rest of 
treatment 
100% 
Recurrent 
Febrile 
Neutropenia 
(Grade 3 or 4) 
Decrease 
2 dose levels  
(to 75 mg/m2) 
and do not 
re-escalate 
throughout  
the rest of 
treatment 
Hold 
Decrease 
2 dose levels  
(to 600 mg/m2) 
and do not 
re-escalate 
throughout  
the rest of 
treatment. 
100% 

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Grade 0, 1 or 2 
toxicity 
Same as Day 1 previous cycle (except for Grade 2 cutaneous toxicity 
where doses of paclitaxel protein bound and gemcitabine should be 
reduced to next lower dose level: please refer to Section 4.3.2.5). Note 
cisplatin should not be given unless creatinine is ≤ 1.5 mg/dl 
Grade 3 toxicitya,c 
Decrease paclitaxel protein bound and gemcitabine to next lower dose 
levela (see table 1) 
Grade 4 toxicity 
Off protocol treatment 
Dose held in 2 
previous consecutive 
cycles 
Decrease paclitaxel protein bound and gemcitabine to next lower dose 
level and continue throughout the rest of treatment 
* Excluding peripheral neuropathy (section 4.3.2.3) and nephrotoxicity (section 4.3.2.4). 
a If the toxicity only affects neuropathy, then only paclitaxel protein bound should be reduced 
(please see Section 4.3.2.3). 
b Pulmonary embolism (a Grade 4 toxicity in the CTCAE tables) if mild or asymptomatic, will be 
exempt from this requirement (please see Section 4.3.2.7). 
c Excluding electrolyte abnormalities per judgment of the physician/investigator. 
 
  
Table 5:  Paclitaxel protein bound and gemcitabine and cisplatin Dose Modifications Day 8 of 
Each Cycle (Non hematological Toxicity) 
 
CTC Grade 
Percent of Day 1 
paclitaxel protein bound + gemcitabine + cisplatin 
Dose 
0-2  
100%a 
3+  
Hold treatment until resolution to ≤ Grade 1 b,c.  
a Except for cutaneous toxicity: please refer to Section 4.3.2.5. 
b Pulmonary embolism (a Grade 4 toxicity in the CTCAE tables) if mild or asymptomatic, will 
be exempt from this requirement (please see Section 4.3.3). 
c Excluding electrolyte abnormalities per judgment of the physician/investigator. 
Please note when one drug is discontinued then it will be a matter of patient situation 
and clinical judgement as to whether some or all of the other agents are discontinued.  
  
 
 
 Peripheral Neuropathy 
 
Cisplatin and paclitaxel protein bound treatment should be withheld in patients who experience 
≥ Grade 3 peripheral neuropathy. Gemcitabine and paricalcitol administration can continue 
during this period. Cisplatin may be resumed at the same dose and paclitaxel protein bound 
treatment may be resumed at the next lower dose level in subsequent cycles after the 
peripheral neuropathy improves to ≤ Grade 1. The time to resolution to Grade ≤ 1 should be the 
adverse event duration used for adverse event reporting.  
 
 Nephrotoxicity 
 

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Cisplatin (cisplatin injection) produces cumulative nephrotoxicity which is potentiated by 
aminoglycoside antibiotics (see Appendix D). The serum creatinine, BUN, creatinine clearance, 
and magnesium, sodium, potassium, and calcium levels should be measured prior to initiating 
therapy, and prior to each subsequent course. Cisplatin should not be given unless serum 
creatinine is ≤ 1.5. 
 
 Cutaneous Toxicity 
 
Patients who develop Grade 2 or 3 cutaneous toxicity should have their dose reduced to the 
next lower dose level as per Table 4. If the patient continues to experience these reactions, 
despite dose reduction, treatment should be discontinued. Patients who develop Grade 4 
cutaneous toxicity should have treatment discontinued. 
 
 Gastrointestinal Toxicity 
 
If Grade 3 mucositis or diarrhea occurs, all 4 study drugs should be withheld until resolution to 
≤ Grade 1, then reinstituted at the next lower dose level as per Table 1. 
 
 Pulmonary Embolism 
 
Asymptomatic or clinically mild pulmonary embolism can be treated with low-molecular weight 
heparin without interruption of therapy. Moderate to severe pulmonary embolism will require 
permanent discontinuation of treatment. 
Interstitial Pneumonitis 
 
Pulmonary toxicity has been reported for gemcitabine and paclitaxel. Epidemiology reports 
show that gemcitabine monotherapy is weakly associated with lung toxicity. A retrospective 
review [Meadors et al, 2006] of pooled clinical trial data of 4,448 patients with mixed cancer 
indications reported an incidence of dyspnea of 0.2% and serious pulmonary toxicity of 0.06%. 
Paclitaxel monotherapy is weakly associated with lung toxicity ([Rowinsky and Donnehouer 
1995)]. Dyspnea with bronchospasm has been reported in 0.3 to 0.9%, with 30% of type 1 
hypersensitivity reactions. Combination chemotherapy of gemcitabine and paclitaxel protein 
bound shows a higher incidence of this complication compared to either drug alone but the two 
are no more than additive [Von Hoff et al, 2013].  
 
During study participation, patients should be carefully monitored for signs and symptoms of 
pneumonitis (i.e. episodes of transient or repeated dyspnea with unproductive persistent cough 
or fever) and, if observed, immediate clinical evaluation and timely institution of appropriate 
management (emphasizing the need for corticosteroids if an infectious process has been ruled 
out as well as appropriate ventilation and oxygen support when required). Administration of 
study drugs will be permanently discontinued upon making a diagnosis of interstitial 
pneumonitis. (See Section below) 
 
 Prevention, Surveillance and Management of Interstitial Pneumonitis 
 
During study treatment, episodes of transient or repeated dyspnea with unproductive persistent 
cough or fever should be paid attention to. Radiographic evaluation with chest X-rays and CT 
scans (normal or high resolution) may be indicated to look for infiltrates, ground-glass opacities 
or honeycombing patterns. Pulse oximetry and pulmonary function tests can show respiratory 
and ventilation compromise. 
 

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Infections should be ruled out with routine immunological/ microbiological methods. 
Transbronchial lung biopsy is not recommended, given its limited value and risk of 
pneumothorax and hemorrhage, and should be reserved for cases with unclear etiology. 
 
Study drug administration should be interrupted upon diagnosis of interstitial pneumonitis and 
patients permanently discontinued from further study drug treatment. After ruling out an 
infectious etiology, intravenous high-dose corticosteroid therapy and secondary pathogen 
coverage should be instituted without delay. Patients with an added immunological component 
may also require immune modulation with azathioprine or cyclophosphamide. Appropriate 
ventilation and oxygen support should be used when required. 
 
 Hypersensitivity Reactions 
 
Hypersensitivity reactions are not usually expected with cisplatin, paclitaxel protein bound or 
gemcitabine. If they do occur, minor symptoms such as flushing, skin reactions, dyspnea, 
hypotension, or tachycardia may require temporary interruption of the infusion. However, severe 
reactions, such as hypotension requiring treatment, dyspnea requiring bronchodilators, 
angioedema, or generalized urticaria require immediate discontinuation of the offending agent 
and aggressive symptomatic therapy. Patients who develop a severe hypersensitivity reaction 
should not be re-challenged. 
 
 Colony Stimulating Factors 
 
Based on the ASCO guidelines [Smith 2015] for use of granulocyte colony stimulating factors, 
(G-CSF) for regimens with at least a 20% risk of febrile neutropenia, pegfilgrastim will be 
administered subcutaneously on day 9 of each treatment cycle. G-CSF may also be given 
according to institutional guidelines for the treatment of neutropenic fever or infections 
associated with neutropenia and for the prevention of febrile neutropenia in patients with an 
ANC < 500 cells/μL. Patients not experiencing resolution of neutropenia within 21 days, despite 
uninterrupted G-CSF treatment, will discontinue study treatment.  
 
 Prophylaxis against Sepsis 
 
Due to the incidences of non-neutropenic sepsis, at the first occurrence of fever ≥ 38.5°C 
(regardless of neutrophil count), institution of ciprofloxacin (500 mg orally, twice daily) or 
amoxicillin/clavulanate (Augmentin®, 500 mg orally, 2-3 times daily) in patients with allergy to 
fluoroquinolones should be initiated. On their first visit, patients should be provided with enough 
ciprofloxacin (or the alternative antibiotic) for use at home, and they should be instructed to 
begin taking it when they first record a temperature of ≥ 38.5 °C (or if they feel they are 
developing a fever and a thermometer is not available). They should also immediately contact 
their physician for guidance on where to go for blood counts and to be evaluated for sepsis as 
soon as possible. Hospitalization or evaluation in the emergency room may be required 
depending on the clinical presentation. If hospitalization is required, please refer to Section 8.3 
of this protocol to report the event as a Serious Adverse Event (SAE). 
 
 Intended Dose Delays 
 
Intended cycles may be delayed for non-toxicity reasons for up to 14 days (for reasons such as 
scheduling conflicts), but only with documentation and explanation in the CRF after discussion 
with the study Principal Investigator. 
 

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 CONCOMITANT THERAPY 
 
 
Permitted Concomitant Therapy 
 
Necessary supportive measures for optimal medical care may be given throughout the study, 
including IV antibiotics to treat infections, blood components, and antiemetics. Additional care 
will be administered as indicated by the treating physician and the patient’s medical need. No 
concomitant cytotoxic therapy, whether conventional or investigational, will be allowed during 
this study. All concomitant medications and supportive therapy must be recorded on the 
appropriate CRF.  
 
Routine prophylactic use of a granulocyte colony-stimulating factor (G-CSF) will be used 
according to the American Society of Clinical Oncology guidelines (Appendix E), on Day 9 of the 
21 days cycle.  
 
The use of erythropoietin stimulating agents (ESA) is permitted if clinically indicated.  
 
 
Concomitant Therapies Requiring Caution 
 
Cisplatin nephrotoxicity may be exacerbated by treatment with other nephrotoxic drugs 
(e.g. aminoglycoside antibiotics, non-steroidal anti-inflammatory drugs). Caution with use of 
other nephrotoxic drugs. 
 
If anticoagulation with warfarin is necessary, frequent monitoring of prothrombin time and the 
International Normalized Ratio (INR) is recommended. Please see Appendix J for special 
precautions on the use of dexamethasone with concomitant fosaprepitant.  
 
 
 
Prohibited Concomitant Therapy 
 
No concomitant cytotoxic therapy, whether conventional or investigational, will be allowed 
during this study. 
 
