Clinical trial NCT03033225
Conditions: Advanced Pancreatic Carcinoma Locally Advanced Pancreatic Carcinoma Metastatic Pancreatic Carcinoma Pancreatic Neoplasm Stage II Pancreatic Cancer AJCC v8 Stage III Pancreatic Cancer AJCC v8 Stage IV Pancreatic Cancer AJCC v8 Unresectable Pancreatic Carcinoma
Sponsor: Mayo Clinic
Start date: 2017-05-31; Completion date: 2023-09-20
Enrollment: 13 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial studies how well ultrasound-guided verteporfin photodynamic therapy works for the treatment of patients with solid pancreatic tumors that cannot be removed by surgery (unresectable) or pancreatic cancer that has spread to other places in the body (advanced). Photodynamic therapy is a type of laser device that is guided by ultrasound imaging and used in combination with the drug verteporfin that may be less invasive and as effective as current treatment methods for patients with pancreatic cancer.

Detailed description:
PRIMARY OBJECTIVE:

I. To show that endoscopic ultrasound (EUS)-guided photodynamic therapy (PDT) to the pancreas is effective at direct ablation of advanced or locally advanced and small volume metastatic pancreatic tumors in a multicenter setting.

SECONDARY OBJECTIVE:

I. To evaluate the predictability of tumor necrosis as a function of delivered energy, based on pre-PDT contrast computed tomography (CT) scans.

TERTIARY OBJECTIVE:

I. Evaluate the safety of chemotherapy given two days after PDT.

QUARTERNARY OBJECTIVE:

I. Demonstrate that cancer biomarkers in pre- versus (vs.) post-PDT are surrogate markers of response.

OUTLINE:

Patients receive verteporfin intravenously (IV) and undergo fluorescence imaging and after 60 minutes undergo EUS-guided PDT.

After completion of study treatment, patients are followed up at 14 days, and at 3, 6, and 12 months.

Arms: arm 1: Patients receive verteporfin IV and undergo fluorescence imaging and after 60 minutes undergo EUS-guided PDT.
Interventions: intervention 1: Endoscopic Ultrasound intervention 2: Fluorescence Imaging intervention 3: Photodynamic Therapy intervention 4: Quality-of-Life Assessment intervention 5: Questionnaire Administration intervention 6: Verteporfin
Intervention descriptions: intervention 1: Undergo EUS-guided PDT intervention 2: Undergo fluorescence imaging intervention 3: Undergo EUS-guided PDT intervention 4: Ancillary studies intervention 5: Ancillary studies intervention 6: Given IV

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
 16-001243 
 
 
Phase II Study of EUS-guided Verteporfin PDT in Solid 
Pancreatic Tumors (VERTPAC-02) 
 
 
NCT03033225 
 
 
Document Date: 05/05/2023 


Version 1 5 May 2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Phase II study of EUS-guided verteporfin PDT in solid pancreatic tumors (VERTPAC-02) 
Wellman Center for Photomedicine, Harvard Medical School 
Massachusetts General Hospital, Boston MA 
Mayo Clinic, Rochester MN 
Tayyaba Hasan, Ph.D. 
PI: Vinay Chandrasekhara, M.D. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Version 1 5 May 2023 
 
 
 
Table Of Contents: 
 
Title Page: 
 
 
 
 
 
 
 
 
 
 
Page 1 
Table of Contents: 
 
 
 
 
 
 
 
 
 
Page 2 
Summary of Project 2 Supplement:  
 
 
 
 
 
 
Page 3 
Specific Aims and Hypothesis: 
 
 
 
 
 
 
 
Page 4 
Research Strategy: 
 
 
 
 
 
 
 
 
 
Pages 5-11 
Protection of Human Subjects: 
 
 
 
 
 
 
 
Pages 12-22 
Bibliography:  
 
 
 
 
 
 
 
 
 
Pages 23-29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Version 1 5 May 2023 
 
 
 
SUMMARY OF PROJECT 2 SUPPLMENT (06/2015) 
 
The goal of project 2 is to transform the management of pancreatic cancer (PanCa), a devastating disease 
that is most often diagnosed in later stages, when curative therapies are unlikely. This strategy starts with 
a target of advanced or locally advanced pancreatic cancer (LAPC) with a phase II trial of photodynamic 
therapy (PDT) to evaluate local destruction of the tumor.  This is later followed by a combination therapy of PDT 
and MM398, as a secondary goal of treating metastatic disease.  This initial Phase II trial is the stepping stone 
towards the more needed combination therapy trial, which has the potential of seriously impacting long term 
survival of these patients. As such, we are proposing to expedite the Phase 2 by creation of a multi-
center trial, combining patients at the University College London Hospital with a new two 
sites in the Mayo Clinic Health System (Rochester, MN).  This approach should increase the 
recruitment rate, and lead to a faster completion, allowing earlier transition to the 
combination therapy trial, and also brings part of the study to the United States for 
evaluation here. This trial will utilize a minimally invasive approach of endoscopic ultrasound (EUS)-
guided PDT, with the goal for outpatient therapy with improved safety and healthcare costs. Together, the 
UCLH and Mayo clinic will establish, in a multicenter phase II study, the efficacy of EUS-PDT using 
verteporfin (benzoporphyrin, BPD) to ablate solid tumors of the pancreas. Clinical contrast CT-based 
treatment planning will be used to deliver patient-specific PDT in the trial as well, adding additional 
dosimetry innovation to the study. The study will recruit both localize advanced pancreatic cancer and 
metastatic disease, that will also establish the safety of giving chemotherapy almost immediately after PDT. 
The immediate impact of this project will be to improve the care of patients with PanCa, and more broadly 
the findings will establish a clinical framework to translate new nanomedicine and combination-based targeted 
therapeutic discoveries for cancer. 
 
 
 
Potential public health benefits: The clinical studies described above provide new minimally invasive 
treatment option aimed at improving the length and quality of life in patients with PanCa. Rapid control of 
local disease can help alleviate obstructive symptoms and increase tolerance to systemic therapy. 
The multi-center approach to the trial will bring the treatment to the United States for evaluation in our healthcare 
system, as well as expedite the results of the trial, to allow the eventual combination trial to be completed in a 
more efficient manner.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Version 1 5 May 2023 
 
 
 
 
 
 
 
 
SPECIFIC AIMS 
The overall aim of this supplement is to contribute to improved treatment of pancreatic tumors, using the 
minimally invasive technique of endoscopic ultrasound (EUS)-guided PDT and CT-based dosimetry as a 
predictive tool for treatment planning, which was shown to be a key element in this program project. The 
five-year survival of PanCa is less than 6% and this has remained unchanged over the last four decades. This 
work follows on from the PI, Dr,Pereira’s recently completed phase I clinical study of verteporfin PDT in 
patients with PanCa. In this dose escalation study, it was demonstrated that PDT can be delivered safely to 
patients with locally advanced cancers, with an increase in the diameter of necrosis with increasing light 
dose. The phase II proposed follow up will confirm that beyond safety, that PDT can yield good 
local control of pancreas disease. These studies will then inform the design of future studies of PDT + 
advanced chemotherapy combinations, as proposed in the last aim of the Project 2. The primary goal of this 
supplemental study is to assist the Phase 2 recruitment and trial by doubling the number of subjects that can be 
recruited, and power the study to assess 
 
 
Hypothesis 1: EUS-guided PDT will provide effective ablation of solid lesions of the pancreas 
(multi-center phase II clinical trial at UCL + Mayo). 
Clinical use of PDT for PanCa has been pioneered by the Project 2 group, and a positive correlation was 
established between delivered energy and the extent of tumor necrosis around interstitial fibers, with no 
serious adverse events. We aim to improve the approach by moving to a minimally invasive approach of 
EUS, in conjunction with dosimetry to monitor treatment (jointly with Project 4). 
 
Aim 1.  To participate in the conduct a phase II study of EUS-guided PDT in PanCa. PDT will be done initially 
at a single site with a fixed light dose for the first group of patients, then at multiple sites to match the 
zone of tumor necrosis to tumor volume. 
 
 
 
This work will lead into the next logical step in the trial, which was the major goal of Project 2, namely a 
combination therapy trial using PDT, standard chemotherapy and in patients with advanced or locally 
advanced and metastatic disease. The advanced cancer patients will be defined as patients with at least a 50% 
increase in tumor volume or new metastasis regardless of whether the patients had chemotherapy. All 
participants will be within ECOG performance status of 0-2.This work provides a direct bench-to-bedside 
translation, as we will use the most effective combination sequence form project 3 as they study in pre-clinical 
work. While this is not the goal of this current supplement, it is a future direction, which will be expedited by the 
completion of this proposed Phase II trial.  
 
After intravenous administration of verteporfin, fluorescence readings will be taken from the patient’s buccal 
mucosa to register the fluorescence peak. This is performed using a mobile fluorimeter that using an ipad as 
the processor. The device delivers a very small amount of light to the buccal mucosal and can measure 
nanogram levels of drugs. A gradient spectrophotometer is coupled to a CCD to record the fluorescence. 
Background fluorescence will be performed earlier in the day from the same area of buccal mucosa. The 
measurements will be taken every 10 minutes until the procedure (total 6-9 measurements). 
 
 
We plan to take FNA biopsies of the lymphocytes to assess immune response due to treatment. 
 


