CHARM II: Chemotherapy for Ablation and Resolution of Mucinous Pancreatic Cysts

Pancreatic cystic lesions are increasingly encountered and typically discovered

incidentally on cross-sectional imaging, occurring in approximately 2% of all American

adults with a 37% prevalence in individuals over 80. Most of these cysts are mucinous

(neoplastic) in origin and represent precursor lesions for pancreatic adenocarcinoma.

Discovering a pancreatic cyst typically presents a treatment dilemma, with options

including either indefinite radiographic surveillance with MR (magnetic resonance) or CT

imaging or surgical resection, both of which have significant limitations. Surveillance

carries significant economic and possible psychological burdens while waiting for signs

of malignancy to develop, as well as radiation exposure with computed tomography. On the

other hand, surgical resection possesses a significant risk of serious adverse events

(20%-40%) and mortality (1-2%). This clinical dilemma delineates the pressing need to

develop effective, but more minimally invasive approaches for the elimination of these

premalignant pancreatic cysts, and among these, endoscopic ultrasound guided fine needle

infusion (EUS-FNI) has emerged as an innovative and promising approach. Between November

2011 and December 30, 2015, investigators from interventional endoscopy, surgical

oncology, hematology oncology, and pathology of the Penn State Hershey Medical Center

conducted the CHARM I clinical trial. This was a prospective, randomized, double-blind,

single-center study with an N of 46 patients required for 80% power to prove

non-inferiority. Final results from CHARM I were as follows: Patients treated included 23

females and 16 males with the majority of lesions located in the body and head of the

pancreas. Both the alcohol and alcohol-free groups recorded a 47% rate of complete

ablation at 6 months, which increased to 64% for both groups at the 1 year follow-up. One

subject experienced a complication in the alcohol arm (6%), and no subjects experienced

complications in the alcohol-free arm.

The overall objectives of CHARM II are to verify the significant findings of CHARM I in a

multi-center clinical trial as requested by national investigators in this field. We

expect that administering a specifically designed chemotherapeutic cocktail without prior

ethanol lavage will result in an equivalent rate of cyst resolution with fewer

complications when compared with lavage using alcohol. The results of this study will

provide important information about the most efficient and safest method for treating

premalignant pancreatic cysts, an important step for treating these lesions with a

minimally invasive technique and preventing their progression to pancreatic cancer.

Standard alternative treatment options for this patient group (if not taking part in this

study) would be ongoing periodic radiographic surveillance with MR or CT imaging waiting

for signs of malignancy to develop or to consider surgical resection (an option with

significant rates of morbidity and mortality).

This is an investigator-initiated, prospective, randomized, double-blinded, multi-center

study evaluating ethanol lavage and chemotherapy for the ablation of mucinous and

indeterminate type pancreatic cysts with malignant potential. Participants will be

screened for the study according to inclusion and exclusion criteria. After confirming

their eligibility, patients will be randomized to one of the following EUS-FNI treatment

arms in a 1:1 ratio:

Control arm: After removal of cyst fluid, cysts will be lavaged for 3 to 5 minutes with

>/=99% ethanol and then infused with an admixture of 3 mg/ml paclitaxel and 19 mg/ml

gemcitabine.

Experimental arm: After removal of cyst fluid, cysts will be lavaged for 3 to 5 minutes

with normal saline and then infused with an admixture of 3 mg/ml paclitaxel and 19 mg/ml

gemcitabine.

Patients will be contacted by the study team via phone call at both 72 hours and 30 days

after their EUS procedure to assess any adverse events that may have occurred. Within 2-3

weeks of the having the EUS procedure, patients will receive the cyst fluid pathology

results. At 3 months after the initial procedure, patients will undergo a follow-up EUS

examination in the same manner as the initial EUS exam. During this exam, a complete

pancreaticobiliary evaluation will be conducted, and the diameter of the previously

treated cyst will be measured in the x and y dimensions to assess the 3 month response.

Any cyst still >15mm and amenable to repeat ablation will undergo a second EUS-guided

chemoablation treatment using the same lavage that the patient was randomized to

initially. At both 12 months and 24 months after the initial procedure, the patient will

be seen in the GI clinic and undergo either an MRI-MRCP (magnetic resonance

cholangiopancreatography) or enhanced CT scan for a full pancreaticobiliary evaluation to

assess the end-point treatment response.