Immunosuppressive corticosteroid use is not permitted while enrolled in the study. 
Corticosteroids for treatment or prevention of nausea and vomiting, or to modulate symptoms 
from an event of suspected immunologic etiology are permitted.  Inhaled (nasal or pulmonary), 
ophthalmic, topical steroids and local steroid injections are permitted. 
 
The use of vitamins or supplements that have reported use for the treatment or prevention of 
cancer, or that may interact with any of the study medications is not permitted. 
 
The use of medical marijuana (except FDA-approved therapy) in any formulation should be 
avoided while enrolled in this study. 
 
The use of additional vitamin D supplements while receiving study-administered paricalcitol 
should be avoided unless the patient is vitamin D deficient. 
 
 
 

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 STUDY ASSESSMENTS 
 
 
Screening 
 
1. Written informed consent  
2. Complete medical history including concurrent baseline conditions (using NCI CTCAE 
version 4.0; Appendix F), prior cancer therapy (including documentation of prior surgery, 
adjuvant or neoadjuvant chemotherapy and radiotherapy). 
3. Complete physical examination including height (cm) and weight (kg). 
4. Karnofsky Performance Status (KPS) (see Appendix G). 
5. Vital signs (blood pressure, pulse, respiratory rate, and temperature). 
6. Computed tomography (CT) / magnetic resonance imaging (MRI) scan to document 
disease status (including chest, abdomen, pelvis, and other regions as clinically 
indicated.  In addition, brain scan is required to exclude brain metastases if clinically 
indicated only). If a CT scan was taken within 28 days prior to first dose, a new scan is 
not necessary.  
7. Electrocardiogram (ECG). 
8. Hematology - Complete blood count (CBC) with differential and platelet count. 
9. Serum chemistries (for hepatic and renal function tests) including: blood urea nitrogen 
(BUN), phosphorus, magnesium, creatinine, creatinine clearance, total protein, albumin, 
calcium, glucose, total bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase 
(AST), alanine aminotransferase (ALT), and electrolytes (chloride, sodium, potassium, 
and bicarbonate). 
10. PT/INR 
11. CA19-9  
12. Provide fecal sample collection kit and review instructions with patient for return of sample 
within 48 hours of the next scheduled visit 
13. Urinalysis (lab); protein, specific gravity, glucose, and blood. 
14. Serum pregnancy test (if applicable). 
15. Concomitant medication notation (to include all medications taken within 30 days prior to 
enrollment). 
16. Archived tumor tissue, if available, will be obtained for further profiling work.  
17. Patient to complete MDASI-GI and BPI questionnaires 
 
Once eligibility is confirmed, a patient ID will be assigned and will be used throughout the trial. 
 
 
On Study Assessments 
 
Patients must begin Cycle 1 within 21 days of signing the IRB approved informed consent 
document and after the screening assessments. Treatment will be administered by qualified and 
trained site personnel in a hospital, clinic, or other outpatient setting appropriate for 
chemotherapeutic infusions. All assessments should be performed within 72-hours of each 
specified time parameter, with the exception of Cycle 1 in which assessments must be 
conducted within 24 hours (except those noted), or if medical or scheduling conditions require a 
delay.   
 
Day 1 of each cycle (except where noted) 
 
1. Inclusion/exclusion review (Cycle 1 only) 
2. Directed physical exam 

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3. Vital signs (blood pressure, pulse, respiratory rate, and temperature). 
4. Measurement of weight (kg)  
5. BSA calculation prior to dosing (After Cycle 1, the BSA only needs to be changed if there 
has been a change > 10% in body weight from Cycle 1 – Day 1 
6. Karnofsky Performance Status (KPS) (see Appendix G) 
7. Hematology: CBC with differential and platelet count 
8. Serum chemistries (for hepatic and renal function tests) including: blood urea nitrogen 
(BUN), phosphorus, magnesium, creatinine, creatinine clearance, total protein, albumin, 
calcium, glucose, total bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase 
(AST), alanine aminotransferase (ALT), parathyroid hormone (PTH) and electrolytes 
(chloride, sodium, potassium, and bicarbonate). 
9. CA19-9 
10. Blood sample for research for exploratory biomarkers  
11. Urinalysis (lab); protein, specific gravity, glucose, and blood 
12. Provide fecal sample collection kit and review instructions with patient for return of sample 
within 48 hours of the next scheduled visit. 
13. Serum Pregnancy (if applicable) 
14. AEs using the NCI CTCAE V4.0 (see Appendix F) 
15. Concomitant medication notation 
16. Patient to complete MDASI-GI and BPI questionnaires 
 
Day 8 and 15 of each cycle  
 
1. Directed physical exam  
2. Vital signs (blood pressure, pulse, respiratory rate, and temperature). 
3. Measurement of weight (kg) 
4. Karnofsky Performance Status (KPS) (see Appendix G) 
5. Hematology: CBC with differential and platelet count 
6. Serum chemistries (for hepatic and renal function tests) including: blood urea nitrogen 
(BUN), phosphorus, magnesium, creatinine, creatinine clearance, total protein, albumin, 
calcium, glucose, total bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase 
(AST), alanine aminotransferase (ALT), and electrolytes (chloride, sodium, potassium, 
and bicarbonate). 
7. AEs using the NCI CTCAE Version 4.0 (see Appendix F) 
8. Concomitant medication notation  
9. Patient to complete MDASI-GI and BPI questionnaires 
 
 
After Cycle 3, 6, 9 a CT/MRI scan to evaluate disease status using same imaging method as 
Baseline will be completed at the end of the cycle prior to starting the next cycle. 
 
Note: In order to more precisely determine time to progression, the investigator is encouraged to 
obtain radiological assessments and CA19-9 values earlier if there is a strong clinical suspicion 
of disease progression. In order to either confirm or refute the clinical impression. 
 
 
End of Study 
 
The patient will continue on study until there is normalization of CA 19-9, evidence of clear cut 
tumor progression, has treatment ending toxicities, completion of 6 months of therapy, or 
withdraws from treatment. The following assessments will be performed 14-28 (+/- 2) days after 
completing the last dose of trial therapy: 

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1. Directed physical exam 
2. Karnofsky Performance Status (KPS) (see Appendix G) 
3. Vital signs 
4. ECG 
5. Hematology: CBC with differential and platelet count 
6. Serum chemistries (for hepatic and renal function tests) including: blood urea nitrogen 
(BUN), phosphorus, magnesium, creatinine, creatinine clearance, total protein, albumin, 
calcium, glucose, total bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase 
(AST), alanine aminotransferase (ALT), and electrolytes (chloride, sodium, potassium, 
and bicarbonate). 
7. CA19-9  
8. Blood sample for research for exploratory biomarkers 
9. Urinalysis (lab); protein, specific gravity, glucose, and blood 
10. Concomitant medication  
11. AEs using the NCI CTCAE Version 4.0 (see Appendix F) 
12. Patient to complete MDASI-GI and BPI questionnaires 
 
If the patient goes to surgery, additional tissue will be obtained for further molecular analysis.  
 
 
Follow-Up Assessments 
 
Follow up assessments by telephone will be conducted for all patients or their families every 12 
weeks to determine the date of death. 
 
 
 EVALUATION OF RESPONSE 
 
 
CT Imaging  
 
Tumors will be assessed at the established staging intervals by CT scan of the abdomen/pelvis 
and CT of chest or Chest X-ray (if clinically indicated). Magnetic Resonance Imaging (MRI) or 
Magnetic Resonance cholangiopancreatography (MRCP) will be performed as clinically 
indicated. Treatment response will be classified by the RECIST version 1.1 criteria (see 
Appendix C). In addition, tumors will be assessed for conversion of tumor from borderline 
resectable to resectable based on clinical judgement.  
 
 
3D Volumetric Measurement and Histogram Analysis 
 
Post contrast CT images of the abdomen will be transferred into 3DQI imaging software (MGH 
in-house 3D software).  All thin reconstructed images will be uploaded into 3DQI workstation. 
Region of interest (ROI) will be drawn around tumor by using manual tool. Editing of ROI will be 
performed if needed. The pancreatic tumor based imaging biomarker will be defined by using 
the 3D QI software.  
 
 
Diffusion Weighted MRI Imaging  
 
A diffusion-weighted MRI of the abdomen will be performed by a commercially available 3.0 
tesla MRI system with a coil combination as appropriate for patient body habitus. The protocol 
will include standard T1 and T2 weighted sequences, in and out of phase imaging, and pre- and 
post-contrast imaging with the standard gadolinium-based contrast agents used in abdominal 

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imaging. A power injector will be used for the intravenous administration of the contrast agent to 
ensure correct timing of the early arterial, late arterial/parenchymal and venous phase. Diffusion 
weighted imaging will also be performed. Apparent diffusion coefficient (ADC) maps will be 
generated by the console from the diffusion weighted imaging data. The ADC map will be used 
to determine the hyper cellular/malignant portions of the tumor. Tumor response assessments 
will be made based on the anatomic and functional comparison of the tumors before and after 
therapy. MRI’s per physician discretion. 
 
 
Biochemical Testing  
 
CA19-9 will be evaluated serially in all patients with documented elevated CA19-9 at initial 
screening.  
 
 
Exploratory Biomarkers  
 
At Screening, individuals with core or fine needle aspirate (FNA) biopsies obtained previously 
will be obtained by the investigator’s site for further exploratory analysis if available. Up to a total 
of 7 micron slice slides will be obtained or a cellular block of tumor tissue. Future analysis will 
include PD-1, interferon gamma, and other immunological assays along with those that will 
assess for sensitivity to DNA repair targeted therapy. The sites may send the unstained core 
samples to HonorHealth to be stored at room temperature and will be analyzed at a later date.  
 
On Day 1 of every cycle, 20 mLs of blood will be collected for exploratory biomarker analyses 
until the patient stops participating in the study. These research samples will be stored for 
exploratory biomarker testing to be determined and conducted at a later date.  A research 
sample will also be collected at the End of Study visit.  In addition,   patients will be asked to 
consent to long term storage and future exploratory research testing for any left-over 
biospecimens collected during the study including archived tissue samples, blood samples 
and/or urine. 
 