Version 1 5 May 2023 
 
 
Research Strategy 
a)  SIGNIFICANCE 
The goal of this project is to transform the management of pancreatic cancer (PanCa) in the advanced or 
locally advanced, and metastatic phases, using PDT in combination with systemic therapy. Specifically, we 
will build on o u r  previous phase I findings of PDT-induced tumor necrosis in PanCa patients that has been 
shown to be safe without significant toxicities, a n d  move to the minimally invasive approach of EUS-
guided PDT, with the potential for outpatient therapy with improved safety and healthcare costs. Prior 
studies in a mouse xenogaft model of pancreatic cancer at the Mayo Clinic also demonstrated the potential 
efficacy of next generation photosensitizers in photodynamic therapy. In particular, given that most pancreatic 
cancers consist of fibroblasts that encase tumor cells, it appears logically to have a locally delivered therapy which 
could potentiate additional chemotherapeutic agents. We will allow early delivery of chemotherapy 
after this therapy and observe if this can enhance the effectiveness of chemotherapy. 
Single therapies alone are ineffective in PanCa, it is hypothesized that this combination strategy will enhance 
survival of patients who have a d v a n c e d  o r  locally advanced and/or metastatic disease. We will also 
use EUS-PDT in patients with premalignant cystic neoplasms of the pancreas, which carry a significant 
risk of cancer development. 
 
 
a.1: Pancreatic Cancer 
Worldwide, PanCa is one of the top 10 leading causes of cancer deaths, and ranks fourth as a cause of cancer 
death in the UK and USA (1). Overall, the long term prognosis of the disease is poor with a one-year survival 
rate of no more than 10%. F o r  c an c e r s  s t ag e d m o r e  a d v a nce d  th a n  S ta g e  1 B ,  5  y e ar  s ur v i v a l 
i n  le s s  th a n  7% .  For non-metastatic disease, median survival is 6–10 months although for those with 
metastatic disease at presentation, survival is only 3–6 months (2, 3). While there have been small gains 
in therapeutic options for patients in recent years, there has been no significant improvement in overall 
outcome for more than two decades. Novel treatment strategies for advanced tumors and improved detection 
and ablation of premalignant lesions are necessary to improve outcome. 
 
According to the SEER (Surveillance, Epidemiology, and End Results Program) database, it is projected that 
there will be 48,760 new cases of pancreatic cancers in the United States (incidence of 10.4/100,000) with a five 
year projected survival rate of only 7.2%. The lifetime risk of developing pancreatic cancer is 1.5% in both men 
and women. There is also estimated to be 40,560 deaths due to pancreatic cancers in 2015. There has not been a 
major advancement in survival with unresectable pancreatic cancer that is the primary rationale for the 
development of new innovative therapies such as photodynamic therapy. 
 
a.2: Current treatment of pancreatic cancer 
In series from specialized centers, over 10% of patients may be resectable at presentation, but in larger 
population-based studies the number undergoing resection with curative intent may be as low as 3% (4, 5). 
Even after resection, median survival is only 10–20 months and no more than 5–20% of resected patients 
survive more than five years (6). Options available for the treatment of inoperable patients are largely limited 
to chemotherapy, radiotherapy, or some combination of the two. In both the US and Europe, gemcitabine is 
the most commonly used agent. The UK GemCap study - a phase III multicenter randomized clinical trial 
comparing gemcitabine alone or in combination with capecitabine for the treatment of 533 patients with 
advanced PanCa – reported a median survival in the combination capecitabine + gemcitabine group of 7.1 
months compared with 6.2 months in those who received gemcitabine alone, with 1-year overall survival 
rates of 24.3% vs 22% (HR = 0.86; P=0.077) (7). The French randomized study of  FOLFIRINOX  
(fluorouracil,  leucovorin,  irinotecan  and oxaliplatin) versus gemcitabine chemotherapy, showed a 
significantly improved survival in the FOLFIRINOX group (median 11.1 vs 6.8 months; hazard ratio [HR] = 
0.57; P<0.001)) (8). A phase III study  of  weekly intravenous albumin-bound paclitaxel (nab-paclitaxel) plus 
gemcitabine resulted in a significantly higher overall survival compared with gemcitabine monotherapy (8.5 
vs 6.7 months; HR = 0.72; P<0.001), with survival rates of 35% versus 22% at 1 year (9). Further studies 
into combination regimens are needed. Trials of biological agents such as VEGF inhibitors in advanced 
disease have been largely unsatisfactory (10). The Canadian phase III trial of gemcitabine with erlotinib (a 
small molecule EGFR inhibitor) compared to gemcitabine alone, showed a significantly improved overall 


Version 1 5 May 2023 
 
 
survival in the combination arm, albeit with a median survival of only 6.2 vs. 5.9 months (11). Overall, the 
long-term prognosis of the disease is poor. Given these dismal results,  surgical debulking or interstitial ablation 
has been investigated as a potential additional therapy in PanCa. In a recent systematic review comparing 
R2 resections to palliative bypass alone in the management of advanced pancreatic ductal adenocarcinoma 
(PDAC), a small non-significant survival advantage was observed in the R2 resection group; 8.2 months 
compared to 6.7 months in the palliative bypass group. However patients undergoing R2 resections had a 
significantly higher morbidity (RR: 1.75, 95% CI  1.35–2.26;  P<0.0001), mortality (RR: 2.98, 95% CI 1.31–
6.75; P=0.009) and a longer hospital stay (mean difference, 5 days; 95% CI 1–9 days; P=0.02), so that R2 
resections cannot be recommended as part of standard management (12). In considering better alternatives, 
minimally invasive  ablative  therapies  delivered  percutaneously  or endoscopically have become part of 
standard therapy in many other solid organ tumors, particularly in patients with inoperable disease or in 
patients unfit for surgical resection.(13) We therefore believe that for PanCa, a minimally invasive treatment 
capable of local destruction of tumor tissue with low morbidity may  have  an important place in the treatment 
of this disease. 
 
a.3. Future treatment: Advantages of Endoscopic versus Percutaneous delivery of PDT for 
PanCa 
PDT is a targeted anti-cancer treatment modality that has been extensively investigated in preclinical 
PanCa models by our group for mTHPC (14) and verteporfin (15) mediated PDT. These studies showed 
safety and efficacy in both normal tissues and transplanted tumors. We have also performed initial clinical 
studies of PDT for PanCa using mTHPC and CT-guided, percutaneous needle placement. Our group has showed 
feasibility, safety to surrounding normal tissues and successful induction of tumor necrosis; indicating that 
PDT was useful for local debulking of PanCa (16). These results motivated a Phase I clinical study using 
verteporfin-mediated PDT - chosen over mTHPC due to a reduced drug-light interval and photosensitivity 
times. We will develop a similar protocol for EUS-guided PDT of cystic tumors of the pancreas. Based on 
our own published experience with endoscopic PDT and EUS-FNA (17, 18), we expect EUS-PDT to be 
associated with a very low side effect profile and fewer complications than interstitial PDT or EUS-guided 
alcohol injection or radiofrequency ablation and will be an ideal therapy for those who are unfit for surgery 
or who have premalignant lesions who would otherwise require long-term surveillance. EUS-PDT represents 
a highly innovative approach towards 
day case anticancer therapy. 
 
Fig. 1. a) Light delivery after CT-
guided insertion of 
multiple 19G 
needles  into the pancreas under local 
anaesthetic 
and 
i.v. sedation. 
b) 
Endoscopic delivery of PDT under 
conscious sedation. 
 
a.5: Experimental Treatments for Locally Advanced Pancreatic Cancer at the Mayo Clinic 
 
The Mayo Clinic currently is the site of a Pancreatic Cancer SPORE headed by Gloria Petersen, PhD. The 
institution has been very active in the development of potential therapies for pancreatic cancer. Several recent 
studies have involved potential new therapeutic pathways. This includes a recently published study 
investigating the use of inhibitors of Nampt to decrease pancreatic cancer cell growth in vitro and in vivo 
animal models. This is a novel approach that targets the NAD salvage synthesis pathway and inhibition of 
Nampt was found to decrease lactate production, mitochondrial function, and ATP. In addition, CD38 which is 
an NADase was found to modulate this effect. Lowering the level of CD38 decreased the response of Nampt to 
inhibition which was a novel observation. This pathway might well enhance the effects of PDT on pancreatic 
cancer (57). Mayo Clinic researchers also recently published on the advantages of the combined effects of 
TRAIL and GSK-3 inhibitors on increasing apoptosis in pancreatic cancer cell lines resistant to apoptosis. 
These investigators found that overexpression of GSK-3B led to resistance to pro-apoptotic signaling from 
TNFa and TRAIL through anti-apoptotic genes such as Bcl-xL. This was reversed by inhibition of GSK-3B. 
These observations lend further rationale to the addition of GSK-3 inhibitors to TRAIL for therapy of 
pancreatic cancer (58). These are only a sample of the studies that have been developed through our Pancreatic 
Cancer Spore. 