 
16S Gut Microbiome rRNA Analysis 
 
The bacterial communities living in and on our bodies interact with our epithelial cells and can 
influence adaptive immunity, metabolic functions, and inflammation at a local and systemic 
level. The gut microbiota has been particularly well-studied and regulates the barrier functions of 
the gut epithelium, prevents pathogen or pathobiont overgrowth, facilitates metabolism of 
dietary fibers, and regulates metabolism. The gut microbiota may also influence the initiation, 
progression, and treatment of cancer including pancreatic [Ertz-Archambault et al 2017].  
Monitoring the microbiota in patients may enhance our ability to predict the likelihood of a 
positive patient response to therapy as well as indicators of adverse treatment effects and 
sensitive metrics of general patient health [Chaput et al 2017]. Given the possibility of altering 
the microbiome of a patient, future research is likely to include manipulating microbiotic 
communities to maximize the effectiveness of other therapies. 
Fecal samples are relatively easy to collect and non-invasive. They provide an indication of the 
gut microbiome which may be an indicator of general health, impact drug availability, and 
indicate the presence of communities associated with inflammation, digestive inefficiencies, and 
pathogens. Monitoring the gut microbiome may allow us to predict the risk of any possible side 
effects. 

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Survival  
 
PFS will be calculated only in patients who underwent resection, from the date of cytologic or 
histologic diagnosis until the date of recurrence or the last date at which the patient was known 
to be free of disease. OS will be calculated from the date of cytologic or histologic diagnosis 
until the date of death or last contact.  
 
OS and PFS will be calculated on all treated patients. Patients without disease progression at 5 
years will be censored at that time. Patients lost to follow-up without documented disease 
progression will be censored at the time of last contact. This is also true of patients 
discontinuing due to toxicity. Patients undergoing post-study therapeutic surgery/resection or 
radiation prior to progression will be censored at the initiation of that therapy if all macroscopic 
evidence of the tumor was resected. The date of progression will be the earlier of the dates of 
progression determined by CT or MRI imaging (increased lesion size, new metastases, new 
arterial/venous involvement) and rising CA19-9. 
 
 
Non-Evaluable 
 
A patient who completes at least 1 cycle of therapy will be deemed evaluable. Any patient 
deemed non-evaluable will be replaced. 
 
 SAFETY 
 
 
Background  
 
These AE management guidelines are intended to ensure the safety of each patient while 
attempting to characterize the safety and tolerability of the study drugs and procedures. In 
agreeing to the provisions of this protocol, the Investigator accepts all legal responsibilities for 
prompt notification of SAEs to the appropriate regulatory authorities. 
 
Adverse events occurring during the study will be graded according to the NCI Common 
Terminology Criteria for Adverse Events v4.0 (CTCAE) (see 
http://ctep.info.nih.gov/reporting/ctc.html), where applicable. The Investigator should evaluate all 
AEs and should make an immediate effort to determine their etiology. Non-serious AEs that are 
determined not to be possibly, probably, or definitely related to study drug may not require 
further evaluation but will need to be recorded in the patient's source document (e.g., patient 
hospital records, patient clinic charts, and laboratory reports). Grade 3 and 4 AEs must be 
recorded on the CRF. All SAEs without regard to causality must be promptly reported (within 24 
hours of knowledge of their occurrence) to HonorHealth Research Institute. Study medications 
may be interrupted for an AE at the discretion of the Investigator. Patients requiring toxicity 
management should be assessed and evaluated at least weekly as indicated by the severity of 
the event. AEs occurring following the signature of the informed consent, but prior to the first 
dose of study drug, will not be reported as AEs. 
 
 
DEFINITION OF AN ADVERSE EVENT 
 
An AE is any unfavorable medical occurrence in a patient receiving a marketed pharmaceutical 
product or in a patient who is participating in a clinical trial who is receiving an investigational or 
non-investigational pharmaceutical agent. The AE does not necessarily have a causal 

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relationship with the patient’s treatment. Therefore, an AE can be any unfavorable and 
unintended sign, symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered to be related to the medicinal product. In cancer clinical 
trials, many AEs are in fact related to progression of the patient’s underlying malignancy. 
 
An AE includes: 
• 
an exacerbation of a pre-existing illness; 
• 
an increase in frequency or intensity of a pre-existing episodic event or condition; 
• 
a condition detected or diagnosed after study drug administration even though it may 
have been present prior to the start of the study; 
• 
continuously persistent disease or symptoms that were present at baseline and worsen 
following the start of the study. 
 
An AE does not include: 
• 
medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, or 
transfusion); however, the condition that leads to the procedure is an AE. [Procedures 
that occur during the trial should be recorded on the Concurrent Procedure CRF];  
• 
pre-existing diseases, conditions, or laboratory abnormalities present or detected at the 
start of the study that do not worsen; 
• 
hospitalizations or procedures that are done for elective purposes not related to an 
untoward medical occurrence (e.g., hospitalizations for cosmetic or elective surgery or 
social/convenience admissions); 
• 
the disease being studied or signs/symptoms associated with the disease unless more 
severe than expected for the patient's condition; 
• 
overdose of study drug without any clinical signs or symptoms. 
 
 
DEFINITION OF A SERIOUS ADVERSE EVENT (SAE) 
 
An SAE is defined as any untoward medical occurrence at any dose that: 
• 
is fatal; 
• 
is life-threatening (defined as an immediate risk of death from the event as it occurred); 
• 
results in persistent or significant disability or incapacity; 
• 
requires in-patient hospitalization or prolongs an existing hospitalization. (Exception: 
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
during the study is not considered an SAE. NOTE: Complications that occur during 
hospitalization are AEs and if a complication prolongs hospitalization, then the event is 
serious); 
• 
is a congenital anomaly/birth defect in the offspring of a patient who received 
medication; 
• 
is a condition not included in the above definitions that may jeopardize the patient or 
may require intervention to prevent one of the outcomes listed above unless clearly 
related to the patient’s underlying disease. 
 
The Investigator should exercise medical and scientific judgment when deciding whether 
expedited reporting is appropriate in other situations not strictly meeting the criteria outlined 
above. Examples of important medical events which may also meet the definition of an SAE 
include: intensive treatment in an emergency room or at home for a reversible condition that did 
not result in hospitalization (e.g., allergic bronchospasm or convulsions), certain laboratory 
abnormalities (e.g., blood dyscrasias), or development of drug dependency or drug abuse. If 
there is any question, please consult the relevant Principal Investigator/Sponsor Investigator. 

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ADVERSE EVENT SEVERITY  
 
Adverse events occurring during the study will be graded according to the NCI Common 
Terminology Criteria for Adverse Events v4.0 (CTCAE) (see 
http://ctep.info.nih.gov/reporting/ctc.html), where applicable (see Appendix F). 
 
• 
Grade 1 – Mild AE 
• 
Grade 2 – Moderate AE 
• 
Grade 3 – Severe AE 
• 
Grade 4 – Life-threatening or disabling AE 
• 
Grade 5 – Death related to AE 
 
Severity versus Seriousness: Severity is used to describe the intensity of a specific event while 
the event itself, however, may be of relatively minor medical significance (such as severe 
headache). This is not the same as "seriousness," which is based on patient/event outcome at 
the time of the event. For example, the NCI CTCAE grade 4 (life-threatening or disabling AE) is 
assessed based on unique clinical descriptions of severity for each AE, and these criteria may 
be different from those used for the assessment of AE seriousness. An AE assessed as grade 4 
based on the NCI CTCAE grades may or may not be assessed as serious based on the 
seriousness criteria. 
 
 
CAUSALITY ASSESSMENT 
 
The relationship of an AE to the study drug must be classified as one of the following: 
Unrelated: The AE is clearly not related to the study medication 
Possibly Related: The AE may be related to the study medication 
Definitely Related: The AE is clearly related to the study medication 
 
 
 
SAFETY AND TOLERANCE ANALYSIS 
 
The incidence of all AEs (regardless of causality) and all treatment-related AEs (those AEs 
thought to be possibly, probably, or definitely related to study drug) will be summarized by NCI 
CTCAE Version 4.0 term and maximum grade. The incidence of SAEs and AEs that lead to 
discontinuation of study drug will also be summarized. Listings of patients who discontinue 
study drug due to an AE and patients with SAEs and deaths will be presented. Narratives will be 
provided for patients who experience an SAE. 
Lack of Efficacy is Not Considered an AE or SAE 
“Lack of efficacy” (progressive disease) is not considered an AE. The signs and symptoms or 
clinical sequelae resulting from lack of efficacy should be reported if they fulfill the AE or SAE 
definitions.  
 
 
PATIENT REPORTING OF AES AND SAES 
 
Patients are to be encouraged to call the site to report any unexpected symptoms or problems 
they encounter between office visits. These events should be considered in the same fashion as 
if they had been reported at a scheduled office visit. At each scheduled office visit, after the 
patient has had an opportunity to spontaneously mention any problems, the Investigator should 
inquire about AEs by asking the following standard questions: 

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Have you had any (other) medical problems since your last clinic visit? 
Have you taken any new prescribed or over-the-counter medicines or herbal/vitamin 
preparations, other than those given to you in this study, since your last visit/assessment? 
Have any new procedures been performed since your last study visit? 
 
 
 
INVESTIGATOR REPORTING OF AES AND SAES 
 
The Investigator is responsible for recording, reporting and following all Grade 3 or 4 AEs, 
regardless of causality, observed during the study period, starting with initial dose of study drug 
and ending at the time the patient goes off study or 30 days after patient’s last dose of study 
drug, whichever is later. The Investigator should follow AEs until the event is resolved or 
stabilized, the patient is lost to follow-up, or the event is otherwise explained. Events occurring 
within 30 days prior to study drug administration should be recorded as pre-treatment signs and 
symptoms. The only exception to this is for an AE that occurs prior to the first dose of study drug 
but is due to a procedure associated with assessments carried out to determine eligibility or to 
permit participation in this protocol – this should be recorded as an AE (rather than a pre-
treatment sign or symptom). 
 
The Investigator or designee must completely and promptly record each AE in the source 
documentation, regardless of relationship to study drug as determined by the Investigator. 
Grade 3 and 4 AEs must be recorded in the CRF. The Investigator must assess AE/SAE 
causality for any patients treated at his/her site and for any patients treated under the direct care 
of his/her sub-Investigators. The Investigator should attempt, if possible, to establish a diagnosis 
based on the patient's signs and symptoms. When a diagnosis for the reported signs or 
symptoms is known, the Investigator should report the diagnosis, not the symptoms, as the AE. 
 
Clinically significant laboratory abnormalities present at the baseline visit will be recorded as 
pre-treatment signs and symptoms. 
 
Grade 3 and 4 adverse events and SAEs should be reported on the appropriate case report 
forms. In addition, all SAEs must be reported promptly to HonorHealth Research Institute after 
the Investigator recognizes/classifies the event as a SAE. The specific reporting time frame 
depends on the type of SAE. For life-threatening or fatal events, the Investigator must report 
initial information on the SAE within 1 business day (24 hours) of becoming aware of the event, 
preferably by fax or alternatively by email on the HonorHealth Research Institute Reporting 
Form. At a minimum, a description of the event and the Investigator’s judgment of causality 
must be provided at the time of the initial report. For an event that is not life-threatening or fatal, 
the Investigator must fax or email a completed SAE report form within 2 business days after 
he/she recognizes/classifies the event as an SAE. 
 
The Grade 3 or 4 AE or SAE initial report must be as complete as possible, including details of 
the current illness and (serious) adverse event, and an assessment of the causal relationship 
between the event and the study drugs. Information not available at the time of the initial report 
(e.g., an end date for the adverse event or laboratory values received after the report) must be 
documented on the Follow-Up AE/SAE HonorHealth Research Institute Reporting Form. A final 
report to document resolution of the SAE is required. The Study protocol number and the 
institutional protocol number should be included on SAE reports to HonorHealth Research 
Institute. A copy of the fax transmission confirmation of the SAE report (or on the fax cover 
letter) sent to HonorHealth Research Institute should be attached to the SAE and retained with 
the patient records. 

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The Investigator should follow all AEs/SAEs observed from initial dosing up to 28 days after the 
last study drug administration until they resolve or stabilize, the patient is lost to follow-up, or the 
events are otherwise explained.  
 
 
IRB Notification of SAEs 
 
The Investigator is responsible for promptly notifying the IRB of all SAEs, including any follow-
up information, occurring at his/her site and any SAE regulatory reports and Investigational New 
Drug Safety Reports that he/she receives from HonorHealth Drug Safety. 
 
 
SAE Follow-Up 
 
For all SAEs occurring after first dose of study medication or within 30 days of the last 
administration of study medication, the investigator must submit follow-up reports to 
HonorHealth   or its representative regarding the status of the SAE and the patient’s subsequent 
course until the SAE has subsided, or until the condition stabilizes (in the case of persistent 
impairment), the patient receives alternative therapy, or the patient dies.  
 
 
Sponsor Notification of Post-Study SAEs 
 
The Investigator should notify HonorHealth of any death or SAE occurring after a patient has 
withdrawn from the study, or after 30 days of the last study drug dose, whichever is later, when 
such death or SAE may reasonably be related to the medication used in the study. However, 
Investigators are not obligated to actively seek AEs in former study participants. 
 
 
Pregnancy 
 
While not considered a SAE unless a serious criterion is met, pregnancies occurring in patients 
enrolled on the study or in their partners must be reported. The investigator should complete the 
pregnancy report form and fax it to Honor Health within 24 hours of knowledge of the 
pregnancy.  
 
 STATISTICS 
 
 
Treatment Assignment 
 
This is a Phase II open-label study with the identity of the treatment known to patients and 
investigators. 
 
 
Patient Disposition 
 
Summaries of patient disposition will include: 
 
• 
Patient discontinuation from treatment. 
• 
Patient discontinuation from study 
• 
Overall qualification status of all patients. 
 
All patients enrolled in the study will be included in the summation. The safety population will 
include all patients who have received at least one dose of any study drug. The number of 

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patients who do not qualify for analysis, who die or discontinue before treatment begins, will be 
summarized.  
 
 
Patient Characteristics 
 
Patient characteristics will include a summary of the following: 
 
• 
Patient demographics 
• 
Baseline disease characteristics 
• 
Pre-existing conditions 
• 
Prior therapies 
• 
Concomitant medications and treatments 
 
Other patient characteristics will be summarized as appropriate. 
 
 
Statistical Considerations  
 
The trial is a two-arm phase 2 study to design and assess a new treatment regimen. In total, 24 
patients with confirmed resectable will be enrolled in one arm and those with borderline 
resectable and locally advanced (unresectable) pancreatic ductal adenocarcinoma will be 
enrolled in the other arm. Patients will be stratified into one of two groups. Initial within-group 
comparisons will be conducted across patient characteristics. Two-tailed t tests or ANOVA tests 
will be conducted for parametric continuous variables. Non-parametric continuous variables will 
be compared using the Mann-Whitney U or Kruskal-Wallis tests. Pearson’s chi-squares test will 
be used to compare categorical data across treatment groups. 
 
As primary objectives, the rates normalization of CA19-9 in patients will be assessed. 
Secondary objectives include resectability rates (R0) following neoadjuvant chemotherapy and 
pathologic complete response rates (CR) will be evaluated using the RECIST criteria (Response 
Evaluation Criteria in Solid Tumors, see appendix C).  
 
Patients will be classified as CA19-9 non-responders if CA19-9 variation is < 50%; minor 
responders if CA19-9 variation is between 50 and 89%; and major responders if CA19-9 
variation is > 89% [Reni et al, 2009]. Overall survival will be calculated from the date of 
diagnosis until the date of death or last contact. For those who undergo resection, time to 
progression will be calculated from the date of cytologic or histologic diagnosis until the date of 
recurrence or the last date the patient was known to be free from disease. The Kaplan-Meier 
method will be selected to generate survival curves by clinical characteristics. Employing the 
log-rank test, researchers will assess differences between survival curves. Follow-up time is 
measured from time of diagnosis and the median will be calculated for all patients who survived 
since the time of last follow-up. Statistical tests are two-tailed, with a significance level of an 
alpha of 0.05. SPSS software version 24.0 will be used for all statistical analyses. 
 
 
  ETHICAL, LEGAL AND ADMINISTRATIVE ASPECTS 
 
 
Ethics 
 
 Institutional Review Board/ Ethics Committee Approval  
 

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Before study initiation, this protocol and informed consent form will be submitted for review and 
approval to the IRBs charged with oversight for the clinical sites. In addition, any form of 
proposed advertising and advertising text for patient recruitment must be reviewed and 
approved by HonorHealth prior to submission to the IRB. The Investigator will forward to 
HonorHealth or Sponsor-nominated designee a copy of the IRB’s approval of this protocol, any 
amendments, informed consent form, and any modifications to the informed consent, based on 
the FDA regulations set forth in 21 CFR 56 of the Code of Federal Regulations, as well as those 
of the applicable regulatory bodies in all other participating countries outside of the U.S.  
In addition, the Investigator will be responsible for forwarding to HonorHealth or 
Sponsor-nominated designee a description of the IRB board members (including profession and 
affiliation) or a United States (US) Department of Health and Human Services (DHHS) General 
Assurance number and expiration date. If neither of these is available, the chairperson must 
submit a statement indicating that the members of the board responsible for the review meet 
FDA and other appropriate regulatory requirements. In addition, the labeling for all approved 
study drugs should be submitted to the IRB for informational purposes. 
 
Clinical supplies will not be shipped to the clinical site until IRB approval is obtained for the 
protocol. Any existing amendments, informed consent, and photocopies of the approved 
documents must be received by HonorHealth or other sponsor-nominated designee prior to 
drug shipment. 
 
 Ethical Conduct of the Study 
 
This study will be conducted in compliance with the protocol, Good Clinical Practice (GCP), 
Guidelines of the International Conference on Harmonization (ICH) of Technical Requirements 
for Registration of Pharmaceuticals for Human Use, and in full compliance with the World 
Medical Association Declaration of Helsinki and its most recent amendments. 
 
 
 
 
Informed Consent 
 
Written informed consent of the patient to participate in the study must be obtained and 
documented by the Investigator in accordance with the FDA regulations set forth in 21 CFR 50 
as well as the applicable regulatory bodies in all other participating countries outside the United 
States.  
 
The Investigator must provide the patient with a copy of the informed consent form in a 
language understandable to the patient. Written consent should be obtained before any 
protocol-required procedures are performed, including any procedure not part of normal patient 
care (e.g., withdrawal of current medications). 
 
Changes made by a participating site to the recommended informed consent must be must be 
forwarded to HonorHealth for approval prior to submission to the corresponding IRB. A copy of 
the signed informed consent will be given to the patient or their legal representative and a copy 
must be retained in the Investigator’s study records.  
 
 
Data Safety and Monitoring 
 
This treatment regimen combines 3 chemotherapeutic agents with known toxicity profiles. 
Because cancer is a life-threatening disease, treatments that result in Grade 3 and 4 toxicities 

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are considered to have an acceptable risk profile. Data reported to HonorHealth Research 
Institute will be received by the Lead Principal Investigator on a regular basis and not less than 
once a month. In addition, SAEs will be reported to HonorHealth immediately and reviewed as 
they are received. Any unacceptable toxicities or severe toxicities that occur more frequently 
than expected will be discussed by the study Principal Investigator who will decide jointly 
whether the study should be modified, interrupted, or stopped. A monthly conference call will be 
held with investigators participating in the study. The statistical group will provide listings of 
toxicities on a regular basis. 
 
 
 
Study Data Monitoring Plan 
 
HonorHealth ensures that appropriate monitoring procedures are performed before, during and 
after the study. Before the study is initiated at a site visit or at an investigator meeting, all 
aspects of the study are reviewed with the Investigator and the staff. Prior to enrolling patients 
into the study, a HonorHealth representative will review the protocol, CRFs, procedures for 
obtaining informed consent, record keeping, and reporting of AEs/SAEs with the Investigator. 
Monitoring will include on-site visits with the Investigator and study team as well as any 
appropriate communications by mail, email, fax, or telephone.  
 
Data monitoring procedures will be carried out by HonorHealth for all participating sites, and will 
be performed on a regular basis to comply with Good Clinical Practice guidelines.  
Review of the case report forms, cross-reference with source documentation (including 
radiology review), review of study related regulatory documents and logs (e.g., enrollment, study 
site staff, drug accountability), and review of drug accountability will be monitored on an ongoing 
basis during monitoring sessions. The monitor will ensure that the investigation is conducted 
according to protocol design and regulatory requirements.  
 
At the conclusion of the monitoring visit, the site monitor will meet with the site staff to discuss 
and request specific corrections to the case report forms, and/or request clarification, and/or 
additional source documentation. The site Clinical Research Coordinator responsible for the 
study will be provided with a copy of the written monitoring notes for resolution of the findings.  
 