Version 1 5 May 2023 
 
 
 
Efforts have also been made to characterize young onset pancreatic cancer in a study being conducted at the 
Mayo Clinic that is collecting genetic information on all patients with pancreatic cancer diagnosed earlier than 
age fifty. It is hoped that specific genetic patterns can be detected to determine if there are underlying 
mechanisms for these younger patients. This study is being conducted by Dr. Robert MacWilliams.  Novel 
therapies are also being investigated such as the use of immunotherapy in conjunction with stereotactic body 
radiation to treat locally advanced pancreatic cancer. Mayo Clinic is part of the Alliance for Clinical Trials in 
Oncology which consists of approximately 10,000 oncologist sponsored by the NCI. As part of these multi-
center trials, Mayo is involved studies using Abraxane and gemcitabine in local pancreatic cancer, Nivolumab 
with Abraxane and carboplatin in advanced pancreatic cancer, and rucaparib in patients with pancreatic cancer 
and a known BRCA mutation among several others. We also participate with the RTOG to investigate the 
effects of high or standard intensity radiation therapy in combination with chemotherapy. This wide variety of 
studies increases the likelihood of referrals to our institution for this novel protocol. Based on our past 
recruitment, the Mayo Clinic Rochester treats about 80 patients a year with locally advanced pancreatic cancer 
every year for the last 5 years. We believe that it would be reasonable to anticipate that we could recruit at least 
5 patients into this study each year. 
 
b. INNOVATION 
Key innovations in this proposal are: 
1. 
Development of the minimally invasive technique of EUS-guided PDT to provide effective, minimally 
invasive ablation of solid tumors of the pancreas (Phase II clinical trial). For patients choosing additional 
conventional chemotherapy, this will also provide the opportunity to assess the safety of giving 
chemotherapy in much closer time relationship to PDT than previously. 
2. 
Use of contrast-CT as a clinically implementable technique for optimizing the light dose to predict the 
extent of PDT necrosis and so match this to the extent of disease without causing any unacceptable damage 
to adjacent normal structures. 
3. 
Assessment of pancreatic tissue immediately preceding photoradiation to assess for verteporphyrin 
concentrations and potential biomarkers for response. 
  
b.1 EUS-guided PDT will enable effective ablation of solid tumors of the pancreas. 
Based on our c o l l a b o r a t o r s  a t  t h e  U n i v e r s i t y  C o l l e g e  L o n d o n ’ s  previous animal experimental 
work, and our pre-clinical and clinical trials of pancreatic PDT, a phase I study of verteporfin PDT in locally 
advanced unresectable PanCa (VERTPAC-01) was undertaken. In the initial dose escalation part of the study, 
patients were treated with verteporfin PDT to assess its general safety profile, to determine the optimum 
treatment parameters needed to achieve effective and safe necrosis of tumor, and to confirm safety of 
administration of subsequent conventional palliative chemotherapy. Inclusion criteria included a 
histopathological/cytological diagnosis of PanCa, unresectable, non-metastatic disease confirmed at 
multidisciplinary review and adequate biliary drainage (serum bilirubin < 2.5 x upper limit of normal). All 
patients received a dose of verteporfin 0.4 mg/kg bodyweight intravenously, followed by light activation 60 
minutes later under subdued lighting conditions. Treatment was via a single 10 mm tip diffuser fiber which 
was placed under CT guidance by an experienced radiologist (Figure 1). With increasing light doses, there was 
an increase in the extent of tumor necrosis around the fiber with no serious adverse events or reports of 
photosensitivity. This study aims to replicate these findings using the minimally invasive approach of EUS. 
Initially, only a single position of the laser fiber will be used, but in later patients multiple fiber positions will 
be used to show that it is possible to treat the full volume of appropriate cancers with endoscopic placement 
of the treatment fiber in more than one site. This is essential to show that endoscopic fiber placement can 
cover a comparable volume of tumor to the multi-fiber, percutaneous approach used in the previous studies. 
 
 
 
 
 
 


Version 1 5 May 2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fig. 2. Patient undergoing verteporfin PDT. The image on the left shows a baseline contrast-enhanced 
CT with a low attenuation mass in the head of the pancreas. The centre image shows percutaneous needle 
placement into the tumour. The image on the right shows the 
day 5 post PDT contrast-enhanced CT with a 2.67 cm3 zone of necrosis in the region of the pancreatic head. 
 
 
b.2: Use of contrast-CT to predict PDT response. 
 
As reported in Project 4 and Core C, retrospective analysis of our Vertpac data showed that the CT 
venous phase contrast enhancement (when compared with CT without contrast), a measure of the blood 
concentration around the target zone, was strongly correlated with the volume of necrosis per unit of 
li gh t energy deposited. This indicates that CT contrast should be a useful dose planning guide in future 
trials with photodynamic therapy. 
 
 
c. 
APPROACH 
c.1 
(Aim 1) Phase II study of EUS-guided verteporfin PDT in solid pancreatic tumors (VERTPAC-0
c.1.a 
Objectives 
Primary: To show that EUS-guided PDT to the pancreas is effective at 
direct ablation of a d v a n c e d  o r  locally advanced and small volume 
metastatic pancreatic tumors in a multicenter setting. 
Secondary: To evaluate the predictability of tumor necrosis as a function 
of delivered energy, based on pre-PDT contrast CT scans. 
Tertiary: Evaluate the safety of chemotherapy  given  two days after PDT 
Quarternary: Demonstrate that cancer biomarkers in pre- 
vs. post-PDT are surrogate markers of response. 
 
 
 
 
 
 
c.1.b 
Design of VERTPAC-02 study 
This will be a phase II study of 15 (UCL) + 15 (Mayo) patients with histologically proven a d v a n c e d  o r  
locally advanced PanCa or other solid tumors unsuitable for surgical resection. In the first 5+5 patients, 
EUS guided verteporfin PDT will be used with light delivered at just one site. In the following 10+10 
patients, light will be delivered with the fiber at multiple positions, as required to ensure treatment of all 
appropriate areas of the cancer, as was done in the previous studies with percutaneous fiber insertion. Each 
patient will be given verteporfin 0.4 mg/kg bodyweight intravenously, followed by light activation 60 minutes 
after photosensitization (acceptable treatment window 60- 90 minutes). Light delivery will take place via a 
5-20 mm length diffuser fiber placed under EUS guidance using red laser light at 690nm. The light dose 
delivered down the fiber will be fixed at 40 -80 J/cm, which was found to be optimum in our previous 
VERTPAC-01 study. All patients will be prescribed ciprofloxacin as a prophylactic to reduce the potential risk of 
infection associated with the fine needle puncture of the tumor. If a patient is allergic to ciprofloxacin, another 
acceptable broad spectrum antibiotic will be prescribed at the investigators discretion. 
Patients will be evaluated by contrast enhanced CT at 2 days after PDT (treatment day 3), and they 
will be able to commence conventional palliative chemotherapy after that if they so wish within a week 
of PDT. Patients will also have additional blood draws taken for biomarker analysis before, 
during, and after their treatment. In previous studies, it was a protocol requirement that chemotherapy 
Linear
 


Research Strategy 
Page 550 
Version 1 5 May 2023 
 
 
not be given within a month of PDT. However, PDT is a local, one off treatment and chemotherapy is 
systemic and ongoing. It is an important innovation to give chemotherapy much earlier after PDT as our 
previous study on PDT for biliary tract cancer showed that delay in giving chemotherapy after PDT put 
patients at a disadvantage. Treatment response and time to disease progression will be assessed by CT 
scans at three-monthly intervals, as part of usual practice. Thereafter, patients will continue to be followed 
up for survival data. Second line chemotherapy and/or re-treatment with verteporfin PDT for progressive 
disease will be at the discretion of the investigators. 
 
c.1.c 
Patient eligibility:  See Table 1. 
 
 
 
 
 Inclusion Criteria 
Exclusion Criteria 
Histological/cytological Dx of advanced or 
locally advanced or small volume metastatic 
PanCa or other solid pancreatic tumor that is 
not amenable to curative surgical resection, or 
the patient is unfit, or declines surgery 
For locally advanced patients, evidence of 
metastases other than lung or liver. For lung 
metastases, greater than three lesions and any 
lesions greater than 5cm are excluded. For 
advanced patients, any metastasis is 
acceptable for enrollment 
Age > 18 years 
Age < 18 yr; Porphyria; pregnant or breast-
feeding 
Measurable disease as defined by the Response 
Evaluation Criteria in Solid Tumors (RECIST) 
Locally advanced disease involving > 50% 
circumference of the duodenum or a major 
artery within the treatment area 
ECOG performance status 0, 1 or 2 
ECOG performance status 3 or 4 
Estimated life expectancy of at least 12 weeks 
Previous treatment with curative intent for 
current disease within the past two weeks (i.e. 
prior resection, radical radiotherapy or 
chemotherapy) 
Capable of giving written informed consent 
Any psychiatric disorder making reliable 
informed consent impossible 
Adequate biliary drainage (serum bilirubin < 
2.5 ULN), with no evidence of active 
uncontrolled infection (patients on antibiotics 
are eligible) 
A history of documented hemorrhagic 
diathesis or coagulopathy on therapeutic 
anticoagulation; History of prior or 
concomitant other malignancy that will 
interfere with the response evaluation 
Women of child-bearing potential with a 
negative pregnancy test (qualitative serum 
HCG) prior to study entry AND must be using 
an adequate contraception method, which 
must be continued for 1 week after PDT 
Any evidence of sever or uncontrolled systemic 
diseases or laboratory finding that in the view 
of the investigator makes it undesirable for the 
patient to participate in the trial 
 
Contrast allergy not amenable to treatment 
with steroids and antihistamines 
 


Version 1 5 May 2023 
 
 
 
Sample Size and Power Calculation 
We have previously shown that the above treatment parameters result in at least a 12 mm region of 
necrosis around percutaneously placed fibers in PanCa, which will be considered criteria for a positive 
response. If we observe 16 (out of 30) patients with a positive necrosis region response around at least 
one of the fibers inserted, this would indicate that the true response rate is at least 53% (with 90% power 
and assuming a 25% variance), which will be significantly higher than the known response rate of at most 
30% for palliative chemotherapy (50). 
   
c.1.d 
Pre and post procedure assessments:  See Table 2. 
 