The HonorHealth site monitor will complete a written monitoring report and forward it to the site 
Principal Investigator and to HonorHealth Administration. The report will include a summary of 
what the site monitor reviewed and the site monitor’s statements concerning the significant 
findings/facts, deviations and deficiencies, conclusions, actions taken or to be taken, and/or 
actions recommended to ensure compliance. The site Principal Investigator will be expected to 
submit any Corrective Action Plans, in writing, to HonorHealth Administration and the 
HonorHealth site monitor. A copy of the monitoring forms, final monitoring reports, and 
Corrective Action Plan will be kept in the site monitor’s study file at HonorHealth for follow-up at 
the next monitoring session. 
 
 
Data Safety and Monitoring Committee  
 
This study will not utilize the services of a Data Safety and Monitoring Committee 
 
 
Confidentiality 
 
The Investigator and any other study personnel involved in this study shall not disclose, or use 
for any purposes (other than for the performance of this study), any data, records, or other 

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information (hereinafter collectively “information”) disclosed to the Investigator or other study 
personnel. Such information shall remain the confidential and proprietary property of 
HonorHealth, and shall be disclosed only to the Investigator or other designated study 
personnel.  
 
The obligation of non-disclosure shall not apply to the following: 
 
• 
relevant disclosure to potential study participants for the purpose of obtaining informed 
consent; 
• 
information after such time that it is or becomes publicly available through no fault of the 
Investigator or other study personnel; and 
• 
information after such time that it is disclosed to the Investigator by a third party entitled 
to disclose such information. 
• 
If the study site is a ‘covered site’ under the definitions of the Health Insurance Portability 
and Accounting Act (HIPAA), the Investigator will ensure that the patient consents to the 
use of data by  HonorHealth and its designees for the purposes of regulatory 
submissions, study publications, and drug approval. 
 
 
Publication 
 
The Investigator(s) shall have the right, consistent with academic standards and with due regard 
to the protection of HonorHealth confidential information and intellectual property, to publish or 
present the results of work performed in accordance with the study; provided that any proposed 
publication or presentation is first reviewed and approved in writing by HonorHealth shall 
complete its review within 60 days after receipt of the proposed publication or presentation. 
Upon HonorHealth request, proposed publication or presentation will be delayed up to 60 
additional days to enable HonorHealth to secure adequate intellectual property protection of 
property of HonorHealth that would be affected by such proposed publication or presentation. If 
HonorHealth believes in good faith that any proposed publication or presentation contains any 
confidential information and/or intellectual property HonorHealth shall have the right to remove 
references to any such confidential information and/or intellectual property.  
 
 
Protocol Compliance 
 
The investigator will conduct the study in compliance with the protocol given approval/favorable 
opinion by the IRB/IEC and the appropriate regulatory authority(ies). Changes to the protocol 
will require approval from HonorHealth, in addition to written IRB/IEC approval/favorable opinion 
prior to implementation, except when the modification is needed to eliminate an immediate 
hazard(s) to patients. The IRB/IEC may provide, if applicable regulatory authority(ies) permit, 
expedited review and approval/favorable opinion for minor change(s) in ongoing studies that 
have the approval /favorable opinion of the IRB/IEC. The investigator will submit all protocol 
modifications to HonorHealth and the regulatory authority(ies) in accordance with the governing 
regulations. Any departures from the protocol must be fully documented in the source 
documents. 
 
 
Quality Assurance 
 
All aspects of the study will be carefully monitored by HonorHealth and/or its authorized 
representative for compliance with applicable government regulations with respect to current 
ICH GCP guidelines as well as other applicable regulations and guidelines.  

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 On-site Audits 
 
Regulatory authorities, the IEC/IRB, and/or HonorHealth may request access to all source 
documents, data capture records, and other study documentation for on-site audit or inspection. 
Direct access to these documents must be guaranteed by the investigator, who must provide 
support at all times for these activities. 
 
 Premature Closure of the Study 
 
This study may be prematurely terminated, if in the opinion of the Lead Principal Investigator or 
HonorHealth there is sufficient reasonable cause.  
 
HonorHealth has the right to discontinue the study under the conditions specified in the clinical 
Trials agreement. Written notification documenting the reason for study termination will be 
provided to the site investigator by the terminating party.  
 
Circumstances that may warrant termination include, but are not limited to: 
 
• 
Determination of unexpected, significant, or unacceptable risk to patients  
• 
Failure to enter patients at an acceptable rate  
• 
Insufficient adherence to protocol requirements  
• 
Insufficient complete and/or evaluable data  
• 
Plans to modify, suspend or discontinue the development of the drug  
• 
Should the study be closed prematurely, all study materials must be returned to 
HonorHealth. 
 
 
 Investigator Documentation 
 
 
Form FDA 1572 
 
As this study has been determined to be IND Exempt and this is not a multi-center study, a 
1572 will not be completed. 
 
 
Curriculum Vitae 
 
The Investigator must provide HonorHealth with his/her current signed and dated curriculum 
vitae and a current signed and dated curriculum vitae for each sub-Investigator. Current signed 
and dated curriculum vitae is defined as updated within 2 years of study start up. 
 
 
Financial Disclosures 
 
As a 1572 will not be completed for this study, Financial Disclosure forms will not be required or 
collected. 
 
 Laboratory Certification and Normal Ranges 
 
The Investigator will provide a copy of all clinical laboratory certifications, certification numbers, 
dates of certifications, and a list of the normal ranges for all laboratory tests for all facilities 

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listed. Updated versions of these documents must be provided to HonorHealth as appropriate. 
In the event the clinical laboratory is changed during the study, the study Principal Investigator 
will be notified. Appropriate documentation will be submitted to HonorHealth to verify the 
certification of the new laboratory. 
 
All radiology facilities being utilized outside the investigative site must be pre-approved by 
HonorHealth. 
 
 Records Retention 
 
In accordance with applicable regulatory requirements, following closure of the study, the 
Investigator will maintain a copy of all site study records in a safe and secure location.  
HonorHealth will inform the Investigator of the time period for retaining these records in order to 
comply with applicable regulatory requirements. 
 
HonorHealth reserves the right to terminate the study for refusal of the Investigator and/or 
investigational site to comply with any requirements stated in this study protocol. 
 
 Protocol Deviations 
 
Deviations from the protocol must be addressed as protocol amendments with IRB approval 
required prior to implementation. Apart from the regulatory requirements, it is vital to the 
success of the study that the Investigator adheres to the details of the protocol and thus holds to 
a minimum the number of cases that may be later classified as “incomplete,” “unusable,” or “not 
evaluable.” 
 
 
 
   DATA MANAGEMENT 
 
 
Patient Enrollment Instructions 
 
Patients must be registered within 5 working days prior to initiation of protocol therapy. This 
study uses a web based patient enrollment system for data submission through the data 
management services of HonorHealth Patient enrollment materials. 
 
 
Data Submission Instructions 
 
This study uses a electronic data capture system for data submission through the data 
management services of HonorHealth.  The original reports, traces and films must be retained 
by the Investigators for future reference. 
 
• 
Screening Form: at time of screening 
• 
Enrollment Form: after eligibility confirmed.  
• 
All screening/baseline/treatment/off-treatment Forms: within 2 weeks of occurrence.  
• 
Adverse Event Form: within 2 weeks of each scheduled adverse events evaluation until 
adverse events have resolved following permanent discontinuation of treatment, 
documenting adverse event information, including toxicities indicated by lab testing.  
 
NOTE: all Serious Adverse Events must also be reported on the Adverse Event Form. 

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Serious Adverse Events (SAE) documentation: submit directly to HonorHealth and the Site 
Principal Investigator within the time frame and per the guidelines specified in Section 8.8.  
 
NOTE: all SAEs must also be reported on the Adverse Event Form. 
 
Notice of Death Form: within 2 weeks of knowledge of death. 
 
 
 TERMINATION OF STUDY 
 
HonorHealth reserves the right to discontinue this study at any time. 
 
 
 INVESTIGATOR’S PROTOCOL AGREEMENT 
 
The Investigator must sign the Investigator’s Protocol Agreement (Page 3 of this document). 
The original must be kept on file at HonorHealth and the Investigator must retain a copy. The 
completed Investigator’s Protocol Agreement signifies agreement to comply with all procedures 
outlined by this protocol by the Investigator. An Investigator’s Protocol Agreement must be 
signed if and when a protocol amendment is issued by HonorHealth. 
 
 
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pancreatic cancer. British Journal of Cancer 109, 926-933: 2013  
 
Borazanci E, Jameson G,  Snyder C, Tsai F,  Gordon M,  Sharma S,  Gaurnieri C,  Thosani A, 
Rahmanuddin S,  Korn R,  Sckolnik S,  Sedivy P,  Haag S,  Gosselin K,  Von Hoff D, and  Amini 
A. Paclitaxel protein bound (A) plus gemcitabine (G) plus cisplatin (C) and paricalcitol 
(P)neoadjuvant therapy for localized pancreatic ductal adenocarcinoma (PDAC). Presented at 
Pancreatic Cancer: Advances in Science and Clinical Care, September 7, 2019. 
 
Cameron JL, Riall TS, Coleman J, et al: One thousand consecutive 
pancreaticoduodenectomies. Ann Surg. 2006; 244:10-5. 
 
Chaput N, Lepage P, Coutzac C, Soularue E, Le Roux K, Monot C, Boselli L, Routier E, 
Cassard L, Collins M, Vaysse T, Marthey L, Eggermont A, Asvatourian V, Lanoy E, Mateus C, 
Robert C, Carbonnel F. Baseline gut microbiota predicts clinical response and colitis in 
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Christians KK, Heimler JW, George B, Ritch PS, Erickson BA, Johnston F, Tolat  
PP, Foley WD, Evans DB, Tsai S. Survival of patients with resectable pancreatic 
cancer who received neoadjuvant therapy. Surgery. 2016 Mar;159(3):893-900. 
 
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Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J,  Sauvanet A, Breysacher 
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JL, Juzyna B, Gourgou S, O'Callaghan CJ, Jouffroy-Zeller C, Rat P, Malka D, Castan F, Bachet 
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Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018 Dec 
20;379(25):2395-2406. 
 
Desai N, Trieu V, Yao Z, et al. Increased antitumor activity, intratumor paclitaxel concentrations, 
and endothelial cell transport of cremophor-free, paclitaxel protein bound, Nab-paclitaxel, 
compared with cremophor-based paclitaxel. Clin Cancer Res. 2006; 12:1317-24. 
 
Eisenhauera E., Therasseb, P., Bogaertsc, J., et al. New response evaluation criteria in solid 
tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009; 45:228-247. 
 
Ertz-Archambault N, Keim P, Von Hoff D. Microbiome and pancreatic cancer: A comprehensive 
topic review of literature. World J Gastroenterol. 2017 Mar 14;23(10):1899-1908. 
 
Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation 
for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008; 
26(21):3496-502).  
 
Evans DB, Rich TA, Byrd DR, et al. Preoperative chemoradiation and 
pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992; 127:1335-39. 
 
Ferrone CR, Brennan MF, Gonen M, et al. Pancreatic adenocarcinoma: the actual 5-year 
survivors. J Gastrointest Surg. 2008; 1:701-6. 
 
Fine RL, Fogelman DR, Sherman W, et al. The GTX regimen: a biochemically syndergistic 
combination for advanced pancreatic cancer (PC). Proc Am Soc Clin Oncol. 2003; 22:281. 
(Abstract 1129). 
 
Glynne-Jones R, Wallace M, Livingstone JI, et al. Complete clinical response after preoperative 
chemoradiation in rectal cancer: is a "wait and see" policy justified? Dis Colon Rectum. 2008; 
51:10-9. 
 
Goonetilleke KS, Siriwardena AK. Systematic review of carbohydrate antigen (CA 
19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg 
Oncol. 2007 Apr;33(3):266-70 
 
Gradishar W J, Tjulandin S, Davidson N, et al. Phase III Trial of Nanoparticle Paclitaxel protein 
bound Compared With Polyethylated Castor Oil-Based Paclitaxel in Women With Breast 
Cancer. J Clin Oncol. 2005; 23:7794-803. 
 
Guweidhi A, Kleef J, Adwan H, et al. Osteonectin influences growth and invasion of pancreatic 
cancer cells. Ann Surg. 2005; 242: 224-34. 
 
Heinrich S, Pestalozzi BC, Schäfer M, et al. Prospective phase II trial of neoadjuvant 
chemotherapy with gemcitabine and cisplatin for resectable adenocarcinoma of the pancreatic 
head. J Clin Oncol. 2008; 26:2526-31.  
 
Jameson GS, Borazanci E, Babiker HM, Poplin E, Niewiarowska AA, Gordon MS, Barrett MT, 
Rosenthal A, Stoll-D'Astice A, Crowley J, Shemanski L, Korn RL, Ansaldo K, Lebron L, 
Ramanathan RK, Von Hoff DD. Response Rate Following Albumin-Bound Paclitaxel Plus 
Gemcitabine Plus Cisplatin Treatment Among Patients With Advanced Pancreatic Cancer: A 

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Phase 1b/2 Pilot Clinical Trial. JAMA Oncol. 2019 Oct 3. doi: 10.1001/jamaoncol.2019.3394. 
[Epub ahead of print]. 
 
Liao WC, Chien KL, Lin YL et al. Adjuvant treatments for resected pancreatic adenocarcinoma: 
a systematic review and network meta-analysis. Lancet Oncol. 2013 Oct;14(11):1095-103. 
 
Liang WS, Craig DW, Carpten J et al. Genome-wide characterization of pancreatic 
adenocarcinoma patients using massively parallel sequencing. PLos ONE. 2012 Oct 
10;7(10):e43192. 
 
 MacKenzie S, Zeh H, McCahill, LE . A pilot phase II multicenter study of nab-paclitaxel (Nab-P) 
and gemcitabine (G) as preoperative therapy for potentially resectable pancreatic cancer (PC).  
J Clin Oncol 31  (suppl; abstr 4038) 2013. 
 
Mokdad AA, Minter RM, Zhu H, Augustine MM, Porembka MR, Wang SC, Yopp AC, 
Mansour JC, Choti MA, Polanco PM. Neoadjuvant Therapy Followed by Resection 
Versus Upfront Resection for Resectable Pancreatic Cancer: A Propensity Score 
Matched Analysis. J Clin Oncol. 2016 Sep 12. 
 
Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine 
alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer 
Institute of Canada, Clinical Trials Group [NCIC-CTG]. JCO 25: 1960, 2007. 
 
Navari, RM, Qin R, Ruddy KJ, et al. (2016). Olanzapine for the Prevention of Chemotherapy-
Induced Nausea and Vomiting. NEJM 375:134-42. 
 
Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and 
chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200-10. 
 
Neoptolemos JP, Palmer D, Ghaneh P, et al.ESPAC-4: A multicenter, international, open-label 
randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine 
(GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected 
pancreatic ductal adenocarcinoma. 2016 ASCO Annual Meeting | Abstract No: LBA4006, | 
Category: Gastrointestinal (Noncolorectal) Cancer - Pancreatic Cancer. 
 
Nyman DW, Campbell KJ, Hersh E, et al. A Phase I and pharmacokinetics trial of nab-
paclitaxel, a novel formulation of paclitaxel stabilized with human serum albumin, administered 
weekly for 3 doses every 4 weeks in patients with advanced non-hematologic malignancies. J 
Clin Oncol. 2005; 23:7785-93. 
 
Oettle H, Arnold D, Hempel C, et al. The role of gemcitabine alone and in combination in the 
treatment of pancreatic cancer. Anticancer Drugs. 2000; 11:771-86. 
 
Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before 
and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma : 
a randomized controlled trial. JAMA. 2008;299:1019-26. 
 
Reni M, Cereda S, Mazza E et al. PEGF (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) 
regimen as second-line therapy in patients with progressive or recurrent pancreatic cancer after 
gemcitabine-containing chemotherapy. Am J Clin Oncol. 2008;31:145-150. 
 

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Reni, M., Balzano, G., Zanon, S. et al. (2016). Phase 1B trial of Nab-paclitaxel plus 
gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or 
borderline resectable pancreatic adenocarcinoma. British Journal of Cancer, 115(3), 290-296. 
 
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Seufferlein T, Bachet JB, Van Cutsem E, Rougier P; ESMO Guidelines Working 
Group. Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for 
diagnosis, treatment and follow-up. Ann Oncol. 2012 Oct;23 Suppl 7:vii33-40. 
 
Siegel R., Miller K, and Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017;67:7–30 
 
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Tempero M et al. NCCN Clinical Professional Guidelines. Pancreatic Adenocarcinoma. Version 
2.2016. https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf  
 
Therasse P, Arbuck SG, Eisenhauer EA, et al: New guidelines to evaluate the response to 
treatment in solid tumors. J Natl Cancer Inst. 2000; 92:205-16. 
 
Tiruppathi C, Finnegan A, Malik AB: Isolation and characterization of a cell surface albumin-
binding protein from vascular endothelial cells. Proc Natl Acad Sci USA 93(1) 250-54, 1996 
Von Hoff DD, Ramanathan R, Borad M, et al. Gemcitabine plus nab-paclitaxel is an active 
regimen in patients with advanced pancreatic cancer: A phase I/II trial. J Clin Oncol. 29:4548-
4554.2011 
 
Tzeng CW, Balachandran A, Ahmad M, Lee JE, Krishnan S, Wang H, Crane CH, Wolff 
RA, Varadhachary GR, Pisters PW, Aloia TA, Vauthey JN, Fleming JB, Katz MH. Serum 
carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy  
in patients with borderline resectable pancreatic cancer. HPB (Oxford). 2014 
May;16(5):430-8. 
 
Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-
paclitaxel plus gemcitabine. N Engl J Med. 369: 1691-703: 2013. 
 
Von Hoff DD, Ramanathan RK, Evans DB et al. Actionable targets in pancreatic cancer 
detected by immunohistochemistry (IHC), microarray (MA) fluorescent in situ hybridization 
(FISH), and mutational analysis. J Clin Oncology. 2012;30s: abstr 4013. 
 
Williams JL, Kadera BE, Nguyen AH, Muthusamy VR, Wainberg ZA, Hines OJ, Reber  
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 SCHEDULE OF EVENTS 
 
 
 
 
Assessments 
 
 
Screening 
 
Cycle 
21 days 
End of 
Cycle 
(EOC)/ 
End of 
Treatment 
(EOT)11 
 
 
Survival 
FU 
 
Day 1 
 
Day 8 
 
Day 9 
 
Day 15 
Day-21 
± 3 
days 
± 3 days 
± 3 days 
± 3 days 
± 2 days 
± 7 days 
Signed Informed Consent 
X 
 
 
 
 
 
 
Review Inclusion/Exclusion 
Criteria 
X 
X10 
 
 
 
 
 
Medical History 
X 
X 
 
 
 
 
 
Directed Physical Exam1 
X 
X 
X 
 
X 
X 
 
Height (cm) 
X 
 
 
 
 
 
 
Weight (kg) 
X 
X 
X 
 
X 
X 
 
BSA Calculation 
 
X 
 
 
 
 
 
Vital Signs2 
X 
X 
X 
X 
X 
X 
 
Karnofsky PS 
X 
X 
X 
 
X 
X 
 
CT/MRI/Tumor 
Measurements 
X12 
 
 
 
 
X9 
 
ECG 
X 
 
 
 
 
X 
 
Hematology3 
X 
X 
X 
 
X 
X 
 
Serum Chemistries4 
X 
X 
X 
 
X 
X 
 
CA19-9  
X 
X 
 
 
 
X 
 
Biomarker Blood Sample 
 
X 
 
 
 
X 
 
Fecal Sample Collection 
X13 
X13 
 
 
 
 
 
PT/INR 
X 
 
 
 
 
 
 
Urinalysis5 
X 
X 
 
 
 
X 
 
Serum Pregnancy6 
X 
X 
 
 
 
 
 
Con Meds 
X 
X 
X 
X 
X 
X 
 
Adverse Events 
 
X 
X 
X 
X 
X 
 
Subject Questionnaires7 
X 
X 
X 
 
X 
X 
 
Paclitaxel protein bound 
 
X 
X 
 
 
 
 
Cisplatin 
 
X 
X 
 
 
 
 
Gemcitabine 
 
X 
X 
 
 
 
 
Paricalcitol 
 
X 
X 
 
 
 
 
Pre-cisplatin hydration 
 
X 
X 
 
 
 
 
Post-cisplatin hydration 
 
X 
X 
 
 
 
 
Neulasta 
 
 
 
X 
 
 
 
Telephone Call 
 
 
 
 
 
 
X8 
1. 
Complete Physical Exam completed on Day 1 
2. 
Blood pressure, pulse, respiratory rate and temperature 
3. 
Includes CBC with differential and platelet count 
4. 
Includes blood urea nitrogen (BUN), phosphorus, magnesium, creatinine, creatinine clearance, total protein, albumin, 
calcium, glucose, total bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase 
(ALT), and electrolytes (chloride, sodium, potassium, and bicarbonate. Parathyroid hormone (PTH) levels will be checked 
on D1 of every cycle.  
5. 
Includes protein, specific gravity, glucose, and blood 
6. 
For women of child bearing potential 
7. 
Includes MDASI-GI and BPI questionnaires 
8. 
every 12 weeks until confirmation of death 
9. 
Only at the end of Cycles 3, 6 and 9 
10. Cycle 1 only 
11. EOT assessments to be completed within 14-28 days from the last dose of medication 
12. If a CT scan was completed within 28 days of the first dose, does not need to be repeated. 
13. To be returned to site within 48 hours of collection. 
 