 
Clinical and laboratory assessments will be repeated prior to discharge (anticipated at day 3). All patients 
will be followed up on day 14 then at three, six and 12 months. At each visit, clinical symptoms will be 
reviewed, and quality of life and laboratory assessments repeated. In patients in good general condition with 
evidence of residual tumor or local tumor progression on repeat CT, up to two further PDT treatments may 
be offered at a minimum of four week intervals. If patients are unable to return for follow up they will be 
contacted by phone to complete the QOL assessment, as well as asked if they have had adverse events, 
hospitalization related to disease or progression of disease. 
Criteria for early termination of the trial 
As in our previous trials in this application, a DSMB will monitor toxicity. A grade 3 or 4 toxicity rate of 
>30% would be considered unacceptable. Therefore, if ≥13 patients (out of 25) suffer a grade 3/4 toxic 
event, the DMEC would consider stopping the trial because the likelihood of this occurring by chance alone is 
0.02 (statistically significant at the 5% level) if the true toxicity rate were ≤30%. 
c.1.e 
Photosensitizer  protocol 
After diagnosis and entry criteria are confirmed, patients will receive intravenous verteporfin 0.4 mg/kg 
bodyweight, 60 minutes before laser activation. The drug-light interval will be recorded to the nearest minute 
in the case report forms, with an acceptable treatment window being 60-90 minutes. This allows for the  re- 
positioning of the fiber if multiple sites are to be treated. Patients will remain in subdued lighting on the ward 
for 24 hours after injection, followed by re-adaptation to indirect sunlight for increasing periods during the 
morning and late afternoon of the next day. Bright indoor light will be permitted after 24 hours and 
exposure to direct sunlight allowed after 48 hours. 
c.1.f 
EUS-guided PDT Light Treatment 
All laser procedures will be carried  out in accordance with  the local laser safety  rules as  specified by  
the hospital laser protection advisor. When the EUS needle has been confirmed to be correctly sited in the 
tumor under real-time EUS control, a diffuser fiber of appropriate length will be passed down to the tip of 


Version 1 5 May 2023 
 
 
the needle. Prior to use, the system will be calibrated to deliver 150 mW/cm along the length of each diffuser 
fiber, with the light dose delivered kept constant at 40 -80 J/cm. The illumination time is expected to be 
approximately 5 minutes based upon the linear irradiance and the target dose. After delivery of the planned 
light dose at each site, the needle and fiber will be removed. 
c.1.g 
Dosimetry Studies: PS fluorescence and CT Perfusion 
Two levels of dosimetry will be completed in this patient group. Initially we will complete PS dosimetry 
by placement of a bare tip fiber down the EUS guided needle, immediately prior to the treatment fiber 
placement. Fluorescence measurements will be completed with the Dartmouth Dosimeter system, 
measurements being taken at several points across the lesion. Data from the phase 1 trial was inconclusive 
about the value of this approach, because of high variability in placement, through the percutaneous needles 
used. The EUS needle placement is likely to be more convenient for sampling at more sites and to assess 
repeatability of multiple placements of the fiber, although patients will only have one EUS examination 
when they are photosensitised. We will also study the correlation between the PS fluorescence level seen 
and the perfusion (as measured by CT contrast) observed at the fiber location. 
In the phase 1 trial, a strong correlation was seen between the volume of necrosis normalized by the 
light dose delivered, and CT contrast enhancement seen. We need to confirm this observation in the phase 
2 trial when all subjects are receiving the same light dose. Thus, pre-treatment CT scans ± contrast will be 
acquired and used for all subjects recruited into this trial. Following analysis of these data, if the strong 
correlation is confirmed, we will then be able to recommend adjusting light delivery to modulate the 
anticipated volume of necrosis in future patient studies.  Additionally, Project 4 is analysing this in the rabbit 
pancreas tumor model. 
c.1.h 
Treatment  Evaluation 
PRIMARY Response evaluation 
• 
Contrast-enhanced CT scans of the pancreas will be  evaluated  before  treatment and  on  day  3  (after 
treatment on day 1), for measurement of tumor volume using RECIST criteria and to assess the extent 
of tumor necrosis after treatment. 
SECONDARY Response evaluation 
• 
Progression-free survival will be determined at 6 months follow-up and beyond. 
• 
CEA and/or CA19.9 4-weekly if elevated prior to therapy 
• 
ECOG performance status and Brief Pain Inventory pain scores, prior to therapy and at follow-ups 
• 
Comparison will be made between the documented extent of necrosis and both the measured 
photosensitizer concentration, as assessed by fluorescence, and the estimated necrosis volume based on 
CT with and without contrast. 
c.1.i 
Monitoring of serum biomarker expression pre- and post- treatment 
Using different proteomic technologies we have identified several novel serum biomarkers which in 
combination with CA19-9 improve classification and lead time for detecting PanCa (unpublished and 
O’Brien, manuscript submitted to Gut). This work has used samples from diagnosed PanCa cases and 
relevant controls (biliary obstruction, chronic pancreatitis) and those taken up to 6 years prior to diagnosis 
from women enrolled onto the world’s largest ever RCT, the United Kingdom Collaborative Trial of Ovarian 
Cancer Screening.  We have identified several late markers (CA125, LRG1, CEA, MUC5AC) that are able to 
detect cancer in CA19-9-negative cases with several others showing detectable changes at least 12 months 
prior to the diagnosis (TIE2, vWF, AGR2). Marker panels combining these analytes are currently being 
validated for early detection using independent samples sets and we will next test them as predictive markers. 
We will examine modulations of these biomarkers in patients’ serum pre- and post-verteporfin PDT using 
established ELISA assays. Assays will be carried out on all patient samples prior to, immediately following 
(Day 2/3), 14 days and 3 months post- 
therapy. These will be correlated to clinical response to define surrogate markers of  outcome that can be 
translated to future trials if effective in predicting response. Samples will also be retained for future 
studies aimed at proteomics-based discovery work in which we have considerable expertise (51). During the 
placement of the fibers, suction will be applied and an aspirate will be collected to examine the tissue present for 
verteporphyrin concentration and for the presence of fibroblast markers of activation (alpha-Smooth Muscle 
Actin, vimentin) to determine if this has an effect on PDT response. 


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6. 
PROTECTION OF HUMAN SUBJECTS 
 
6.1. 
Risks to the subjects 
 
6.1.1. 
Human Subjects Involvement and Characteristics 
 
Patient Data Registration and Collection 
If confirmed as eligible for a particular trial, the patient will be allocated a unique trial number and the 
treatment regimen defined. All study data will be recorded on case report  forms  at  University  College  Hospital 
and Mayo Clinic.  All research staff who enter data onto the case report form will have signed the study 
signature and delegation of duties log before undertaking data entry. 
A password-protected, computer-based electronic database record of the study will be kept to facilitate 
statistical analysis. The study will be registered with the UCL data protection officer and comply with the 
Data Protection Act 1988. In addition, the study will be approved by the Mayo Clinic IRB and all 
records held in compliance with HIPPA requirements. Trial notes and source documents may be 
reviewed by the sponsor as part of internal audit or inspected by the regulatory authorities. 
 
Subject selection 
If confirmed as eligible, the patient will be consented and allocated a unique trial number and the 
treatment regimen defined. Ethnicity data will be collected. All study data will be recorded on case report forms. 
All research staff who enter data onto the CRF will have signed the study signature and delegation of 
duties log before undertaking data entry. 
 
Withdrawal of Patients 
When consenting to a particular trial, patients are consenting to trial treatment, trial follow-up and data 
collection. If a patient is withdrawn from trial treatment, follow-up and data collection will continue as 
per protocol. If the patient explicitly states their wish not to contribute further data to the study, the trial 
center should be informed in writing (letter or e-mail). Patients may be withdrawn from treatment for 
the following reasons: 
 
Patient withdraws consent 
Any change in the patient’s condition which justifies the discontinuation of treatment in the clinician’s 
opinion, e.g., progression, toxicity or intercurrent illness 
 
Laser safety 
The laser to be used will be a Opad L 690 nm, 0.3W Diode Laser or an OEM laser of similar specifications with 
1% power stability . As this laser was not designed for clinical use the following extra safety measures will be 
adhered to above those required for routine clinical use: 1) As the laser can emit light even when no fiber is 
attached, a sign will be placed onto the machine warning operators to never look into the aperture, 2) A stop 
watch will be used to time the duration of light delivery, 3) The power output will be calibrated using a 
power meter. The laser will be approved for electrical safety by the hospital engineering department. This is the 
same laser parameters previously used at the University College London for the initial studies. 
 
Photosensitizer  protocol 
Verteporfin (benzoporphyrin derivative monoacid ring A, BPD-MA; VisudyneTM) is licensed in the UK for 
treatment of age-related macular degeneration and will be purchased from Novartis Pharmaceuticals UK 
Ltd (Surrey, UK) as a lyophilized lipid-formulated powder and stored in the Pharmacy department at UCLH. 
Investigational medicinal product (IMP) dispensing will be the responsibility of the clinical trial pharmacist 
at UCLH and dispensing records will be maintained in pharmacy. In the United States, Visuadyne is 
available from Bausch and Lomb (Bridgewater, New Jersey) and will be stored in the Mayo Clinic 
Research Pharmacy at the Saint Marys Campus of the Mayo Hospital. Labeling of drug will be carried 
out by pharmacy and include the term ‘for investigational use only’. The lyophilized lipid-formulated powder 
will be mixed with distilled water to a final concentration of 2 mg/ml (previously referred to as liposomal 
formulation) by the chief investigator or appropriate members of his team. Investigational medical product 
(IMP) accountability will be the responsibility of the chief investigator. The dose, time of injection, lot 


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number and expiry date of the IMP will be recorded in the case report form. 
 