 
 

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  APPENDICES 
 
APPENDIX A: ABBREVIATIONS 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
ALT (SGPT) 
Alanine Aminotransferase (SGPT) 
ANC 
Absolute Neutrophil Count 
AST (SGOT) 
Aspartate Aminotransferase (SGOT) 
AUC 
Area Under the Curve 
β-hCG 
Beta subunit of human chorionic gonadotrophin (hCG) 
BMS 
Bristol-Myers Squibb 
BSA 
Body Surface Area 
BUN 
Blood Urea Nitrogen 
CA19-9 
Carbohydrate Antigen 19-9 
CBC 
Complete Blood Count 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CIB 
Clinical Investigator’s Brochure 
CMH 
Cochran-Mantel-Haenszel 
CrEL 
Cremophor-EL 
CRF 
Case Report Form  
CR 
Complete Response 
CRO 
Contract Research Organization 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DHHS 
Department of Health and Human Services 
DLT 
Dose Limiting Toxicity 
DVT 
Deep Vein Thrombosis 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EPR 
Enhanced Permeability and Retention 
EORTC 
European Organization for Research and Treatment of Cancer 
EOS 
End of Study 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice(s) 
G-CSF 
Granulocyte Colony-Stimulating Factor 
GFR 
Glomerular Filtration Rate 
GTX 
Gemzar plus Taxotere plus Xeloda 
HA 
Human Albumin 
Hgb 
Hemoglobin 
ICH 
International Conference on Harmonisation 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IV 
Intravenous(ly) 
KPS 
Karnofsky Performance Status 
LDH  
Lactate Dehydrogenase 
MR 
Minor Response 
MRI 
Magnetic Resonance Imaging 

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MTD 
Maximum Tolerated Dose 
NCI 
National Cancer Institute 
ND 
Not Done 
NIH 
National Institutes of Health 
non-DEHP  
Non-(di(2-ethylhexyl) phthalate) 
PD 
Progressive Disease 
PET 
Positron-Emission Tomography 
PK 
Pharmacokinetics 
PR 
Partial Response 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious Adverse Event 
SD 
Stable Disease 
S.D. 
Standard Deviation 
SGOT 
Serum Glutamate Oxaloacetic Transaminase 
SGPT 
Serum Glutamate Pyruvic Transaminase 
SOP 
Standard Operating Procedure 
SPARC 
Secreted Protein Acidic and Rich in Cysteine (a glycoprotein) 
SUV 
Standard Uptake Value 
ULN 
Upper Limit of Normal  
US 
United States 
WBC 
White Blood Cell 
WHO 
World Health Organization 

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APPENDIX B:  PATHOLOGY REPORT 
Provide a copy of the pathology report, surgical operative note with the following form 
completed. Please follow the AJCC staging system, 7th edition1. 
1. Margin status Per Frozen Section Diagnosis 
a. R0 resection (margin negative) 
b. R1 resection (margin positive)  
c. R2 grossly positive 
 
2. The tumor sample has (Ref: Evans DB et al2) 
a. No tumor destruction 
b. Grade I: 1-9 % of tumor destruction 
c. Grade II: 10-90% of tumor destruction 
d. Grade III: > 90% of tumor destruction. 
e. Grade IV: absence of viable tumor cells. 
 
3. TNM staging - Primary Tumor (T) 
a. TX  
Primary tumor cannot be assessed 
b. T0 
No evidence of primary tumor 
c. Tis  
Carcinoma in situ 
d. T1 
Tumor limited to the pancreas, 2 cm or less in greater dimension 
e. T2 
Tumor limited to the pancreas, more than 2 cm in greatest dimension 
f. T3 
Tumor extends beyond the pancreas but without involvement of the celiac 
axis or  superior mesenteric arterya 
g. T4 
Tumor involves the celiac axis or the superior mesenteric artery 
(unresectable  primary tumor 
 
*For T3, extension beyond the pancreas may include invasion of soft tissues adjacent to 
the pancreas, the extrapancreatic biliary system, and/or duodenum (including the 
ampulla of Vater). Specifically, peripancreatic tissues include the surrounding 
retroperitoneal fat (retoperitoneal soft tissue), including mesentery (mesenteric fat), 
mesocolon, greater and lesser omentum, and peritoneum. 
 
4. Regional Lymph Nodes (N) 
a. NX  
Regional lymph nodes cannot be assessed 
b. N0 
 No regional lymph node metastasis         Total number of lymph nodes 
harvested _____ 
c. N1 
Regional lymph node metastasis                
 
5. Distant Metastasis (M) 
a. M0 
No distant metastasis  
b. M1 
Distant metastasis 
 
 
 
 

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APPENDIX C: RECIST TARGET LESION RESPONSE CRITERIA [EISENHAUR ET 
AL, 2009]. 
 
RECIST Target Lesion Response Criteria v1.1  
Target Response 
Criteria 
Definition 
Complete Response 
(CR) 
Disappearance of all target lesions. Any pathological lymph 
nodes (whether target or non-target) must have reduction in 
short axis to <10 mm 
Partial Response (PR) 
At least a 30% decrease in the sum of diameters of target 
lesions, taking as reference the baseline sum of diameters. 
Stable Disease (SD) 
Neither sufficient shrinkage to qualify for PR nor 
sufficient increase to qualify for PD. 
Progressive Disease 
(PD) 
At least a 20% increase in the sum of diameters of target 
lesions, taking as reference the smallest sum on study (this 
may include the baseline sum). The sum must also 
demonstrate an absolute increase of at least 5 mm. 
 
 
 

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APPENDIX D:  STUDY DRUG PREPARATION, DOSING, ADMINISTRATION AND 
STORAGE 
See links below to website access 
Paclitaxel protein bound (Abraxane™) Prescribing Information (Updated 7/2015) – Accessed via 
Abraxane Website: http://www.abraxane.com/wp-
content/uploads/Abraxane_Prescribing_Information.pdf  
Gemcitabine (Gemzar™) Prescribing Information (Updated 6/2014) – Accessed via Gemzar 
Website: http://pi.lilly.com/us/gemzar.pdf 
Cisplatin (Platinol®) Prescribing Information (updated 9/2010) – Accessed Cisplatin FDA 
website http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018057s080lbl.pdf  
Paricalcitol (Zemplar®) Prescribing Information (10/2016) – Accessed via Zemplar Website 
http://www.zemplar.com/  
 
 
 

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APPENDIX E:  2006 UPDATE OF ASCO PRACTICE GUIDELINE 
RECOMMENDATIONS FOR THE USE OF WHITE BLOOD CELL GROWTH 
FACTORS: GUIDELINE SUMMARY 
Setting/Indication 
Recommendation 
Primary prophylaxis 
Primary prophylaxis is recommended for the prevention of FN in 
patients who have a high risk of FN based on age, medical 
history, disease characteristics, and myelotoxicity of the 
chemotherapy regimen. For “dose-dense” regimens, CSF is 
required and recommended. Clinical Trial data support the use 
of CSF when the risk of FN is in the range of 20% or higher.  
Primary prophylaxis: 
Special circumstances 
Certain clinical factors predispose to increased complications 
from prolonged neutropenia, including: patient age > 65 years; 
poor performance status; previous episodes of FN; extensive 
prior treatment including large radiation ports; administration of 
combined chemoradiotherapy; bone marrow involvement by 
tumor-producing cytopenias; poor nutritional status; the 
presence of open wounds or active infections; more advanced 
cancer, as well as other serious comorbidities. In such situations, 
primary prophylaxis with CSF is often appropriate, even with 
regimens with FN rates of < 20%.  
Secondary prophylaxis 
Secondary prophylaxis with CSF is recommended for patients 
who experienced a neutropenic complication from a prior cycle 
of chemotherapy (for which primary prophylaxis was not 
received), in which a reduced dose may compromise disease-
free or overall survival or treatment outcome. In many clinical 
situations, dose reduction or delay may be a reasonable 
alternative. 
Therapeutic use: 
Afebrile neutropenia 
CSF should not be routinely used for patients with neutropenia 
who are afebrile. 
Therapeutic use: 
Febrile neutropenia 
CSF should not be routinely used as adjunctive treatment with 
antibiotic therapy for patients with fever and neutropenia. 
However, CSF should be considered in patients with fever and 
neutropenia who are at high-risk for infection-associated 
complications, or who have prognostic factors that are predictive 
of poor clinical outcomes. High-risk features include expected 
prolonged (> 10 days) and profound (< 0.1 × 109/L) neutropenia, 
age > 65 years, uncontrolled primary disease, pneumonia, 
hypotension and multi-organ dysfunction (sepsis syndrome), 
invasive fungal infection, or being hospitalized at the time of the 
development of fever. 
Dose intensity/density 
of chemotherapy 
Dose-dense regimens should only be used within an 
appropriately designed clinical Trial or if supported by convincing 
efficacy data. 

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Setting/Indication 
Recommendation 
Adjuncts to progenitor-
cell transplantation 
Administration of CSF to mobilize PBPC often in conjunction with 
chemotherapy, and their administration after autologous, but not 
allogeneic, PBPC transplantation is the current standard of care. 
AML: Initial or repeat 
induction chemotherapy 
CSF use following initial induction therapy is reasonable, though 
there has been no favorable impact on remission rate, remission 
duration, or survival. Patients > 55 years of age may be most 
likely to benefit from CSF use. 
AML: CSF for priming 
effects 
Use of CSF for priming effects is not recommended. 
AML: Consolidation 
chemotherapy 
CSF use can be recommended after the completion of 
consolidation chemotherapy because of the potential to 
decrease the incidence of infection and eliminate the likelihood 
of hospitalization in some patients receiving intensive 
postremission chemotherapy. There seems to be more profound 
shortening of the duration of neutropenia after consolidation 
chemotherapy for patients with AML in remission than for 
patients receiving initial induction therapy. As yet there is no 
information about the effect of longer-acting pegylated CSFs in 
patients with myeloid leukemias, and they should not be used in 
such patients outside of clinical Trials. 
MDS 
Intermittent administration of CSF may be considered in a subset 
of patients with severe neutropenia and recurrent infection. 
ALL 
CSF administration is recommended after the completion of the 
initial first few days of chemotherapy of the initial induction or 
first postremission course, thus shortening the duration of 
neutropenia of < 1,000/mm3 by approximately 1 week.  
Acute leukemia in 
relapse 
CSF should be used judiciously, or not at all, in patients with 
refractory or relapsed myeloid leukemia since the expected 
benefit is only a few days of shortened neutropenia.  
Radiotherapy ± 
chemotherapy 
CSF should be avoided in patients receiving concomitant 
chemotherapy and radiation therapy, particularly involving the 
mediastinum. In the absence of chemotherapy, therapeutic use 
of CSF may be considered in patients receiving radiation therapy 
alone if prolonged delays secondary to neutropenia are 
expected.  
Older patients 
Prophylactic CSF for patients aged ≥ 65 years with lymphoma 
treated with curative chemotherapy (CHOP or more aggressive 
regimens) should be given to reduce the incidence of FN and 
infections.  
Pediatric patients 
As in adults, the use of G-CSF is reasonable for the primary 
prophylaxis of pediatric patients with a likelihood of FN. Similarly, 

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Setting/Indication 
Recommendation 
the use of G-CSF for secondary prophylaxis or for therapy 
should be limited to high-risk patients. However, the potential 
risk for secondary myeloid leukemia or myelodysplastic 
syndrome associated with G-CSF represents a concern in 
children with ALL whose prognosis is otherwise excellent. For 
these reasons, the specific use of G-CSF in children with ALL 
should be considered carefully.  
Comparative clinical 
activity of G-CSF and 
GM-CSF 
No guideline recommendation can be made regarding the 
equivalency of the two colony-stimulating agents. Further Trials 
are recommended to study the comparative clinical activity, 
toxicity, and cost-effectiveness of GCSF and GM-CSF.  
Treatment for radiation 
injury 
Current recommendations for the management of patients 
exposed to lethal doses of total-body radiotherapy, but not doses 
high enough to lead to certain death due to injury to other 
organs, includes the prompt administration of CSF or pegylated 
G-CSF.  
Abbreviations: CSF, colony-stimulating factors; FN, febrile neutropenia; PBPC, peripheral-
blood progenitor cell; AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; ALL, 
acute lymphocytic leukemia; CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; 
G-CSF, filgrastim; GM-CSF, sargramostim; pegylated G-CSF, pegfilgrastim. 
 
 
 
 
 

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APPENDIX F:  REVISED NATIONAL CANCER INSTITUTE COMMON 
TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (NCI CTCAE), VERSION 4.0 
(PUBLISHED 28 MAY 2009)  
Revised National Cancer Institute Common Terminology Criteria for Adverse Events (NCI 
CTCAE), version 4.0 (published 28 May 2009)  
The National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) Common 
Terminology Criteria for Adverse Events (CTCAE), version 4.0 can be viewed on-line at the 
following NCI web site:  
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf  

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APPENDIX G:  KARNOFSKY PERFORMANCE STATUS  
 

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APPENDIX H:  MEMO FOR DEXAMETHASONE DOSE REDUCTION WITH 
CONCOMITANT ADMINISTRATION OF FOSAPREPITANT 
The current protocol recommends the following prophylactic medication regimen: 
 
Aloxi (palonosetron) 0.25mg IV, Emend (fosaprepitant) 150 mg IV and dexamethasone 
20mg IV within 30 minutes prior to treatment on days 1 and 8, repeated every 21 days. 
Patients will continue oral antiemetic prophylaxis at home with ondansetron 8mg bid and 
dexamethasone 4mg bid for 2 days after chemotherapy.  
 
 Fosaprepitant is a moderate inhibitor of CYP3A4, resulting in an increased serum concentration 
of dexamethasone.  The dose of dexamethasone, especially on day 1 and day 8, must be 
decreased to account for the drug-drug interaction. 
 
Per EMEND® Prescribing Information for the 150mg (Single Dose Regimen of EMEND): 
 
EMEND for Injection 150 mg is administered intravenously on Day 1 only as an infusion over 
20-30 minutes initiated approximately 30 minutes prior to chemotherapy. No capsules of 
EMEND are administered on Days 2 and 3. EMEND for Injection should be administered in 
conjunction with a corticosteroid and a 5-HT3 antagonist as specified in Table 1.  
 
Table 1 
Recommended dosing (Single Dose Regimen of EMEND) for the prevention of 
nausea 
and vomiting associated with highly emetogenic cancer chemotherapy 
 
Day of Infusion 
Post Infusion 
Day 1 
Post Infusion 
Day 3 
Post Infusion 
Day 4 
EMEND 
150 mg 
intravenous 
none 
none 
none 
Dexamethasone* 
12 mg orally 
8 mg orally 
8 mg orally 
twice daily 
8 mg orally 
twice daily 
5-HT3 antagonist 
See the package 
insert for the 
selected 5-HT3 
antagonist for 
appropriate 
Dosing 
information. 
none 
none 
none 
* Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1 
and in the morning on Days 2 through 4. The dose of dexamethasone accounts for drug 
interactions. 
 
Due to similar bioavailability of oral and IV dexamethasone, the IV dexamethasone dose should 
be decreased to 12mg as recommended.  The protocol has already conservatively adjusted the 
dose of oral dexamethasone on days 2 and 3 of treatment to 4mg BID.   
 
Karen Ansaldo, PharmD, BCPS 
Virginia G. Piper Cancer Center Clinical Trials 
HonorHealth 
 

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APPENDIX I:  THE MD ANDERSON SYMPTOM INVENTORY GASTROINTESTINAL 
CANCER MODULE (MDASI-GI) (TO BE SUBMITTED SEPARATELY FROM 
PROTOCOL FOR IRB APPROVAL) 
 
MD Anderson Symptom Inventory (MDASI) modules augment the 19 core MDASI 
symptom and interference items with additional items identified as unique to a particular 
patient population. MDASI modules may be disease-specific, disease-site-specific, or 
treatment-specific. 
The MDASI gastrointestinal cancer module (MDASI-GI) is a site-specific module. Along 
with the core MDASI’s 13 symptom items and 6 interference items, the MDASI-GI also 
assesses 5 symptoms specific to gastrointestinal cancer:  
 
• 
Constipation 
• 
diarrhea or watery stools 
• 
difficulty swallowing 
• 
change in taste 
• 
feeling bloated 
 
MDASI-GI Features 
 
• 
Purpose: To assess the severity of multiple gastrointestinal cancer-related symptoms 
and the impact of these symptoms on daily functioning 
• 
Population: Patients with symptoms caused by gastrointestinal cancer and its treatment 
• 
Assessment areas: Severity of multiple symptoms and the impact of symptoms on daily 
functioning during the last 24 hours 
• 
Method: Self-report; paper-and-pencil form or tablet PC (self-administered or via 
interview), or telephone-based interactive voice response (IVR) system 
• 
Time required: Five minutes 
• 
Scoring: Please see the MDASI User's Guide 
• 
Reliability: Cronbach alpha reliability ranges from 0.80 to 0.87 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX J:  THE BRIEF PAIN INVENTORY (BPI) – SHORT FORM (TO BE SUBMITTED 
SEPARATELY FROM PROTOCOL FOR IRB APPROVAL) 
 
The Brief Pain Inventory (BPI) is available in two formats: the BPI short form, which is used for 
clinical trials and is the version used for the foreign-language translations; and the BPI long 
form, which contains additional descriptive items that may be clinically useful (for example, 
items that expand the possible descriptors of pain, such as burning, tingling, etc.). For brevity’s 
sake and for the patient’s ease of use, however, we recommend the short form of the BPI. 
 
In response to the US Food and Drug Administration (FDA) guidance for the pharmaceutical 
industry on the use of patient-reported outcome measures in medical product development to 
support labeling claims, we have prepared a BPI User's Guide to provide documentation of the 
BPI's development and psychometric properties. The information offered therein addresses the 
recommendations in the FDA guidance and establishes the BPI's adequacy as a measure to 
support medical product claims. 
 
BPI Features 
• 
Purpose: To assess the severity of pain and the impact of pain on daily functions 
• 
Population: Patients with pain from chronic diseases or conditions such as cancer, 
osteoarthritis and low back pain, or with pain from acute conditions such as 
postoperative pain 
• 
Assessment areas: Severity of pain, impact of pain on daily function, location of pain, 
pain medications and amount of pain relief in the past 24 hours or the past week 
• 
Responsiveness: Responds to both behavioral and pharmacological pain interventions 
• 
Method: Self-report or interview 
• 
Time required: Five minutes (short form), 10 minutes (long form) 
• 
Scoring: No scoring algorithm, but "worst pain" or the arithmetic mean of the four 
severity items can be used as measures of pain severity; the arithmetic mean of the 
seven interference items can be used as a measure of pain interference 
• 
Reliability: Cronbach alpha reliability ranges from 0.77 to 0.91 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX K:  Fecal Samples for 16S Gut Microbiome rRNA Analysis [Chaput et al 2017]  
The instructions below will be provided to each subject and will be submitted separately for 
review.  
 
Fecal Sample Collection Instructions (to be included in collection kit) 
 
You have been provided with a Commode Specimen Collection System.  The collection system 
includes three items: a specimen container, container lid, and container frame pictured below.  
Please follow the instructions below. 
 
                                                   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1. Assemble the container and frame, as pictured below. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2. Place the frame and container under the toilet seat and pushed the container all the way 
to the rear of the commode.  
3. Defecate into the container without allowing any urine into the container.  
4. Carefully retrieve the container from the commode and remove the frame. 
 
5. Place the lid on the container as pictured. 
 

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6. Write the date and time of collection under your assigned subject ID on the label affixed 
to the lid. Please do NOT write anything else on the lid or container.     
7. Place the specimen container inside the provided specimen bag. 
8. Store the specimen container in the provided specimen bag in a cool place, such as a 
refrigerator (at approximately 4 °C).   Sample can be transported in the car without need 
for ice packs as long as the car is air-conditioned.  If the car is not air-conditioned, 
please transport specimen on ice to keep cool. 
9. Return the sample to the clinic within 48-hours of collection. This should correspond with 
your next scheduled study visit. IMPORTANT: If you cannot return the collected sample 
within 48 hours of collection, please contact the study team to make arrangements for 
return of the sample.