Non-study  Treatments 
Patients may receive all concomitant therapy deemed to provide adequate supportive care at the 
investigator’s discretion. All such medications or  other treatments taken by the patient during the study 
(including those initiated prior to the start of the study) will be recorded in the patient’s clinical notes 
and on the study case


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report forms. No immunotherapy, hormonal therapy (excluding contraceptives and replacement steroids), 
or experimental medications will be permitted for three days post-phototherapy . Any disease progression 
requiring other forms of specific anti-tumor therapy will be a cause for early discontinuation in the study. 
 
Discontinuation of therapy 
A patient will discontinue a study under the following circumstances: (i) If the physician thinks it would be 
in the best interests of the patient, (ii) If the patient requests discontinuation, or (iii) If unacceptable toxicity 
is seen. 
 
6.1.2. 
Sources of Materials 
Data to be recorded from patient interviews and medical records will consist of historical data and 
laboratory values necessary for the care of the patient, that impact upon potential response to PDT therapy, 
including the patient's current and prior biopsy results (histological tumor type) and any laboratory values 
pertaining to the patient's overall health status. 
Patient-specific Linkage/Subject I.D.: The patients' files will be coded by an ID number, maintained in a 
confidential location. Access to the data will only be possible by the Principal Investigator and by a small 
number of study personnel who will maintain confidentiality at all times. 
 
6.1.3. 
Potential Risks 
 
Risks and Guidelines for the Prevention of Toxicity 
The major side effect of PDT is photosensitization. All patients who receive verteporfin will be photosensitive 
and will remain, for three to four days after injection, in subdued lighting. Bright indoor light will be 
permitted after the initial four day period, but patients must observe precautions to avoid exposure of the 
eyes and skin to direct sunlight for at least 3 days. Patients who receive verteporfin can be safely exposed to 
sunlight only two days after sensitization. The level of phototoxicity will vary for different areas of the 
body, depending on the extent of previous exposure to light. Before exposing any area of skin to direct 
sunlight or bright indoor light, the patient should test it for residual  phototoxicity. A small area of skin 
should be exposed to sunlight for 10 minutes. If no phototoxicity reaction (erythema, edema, blistering) 
occurs within 24 hours, the patient can gradually resume normal outdoor activities, initially continuing to 
exercise caution and gradually allowing increased exposure. If a phototoxicity reaction occurs with the limited 
skin test, the patient should continue the existing precautions for another week before re-testing. As the 
tissue around the eyes may be more sensitive, it is not recommended that the face be used for testing. If a 
patient travels to a different geographical area with greater sunshine, they should retest their skin for 
phototoxicity. Ultraviolet (UV) sunscreens are of no value in protecting against phototoxicity reactions because 
photoactivation is caused by visible light. Ocular discomfort, commonly described as sensitivity to sun, bright 
lights, or car headlights, has also been reported in patients. For 30 days following treatment, patients 
should wear dark sunglasses when outdoors, and should consult their ophthalmologist if they notice any 
change in vision after treatment. All patients will be given information on barrier protection (hat, gloves, 
long sleeves etc) and an emergency 
contact number will be given for patients and GPs. Similar precautions will be taken with verteporfin for a 
48 hour period. 
 
6.2. 
ADEQUACY OF PROTECTION AGAINST RISKS 
 
6.2.1. 
Recruitment and Informed Consent 
Written informed consent will be obtained from all patients  according to the UCLH guidelines  ‘Consent for 
research on human subjects’ or according to Human Subjects guidelines from the Mayo Clinic 
Institutional review board. The Investigator is required to explain the nature and purpose of the study 
to the patient prior to study entry. Consent to enter a particular trial must be sought from each patient or 
their legal representative only after a full explanation has been given, an information leaflet offered and 
time allowed for consideration. Signed patient consent should be obtained. The right of the patient to refuse 
to participate without giving reasons must be respected. When agreed by both parties, the patient will sign 
a consent form and be provided with a copy. One copy will be placed in the medical notes and the consent 
process documented. Consent will be obtained by the chief or one of the principal investigators. After the 


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patient has entered the trial the clinician will remain free to offer alternative treatment to that specified 
in the protocol at any stage, if he/she feels it is in the patient’s best interest, but the reasons for doing. so 
should be recorded. In these cases the patients remain within the study for the purposes of follow-up and 
data analysis. All patients are free to withdraw at any time from the protocol treatment without giving 
reasons and without prejudicing further treatment. 
 
 
 


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6.2.2. 
Protection Against Risk 
 
Adverse Events (Definitions) 
An Adverse Event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product regardless of the causal relationship with this treatment. 
Any adverse event or concurrent illness experienced by a patient during any portion of the study will be 
described in detail, fully evaluated and recorded on an adverse event form in the case report form by the 
investigator. 
An Unexpected Adverse Event is defined as an adverse drug event the nature or incidence of which is not 
consistent with applicable product information. 
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that at any drug dose 
results in: 
• 
Death 
• 
Inpatient hospitalization or prolongation of hospitalization 
• 
A life-threatening event 
• 
Severe or permanent disability 
• 
Cancer (other than cancers diagnosed prior to enrolment in studies involving patients with 
cancer) 
• 
Congenital anomaly 
 
Note that as defined above, serious events, expected or not, are not necessarily causally associated with the 
study treatment. Those occurring during treatment and up to one month post-treatment will  be  reported 
promptly, and if assessed as a Suspected Unexpected Serious Adverse Reaction (SUSAR) within the 
timeframes (as specified in the Clinical Trials Regulations 2004) will be reported promptly to the 
appropriate authorities including the independent Data Monitoring and Ethics Committee (DMEC, see 
Section 5 below). The ultimate decision for the continuation of the trial lies with the DMEC. 
 
All adverse effects will  be assessed for the following: 
• 
Severity (according to NCI toxicity criteria) 
• 
Causality 
• 
Expectedness (see below) 
• 
Seriousness (see above) 
 
Expected adverse events 
• 
Related to the photosensitiser 
• 
Photosensitivity 
• 
Infusion related pain 
• 
Vasovagal reaction 
• 
Hypersensitivity  reaction 
• 
Related to percutaneously delivered photodynamic therapy 
• 
Abdominal pain 
• 
Nausea and vomiting 
• 
Pancreatitis 
• 
Bleeding 
• 
Ileus 
• 
Related to cancer progression 
• 
Jaundice 
• 
Anorexia and weight loss 
• 
Cholangitis 
• 
Duodenal obstruction 
• 
Growth and metastasis of tumor 
 
Pre-existing medical conditions 


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Any medical conditions present at baseline, which worsen after exposure to a study treatment,  must  be 
assessed and recorded as an AE on the adverse event form of the case report form. 
 
Treatment-emergent adverse events 
A treatment–emergent adverse event (TEAE) is defined as any event not present prior to exposure to 
study medication or any event that worsens in duration, intensity or frequency following exposure to study 
medication. The adverse event form of the case report form will be completed for all TEAEs. 
Part of the adverse event documentation will involve the investigator making a drug related assessment. 
To promote consistency between investigators, the following elements should be taken into consideration 
along with good clinical judgment when determining the relationship of study medication to adverse event. 
Existence of a temporal relationship between the event and the use of  the study medication Ablation of the 
event when the study medication is withdrawn 
Reappearance or worsening of the event when the study medication is re-administered 
Previous experience with the study medication or related compounds 
Influence of a pre-existing condition, concomitant disease or medication, or other environmental factors 
The number of elements met and good clinical judgment should be used as a guide for determining the 
drug-related assessment. A binary assessment scale will be used to assess causality 
 
Laboratory  abnormalities 
During the course of the study the investigator will be required to comment on any laboratory values 
outside the reference range. A laboratory abnormality will be regarded as an AE and recorded on the 
adverse event form of the case report form if according to the investigators judgment the value is 
significantly worse than at pre-treatment (significantly worse is defined by grade 3 or 4 by the NCI Toxicity 
criteria, version 3). 
 
Assessment of trial safety 
Annually the sponsor will provide the main REC and the MHRA with an annual safety report (ASR). The ASR 
will be prepared, using the sponsor’s ASR form, by the Chief investigator or a delegated PI, reviewed by the 
sponsor and when necessary, be referred to an independent committee (independent to the trial) such as 
the safety committee. This will be done in accordance with the sponsor’s SOP. 
 
6.3. 
POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO THE SUBJECTS AND 
OTHERS 
The patient will be counseled that he/she will not necessarily benefit directly from participation in this 
study. However, the possibility exists that such participation in the study will help to develop improved 
knowledge about the treatment of pancreatic cancer. 
 
6.4. 
IMPORTANCE OF THE KNOWLEDGE TO BE GAINED 
The human studies described in Aims 1 and 2 of this research project may provide knowledge and techniques 
that lead to a form of treatment that significantly improves the length and/or quality of life for patients 
with pancreatic carcinoma, who currently have a dismal prognosis.  
 
6.5. 
DATA AND SAFETY MONITORING PLAN 
 
Data Monitoring and Ethics Committee (equivalent to Data & Safety Monitoring Committee 
in US) 
The role of the Data Monitoring and Ethics Committee (DMEC) o r  t h e  D a t a  a n d  S a f e t y  
M o n i t o r i n g  b o a r d  ( D S M B )  is to provide independent oversight on the safety aspects of the trial. 
The DMEC will also determine the frequency and types of analyses. The committee will meet quarterly to 
review the data on safety and provide direction  on  whether  a  particular  trial  should continue or be stopped. 
Upon review of the data, the DMEC or DMSB committee has the power to recommend changes in the 
experimental protocol, which would additionally be reviewed, or to halt the trial pending further 
investigation of the data. Halting a trial will trigger an investigation by the Main REC and Sponsor, and the 
results of the investigation will be reported to the DMEC, TSC, the MHRA and the relevant pharmaceutical 


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company. A Data Safety Monitoring Committee will also be established at Mayo Clinic Rochester to monitor the 
study. Should an adverse event occur, it will be reported to both the DMEC and DSMB simultaneously. Should 
there be any disagreement on a course of action, the most conservative approach with the greatest safety for 
patients will be followed. (ie perform any recommended diagnostic studies and continue to observe the patient 
for the longest period recommended)  
 
Trial Management Group 


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For each of the trials, a Trial Management Group led by the Chief Investigator (Dr Pereira) `will be 
responsible for overseeing the study. The Trial Management Group will agree protocol amendments prior to 
submission to Main REC and LREC.  All investigators will be kept informed of important amendments. 
 
Trial Center 
The UCL/UCLH & RFH Joint Research Office (JRO) will be responsible for the day-to-day management 
of study D.1 and may also be approached to run the other studies. UCL will act as custodian of the data. 
The Trial Center will apply for Main REC approval. In addition, the Trial Center will ensure that all 
SAEs and SUSARs are appropriately reported to the relevant pharmaceutical company, Main REC and 
the MHRA, as well as to individual investigators. For Mayo Clinic patients, all serious complications or trial 
violations will be reported to the IRB of the Mayo Clinic as well as the RFH JRO. 
 
Investigators  Responsibilities 
Individual investigators will have research ethics committee approval for all procedures upon initiation of 
each trial, and once approved they recruit patients, adhere to the most recent version of the protocol 
(taking into account any updated safety information and protocol amendments), conduct of the study, 
collect the data on the CRFs and prompt notification of adverse events. Investigators should refer SAEs 
as required by their research ethics committee. An agreement between the site and the Trial Center will 
be signed at the start of the trial. 
 
Ethics Approval 
The Trial Center will obtain approval from the Main UK Research Ethics Committee. The trial protocol must 
be submitted to each participating hospital’s Local Research Ethics Committee (LREC).  The  Trial Center will 
require notification of favorable Site Specific Assessment before accepting patients into the trial. In addition, 
the Mayo Clinic IRB will approve this study. 
 
Governance 
Each study will be conducted in accordance with the recommendations for physicians involved in research 
on human subjects adopted by the 18th World Medical Assembly, Helsinki 1964 and later revisions, as well 
as the ICH Good Clinical Practice guidelines, the Medicines for Human Use (Clinical Trials) Regulations 2004 
and the Research Governance Framework for Health and Social Care April 2005. 
 
Regulatory issues 
The trials will be reviewed by the Medicines and Healthcare products Regulatory Agency (MHRA) and 
authorization to conduct the trial will be received prior to commencement. Each trial will receive a Clinical 
Trials Authorization from the MHRA. The trials will be run to MRC/ICH Good Clinical Practice guidelines 
in accordance with the EU directive and in accordance with ICH GCP in non-EU countries. In the United 
States, approval will be sought from the institution IRB. All studies at the Mayo Clinic will be conducted in 
accordance with Good Clinical Practice Guidelines as well. 
 
Audits & Inspection 
The study may be subject to inspection and audit by the UCL/UCLH Joint Research Unit and other 
regulatory bodies, such as the MHRA, to ensure adherence to Medicines for Human Use (clinical trials) 
regulations 2004 (SI 2004/1031). 
 
Sponsorship 
Single center trials will be sponsored jointly by UCLH and UCL while multicenter trials will be sponsored 
by UCL. UCL will provide non negligent indemnity for the trial and negligent cover will be provided 
through the normal NHS mechanisms. UCLH/UCL will undertake adequate and appropriate monitoring of 
the trial to ensure compliance with applicable regulatory standards.  The trial documentation and data may 
also be  subject to internal auditing by UCLH/UCL. 
 
6.1.6.   ClinicalTrials.gov REGISTRATION REQUIREMENTS 
Each of the studies (Aims 1, 2 and 3) will be registered at the ClinicalTrials.gov website, in the interest 
of sharing information with interested parties. 


Women & Minorities Inclusion 
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Inclusion of Women and Minorities 
 
Women and minorities will be included in all trials, and entered into the trial based upon the population 
base at the institutions where the trial is being performed.  Our estimates in the Targeted/Planned 
Enrollment Table are designed to reflect our local population base. 
Children will not be included in this study as pancreatic cancer is extremely rare in children.


Contact PD/PI: Hasan, Tayyaba 
Project-002 (885) 
OMB Number: 0925-0002 
Page 567 
Funding Opportunity Number: PAR-13-321. Received Date: 2014-02-10T11:49:46.000-05:00 
Tracking Number: GRANT11577874 
 
 
 
 
Planned Enrollment Report 
 
 
 
Study Title: 
Phase II study of EUS-guided verteporfin PDT in solid pancreatic tumors (VERTPAC-02) 
 
Domestic/Foreign: 
Domestic 
 
Comments:  
 
 
Additional recruitments only shown here in addition to the 25 at UCLH 
 
 
Racial Categories 
Ethnic Categories 
 
Total 
Not Hispanic or Latino 
Hispanic or Latino 
Female 
Male 
Female 
Male 
 
American Indian/Alaska Native 
 
0 
 
0 
 
0 
 
0 
 
0 
 
Asian 
 
0 
 
0 
 
0 
 
0 
 
6 
 
Native Hawaiian or Other Pacific 
I l
d
 
0 
 
0 
 
0 
 
0 
 
0 
 
Black or African American 
 
1
 
1
 
0 
 
0 
 
2
 
White 
 
14 
 
14 
 
0 
 
0 
 
28
 
More than One Race 
 
0 
 
0 
 
0 
 
0 
 
0 
 
Total 
 
15
 
13
 
0 
 
0 
 
30
 
Study 2 of 3 


Contact PD/PI: Hasan, Tayyaba 
Project-002 (885) 
Inclusion Of Children 
Page 570 
 
 
 
 
 
 
Inclusion of Children 
 
Cystic and solid tumors of the pancreas are overwhelmingly diseases of older adults, and our IRB 
applications for the studies will exclude individuals less than 18 years old. However, we would not want to 
preclude the participation of a young patient if they felt highly motivated and are able to give informed 
consent in the presence of a parent or guardian. In the unlikely event we have a person under the age of 18 
eligible for one of the studies, we will write to the ethical committee requesting entry on compassionate 
grounds or exceptional circumstances. 


Contact PD/PI: Hasan, Tayyaba 
Project-002 (885) 
References Cited 
Page 571 
 
 
 
 
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Contact PD/PI: Hasan, Tayyaba 
Project-002 (885) 
References Cited 
Page 572 
 
 
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Contact PD/PI: Hasan, Tayyaba 
Project-002 (885) 
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15. 
Ayaru L, Wittmann J, Macrobert AJ, Novelli M, Bown SG, Pereira SP. Photodynamic therapy using 
verteporfin photosensitization in the pancreas and surrounding tissues in the Syrian golden hamster. 
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PubMed PMID: 17449962. 
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Bown SG, Rogowska AZ, Whitelaw DE, Lees WR, Lovat LB, Ripley P, Jones L, Wyld P, Gillams A, 
Hatfield AW. Photodynamic therapy for cancer of the pancreas. Gut. 2002;50(4):549-57. Epub 2002/03/13. 
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Wittmann J, Kocjan G, Sgouros SN, Deheragoda M, Pereira SP. Endoscopic ultrasound-guided tissue 
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18. 
Aithal GP, Anagnostopoulos GK, Tam W, Dean J, Zaitoun A, Kocjan G, Ragunath K, Pereira SP. 
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Laffan TA, Horton KM, Klein AP, Berlanstein B, Siegelman SS, Kawamoto S, Johnson PT, Fishman 
EK, Hruban RH. Prevalence of unsuspected pancreatic cysts on MDCT. AJR Am J Roentgenol. 
2008;191(3):802-7. Epub 2008/08/22. doi: 191/3/802 [pii] 10.2214/AJR.07.3340. PubMed PMID: 
18716113; 
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Spinelli KS, Fromwiller TE, Daniel RA, Kiely JM, Nakeeb A, Komorowski RA, Wilson SD, Pitt HA. 
Cystic pancreatic neoplasms: observe or operate. Ann Surg. 2004;239(5):651-7;  discussion  7-9.  Epub 
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PMC1356273. 
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Lee KS, Sekhar A, Rofsky NM, Pedrosa I. Prevalence of incidental pancreatic cysts in the adult 
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22. 
Lee LS, Clancy T, Kadiyala V, Suleiman S, Conwell DL. Interdisciplinary management of cystic 
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Le H, Ziogas A, Rhee JM, Lee JG, Lipkin SM, Zell JA. A population-based,  descriptive  analysis  of 
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Tanaka M, Fernandez-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, 
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Khashab MA, Shin EJ, Amateau S, Canto MI, Hruban RH, Fishman EK, Cameron JL, Edil BH, 
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ICF_001.pdf: 
 
 
 
 
 
 16-001243 
 
 
Phase II Study of EUS-guided Verteporfin PDT in Solid 
Pancreatic Tumors (VERTPAC-02) 
 
 
NCT03033225 
 
 
Document Date: 05/05/2023 


 
 
Approval Date:  
May 5, 2023 
Not to be used after: October 18, 2023 
 
IRB#: 16-001243 01 
Page 1 of 13 
IRB Doc. Ctrl # 10013.27 
 
 
 
 
 
 
 
 
Name and Clinic Number 
 
RESEARCH PARTICIPANT CONSENT AND PRIVACY 
AUTHORIZATION FORM 
 
Study Title:  Phase II study of EUS-guided verteporfin PDT in solid pancreatic tumors 
(VERTPAC-02) 
 
IRB#: 16-001243  
 
Principal Investigator: Dr. Vinay Chandrasekhara, MD and Colleagues 
 
Please read this information carefully. It tells you important things about this research study. A 
member of our research team will talk to you about taking part in this research study.  If you 
have questions at any time, please ask us. 
 
Take your time to decide.  Feel free to discuss the study with your family, friends, and healthcare 
provider before you make your decision.   
 
To help you decide if you want to take part in this study, you should know: 
• Taking part in this study is completely voluntary.  
• You can choose not to participate.  
• You are free to change your mind at any time if you choose to participate.   
• Your decision won’t cause any penalties or loss of benefits to which you’re otherwise 
entitled. 
• Your decision won’t change the access to medical care you get at Mayo Clinic now or in 
the future if you choose not to participate or discontinue your participation.   
 
For purposes of this form, Mayo Clinic refers to Mayo Clinic in Arizona, Florida and Rochester, 
Minnesota; Mayo Clinic Health System; and all owned and affiliated clinics, hospitals, and 
entities. 
 
If you decide to take part in this research study, you will sign this consent form to show that you 
want to take part. We will give you a copy of this form to keep. A copy of this form will be put 
in your medical record. 
 
 


 
 
Approval Date:  
May 5, 2023 
Not to be used after: October 18, 2023 
 
IRB#: 16-001243 01 
Page 2 of 13 
IRB Doc. Ctrl # 10013.27 
 
 
 
 
 
 
 
 
Name and Clinic Number 
 
CONTACT INFORMATION 
 
You can contact … 
At … 
If you have questions about … 
Principal Investigators: 
Rochester 
Dr. Vinay Chandrasekhara, MD 
 
Study Team Contact: 
Rochester: Kevin Buller 
 
 
 
Florida 
Herbert Wolfsen MD 
 
Florida 
Betsy Cayer CCRP 
Phone: (507) 284-2687 
 
 
 
Phone: (507) 255-5476 
Address:  
Mayo Clinic Rochester 
200 First St SW 
Rochester MN 55905 
 
Phone: (904) 953-6319   
 
Phone: (904) 953-7778 
 
Address:  
Mayo Clinic Florida  
4500 San Pablo Road, 
Jacksonville, FL 32224 
 Study tests and procedures 
 Research-related injuries or 
emergencies 
 Any research-related concerns or 
complaints 
 Withdrawing from the research 
study 
 Materials you receive 
 Research-related appointments 
Mayo Clinic Institutional 
Review Board (IRB) 
Phone:(507) 266-4000 
Toll-Free:(866) 273-4681 
 Rights of a research participant 
 
Research Participant 
Advocate (RPA) 
(The RPA is independent of 
the Study Team)  
 
Phone: (507) 266-9372 
 
Toll-Free: (866) 273-4681 
 
E-mail: 
researchparticipiantadvocate@
mayo.edu 
 
 Rights of a research participant 
 Any research-related concerns or 
complaints 
 Use of your Protected Health 
Information 
 Stopping your authorization to use 
your Protected Health Information 
Patient Account Services 
Toll Free:  
(844) 217-9591 
 Billing or insurance related to this 
research study 
 
Other Information:  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Website will not include information that can identify you. At most, the 
Website will include a summary of the results. You can search this Website at any time. 


 
 
Approval Date:  
May 5, 2023 
Not to be used after: October 18, 2023 
 
IRB#: 16-001243 01 
Page 3 of 13 
IRB Doc. Ctrl # 10013.27 
 
 
 
 
 
 
 
 
Name and Clinic Number 
 
 
Why are you being asked to take part in this research study? 
 
 
You are being asked to take part in this study because you have been identified as someone who 
has locally advanced or small volume metastatic pancreatic cancers or other solid tumors that is 
unable to undergo surgical resection. The overall study plans to enroll 30 subjects. Mayo Clinic 
plans to enroll 15 subjects. 
 
 
Why is this research study being done? 
 
 
The goal of this project is to transform the management of pancreatic cancer in the locally 
advanced and metastatic phases. This will be done by using photodynamic therapy, a new type 
of laser device, in combination with systemic therapy.  
We are doing research on this new method of treatment to find out if it is a less invasive option 
and is as effective as current treatment methods. 
 
 
Information you should know 
 
 
Who is Funding the Study? 
This study is being funded by the National Institute of Health (NIH). The Principal Investigator 
or the institution will otherwise cover the costs related to running the study. 
 
 
How long will you be in this research study? 
 
 
You will be in the study for one year, or until you decide to discontinue treatment. 
 
 
What will happen to you while you are in this research study? 
 
 
If you agree to be in the study, you will be asked to participate in the following: 


 
 
Approval Date:  
May 5, 2023 
Not to be used after: October 18, 2023 
 
IRB#: 16-001243 01 
Page 4 of 13 
IRB Doc. Ctrl # 10013.27 
 
 
 
 
 
 
 
 
Name and Clinic Number 
 
Patient Visit Schedule 
Screening 
Procedure Visit 
Day 
2 
Day 
3 
Day 
14 
Month 
3 
Month 
6 
Month 
12 
Physical Exam 
X 
  
X 
X 
X 
X 
X 
X 
CT Scan 
X 
  
  
X 
  
X 
X 
X 
Bloodwork 
X 
  
X 
X 
X 
X 
X 
X 
Questionnaires 
X 
  
  
  
X 
  
  
  
Endoscopy 
  
X 
  
  
  
  
  
  
Verteporfin 
Infusion and 
Photodynamic 
Therapy (PDT) 
 
 
X 
 
 
 
 
 
 
 
Screening Visit 
• During the screening visit, you will undergo a physical examination, you will have 
bloodwork and a CT scan done, and you will be asked to fill out quality of life 
questionnaires. 
 
Procedure Visit 
• An hour prior to the procedure, you will receive the study drug through an IV infusion. 
You will also be given an antibiotic to reduce the risk of inflammation before the 
procedure.  The physician will direct the endoscope that has an ultrasound to your 
pancreas, and the treatment laser will be guided to the sites on your pancreas where the 
tumors are located. This will be done using an ultrasound to find the tumor and place a 
needle from inside the stomach or small intestine into the tumor. This is a standard 
procedure for obtaining tissue from a tumor. In this study, a special fiberoptic probe will 
be placed through the needle to allow light to be delivered to the tumor. This probe can 
be seen by the ultrasound device to guide the probe the proper location. 
 


 
 
Approval Date:  
May 5, 2023 
Not to be used after: October 18, 2023 
 
IRB#: 16-001243 01 
Page 5 of 13 
IRB Doc. Ctrl # 10013.27 
 
 
 
 
 
 
 
 
Name and Clinic Number 
Immediate post-procedure 
• Immediately following the procedure, you will be placed in a low-light area in the 
Clinical Research and Trials Unit (CRTU) to minimize side effects from the study drug. 
After 24 hours, you will be gradually exposed to more light. After 48 hours, you will be 
exposed to direct sunlight, and your reaction to sunlight will be assessed. If severe side 
effects are present, further stay in a low-light area will be required. During the two day 
stay, a physical exam and bloodwork will be done. On the second day after the procedure 
(Day 3), a CT scan will be done to assess the state of your tumors. 
 
Post-procedure 
• Two weeks after the procedure, you will return for another visit to have another physical 
performed, bloodwork done, and you will fill out the quality of life questionnaires. 
• Following the two week visit, you will return 3 months, 6 months and one year after the 
date of the procedure to undergo a physical exam, bloodwork and a CT scan to assess the 
state of your tumors.  If you are unable to return for visits you will be contacted by phone 
at these time-points and asked the Quality of Life questionnaire, if you have been 
hospitalized related to disease, progression of disease or any adverse events, this will take 
approximately 5 minutes. 
 
 
What are the possible risks or discomforts from being in this 
research study? 
 
 
Verteporfin Infusion and Photodynamic Therapy (PDT) 
The major side effect of photodynamic therapy (PDT) with a verteporfin infusion is sensitivity to 
light. All patients who receive it will be sensitive to light for two to three days after the 
procedure. Because of this, you will spend the first day after the procedure in a room with very 
little light. Bright indoor light will be permitted after the initial one day period, but patients must 
observe precautions to avoid exposure of the eyes and skin to direct sunlight for at least two 
days. Patients who receive verteporfin can be safely exposed to sunlight only two days after 
sensitization. Some parts of your body may be more light sensitive than others.  
 
Before going outside, you should test a small area of skin in the light for 10 minutes to make sure 
the effects of the drug have worn off. If you don’t swell, get a rash or blisters within 24 hours, 
you can gradually resume normal outdoor activities, initially continuing to exercise caution and 
gradually allowing increased exposure. If a reaction occurs with the limited skin test, you should 
continue the existing precautions for another week before re-testing. Since the face is very 
sensitive, it is not recommended as a safe testing area. If you travel to a different geographical 
area with greater sunshine, you should retest your skin.  


 
 
Approval Date:  
May 5, 2023 
Not to be used after: October 18, 2023 
 
IRB#: 16-001243 01 
Page 6 of 13 
IRB Doc. Ctrl # 10013.27 
 
 
 
 
 
 
 
 
Name and Clinic Number 
Sunscreen will not help prevent side effects, because visible light, not UV, causes them. For 
three days following treatment, you should wear dark sunglasses when outdoors, and should 
consult your ophthalmologist if they notice any change in vision after treatment. You will be 
given information on barrier protection (hat, gloves, long sleeves etc) and an emergency contact 
number will be given. 
 
In addition to photosensitivity, you may experience a change in blood pressure due to the 
infusion. Abnormalities in blood tests related to the liver have been noted in up to 10% of 
patients receiving the study agent. Other potential side effects although rare include: pain, 
redness, swelling, or discoloration at the site of the injection, back pain during the infusion, dry 
eye, itchy eye, dry, itchy skin, constipation, nausea, muscle pain or weakness, decreased 
sensitivity to touch, or decreased hearing.  
 
You will be monitored closely during and after the drug administration by the providing 
physician and study staff to ensure your safety.  Many side effects go away shortly after 
phototherapy or verteporfin is stopped, but in some cases side effects can be serious, long lasting, 
or may never go away. There may be a risk of death.  Some side effects may not be known.  Side 
effects may range from mild to life-threatening. Other drugs may be given to make side effects 
less serious and less uncomfortable.  Talk to the researcher and/or your healthcare provider about 
side effects and ask any other questions. You may also feel some slight discomfort at the site of 
the infusion; however this is normal and is resolved quickly. 
 
Endoscopy 
The risks of participating in this study are those that typically occur any endoscopic procedure 
using local anesthesia with sedation (allergic reaction to medications used, bruising or pain at the 
intravenous access site, hypoventilation) and the passing of an endoscope through the esophagus 
(difficulty or pain with swallowing, strictures in the throat, sore throat).  The endoscopy itself 
may cause a cramping sensation in the stomach and you may feel bloated during the procedure 
because of air introduced into the stomach. The procedure is considered very safe, but it is 
possible to cause either bleeding or even a tear in the esophagus or stomach in rare (less than 1 in 
1000) cases. Inflammation of the pancreas (pancreatitis) is possible rare complication which may 
require hospitalization for observation. 
 
Antibiotics 
The risks of taking oral antibiotics include stomach discomfort, nausea, photosensitivity and 
possible allergic reactions. You will be monitored for any of these reactions while you take the 
antibiotic. 
 
 
 


 
 
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CT Scans 
CT uses X-rays to image the inside of your body. You will be exposed to additional radiation 
during the CT scans of your pancreas obtained for research. The amount of radiation you will 
receive has a low risk of harmful effects. Some people are given contrast material through a 
small tube inserted in their hand or arm, called receiving it intravenously or, “through an IV.” 
Contrast material is an iodine-based substance that helps highlight the area that needs to be seen 
more clearly on the scan. Problems from receiving IV contrast material are rare. If you know you 
are allergic to contrast material, talk to the health care provider who ordered your CT scan. You 
may have an increased risk of having problems from IV contrast material if you have heart 
disease, asthma, diabetes, kidney problems or thyroid disease. You may be asked to drink two or 
more glasses of oral contrast material to highlight your digestive tract, or you may be given the 
contrast material as an enema. Rarely, people have an allergic reaction, stomach cramps or 
diarrhea from drinking the contrast material or receiving the enema. If you have had a CT scan 
before and had these symptoms, tell a radiology nurse before your scan. 
 
Blood Draw 
The risks of drawing blood include pain, bruising, lightheadedness, and/or fainting, or rarely, 
infection at the site of the needle stick.  
 
Pregnancy 
The effects of the study drug on an unborn child are unknown. Because of this, if you are of 
childbearing potential, you will be required to undergo a pregnancy test before you enter the 
study. In addition to the pregnancy test, you will be required to use an adequate contraceptive 
method prior to entering the study and continue to use it for one week after the therapy. 
 
Financial risk  
Taking part in this research study may lead to added costs to you. In some cases, insurance will 
not pay for services ordinarily covered because these services were performed in a research 
study. You should check with your insurance company to see what services will be covered and 
what you will be responsible to pay. 
 
 
Are there reasons you might leave this research study early? 
 
 
You may decide to stop at any time.  If you cannot tolerate the treatment, you can inform the 
study staff that you will not like to participate and your participation will be terminated.   
 
In addition, the Principal Investigator or Mayo Clinic may stop you from taking part in this study 
at any time: 


 
 
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• if it is in your best interest,  
• if you don’t follow the study procedures,  
• if the study is stopped 
 
If you leave this research study early, or are withdrawn from the study, no more information 
about you will be collected; however, information already collected about you in the study may 
continue to be used. 
 
We will tell you about any new information that may affect your willingness to stay in the 
research study. 
 
 
What if you are injured from your participation in this research study? 
 
 
Where to get help: 
If you think you have suffered a research-related injury, you should promptly notify the Principal 
Investigator listed in the Contact Information at the beginning of this form. Mayo Clinic will 
offer care for research-related injuries, including first aid, emergency treatment and follow-up 
care as needed. 
 
Who will pay for the treatment of research related injuries: 
Care for such research-related injuries will be billed in the ordinary manner, to you or your 
insurance. Treatment costs for research-related injuries not covered by your insurance will be 
paid by Mayo Clinic 
 
 
What are the possible benefits from being in this research study? 
 
 
You may not directly benefit from taking part in this study. However, we hope that this study 
leads to quality of life improvements for you and future patients sharing your diagnosis. 
 
 


 
 
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What alternative do you have if you choose not to participate in this 
research study? 
 
 
If you choose not to participate in this study, your other option would be continuing your 
standard care. 
 
 
What tests or procedures will you need to pay for if you take part 
in this research study? 
 
 
You won’t need to pay for tests and procedures which are done just for this research study.  
These tests and procedures are: 
• Physical exams done for research  
• The verteporfin infusion and PDT 
• Physical exam 
• Questionnaires 
• All study related blood draws and pregnancy testing (if applicable) 
• All study related CT scans 
• The inpatient stay in the Clinical Trials Research Unit 
• The endoscopy for the PDT 
 
However, if there are other tests or procedures ordered by your physician, not related to this 
study or for incidental findings at the time of endoscopy you and/or your insurance will need to 
pay for all other tests and procedures that you would have as part of your clinical care. You will 
also be responsible for co-payments and deductibles. 
 
If you have billing or insurance questions call Patient Account Services at the telephone 
number provided in the Contact Information section of this form. 
 
 
Will you be paid for taking part in this research study? 
 
 
You will not be paid for taking part in this study. 
 
 


 
 
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What will happen to your samples? 
 
 
The only samples that will be collected for this study are blood samples. Your samples will be 
destroyed after analysis. The data collected from your samples will be shared with Massachusetts 
General Hospital and the National Institute of Health. 
 
 
How will your privacy and the confidentiality of your records be protected? 
 
 
Mayo Clinic is committed to protecting the confidentiality of information obtained about you in 
connection with this research study. Your information will be stored either in a locked cabinet on 
the Mayo Clinic Campus, or on a password protected server. 
 
During this research, information about your health will be collected.  Under Federal law called 
the Privacy Rule, health information is private.  However, there are exceptions to this rule, and 
you should know who may be able to see, use and share your health information for research and 
why they may need to do so.  Information about you and your health cannot be used in this 
research study without your written permission.  If you sign this form, it will provide that 
permission.   
 
Health information may be collected about you from: 
• Past, present and future medical records. 
• Research procedures, including research office visits, tests, interviews and 
questionnaires. 
 
Why will this information be used and/or given to others? 
• To do the research. 
• To report the results. 
• To see if the research was done correctly. 
 
If the results of this study are made public, information that identifies you will not be used. 
 
Who may use or share your health information? 
• Mayo Clinic research staff involved in this study.  
• Massachusetts General Hospital 
• National Institute of Health researchers 
 


 
 
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With whom may your health information be shared?  
• The Mayo Clinic Institutional Review Board that oversees the research.  
• Other Mayo Clinic physicians involved in your clinical care. 
• Researchers involved in this study at other institutions. 
• Federal and State agencies (such as the Food and Drug Administration, the Department of 
Health and Human Services, the National Institutes of Health and other United States 
agencies) or government agencies in other countries that oversee or review research. 
• The sponsor(s) of this study and the people or groups it hires to help perform this 
research. 
• A group that oversees the data (study information) and safety of this research. 
 
Is your health information protected after it has been shared with others? 
Mayo Clinic asks anyone who receives your health information from us to protect your privacy; 
however, once your information is shared outside Mayo Clinic, we cannot promise that it will 
remain private and it may no longer be protected by the Privacy Rule. 
 
 


 
 
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Your Privacy Rights 
You do not have to sign this form, but if you do not, you cannot take part in this research study. 
 
If you cancel your permission to use or share your health information, your participation in this 
study will end and no more information about you will be collected; however, information 
already collected about you in the study may continue to be used. 
 
If you choose not to take part or if you withdraw from this study, it will not harm your 
relationship with your own doctors or with Mayo Clinic. 
 
You can cancel your permission to use or share your health information at any time by sending a 
letter to the address below: 
 
Mayo Clinic 
Office for Human Research Protection 
ATTN:  Notice of Revocation of Authorization 
200 1st Street SW 
Rochester, MN  55905 
 
Alternatively, you may cancel your permission by emailing the Mayo Clinic Research 
Participant Advocate at: researchparticipantadvocate@mayo.edu 
Please be sure to include in your letter or email: 
• The name of the Principal Investigator, 
• The study IRB number and /or study name, and 
• Your contact information. 
 
Your permission lasts until the end of this study, unless you cancel it.  
 
 


 
 
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ENROLLMENT AND PERMISSION SIGNATURES 
 
 
Your signature documents your permission to take part in this research. 
 
 
 
  
 
 
 
/        /  
 
 
   : 
       AM/PM   
Printed Name  
 
 
 
Date 
 
 
 
Time   
 
 
 
 
_______________________________ 
Signature 
 
 
 
Person Obtaining Consent  
• I have explained the research study to the participant. 
• I have answered all questions about this research study to the best of my ability. 
 
 
 
  
 
 
 
/        /  
 
 
   : 
       AM/PM   
Printed Name  
 
 
 
Date 
 
 
 
Time           
 
 
_______________________________ 
Signature