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

Trial Status: Active

The purpose of this study is to evaluate the efficacy and safety of chemotherapeutic pancreatic cyst ablation using ethanol lavage followed by the infusion of a dual-agent chemotherapeutic cocktail (paclitaxel + gemcitabine) compared with alcohol-free saline lavage followed by infusion of the same dual-agent chemotherapeutic cocktail (paclitaxel + gemcitabine) for the ablation of pancreatic cystic neoplasms using endoscopic ultrasound guided fine needle infusion (EUS-FNI) for agent delivery.

Inclusion Criteria

  • Adult subjects over the age of 18.
  • Patients with a previously-detected pancreatic cyst(s) 2-5 cm in diameter which is consistent with a mucinous type cyst as per ASGE guidelines, including indeterminate type cysts.
  • Able to give written informed consent.
  • Capable of safely undergoing endoscopy with deep sedation or general anesthesia.

Exclusion Criteria

  • Lesions which are consistent with a benign cyst by clinical, cytological, chemical, and radiographic evaluation as per ASGE guidelines (i.e., consistent with a pseudocyst or serous cystadenoma).
  • Known or suspected pancreatic cancer or pathologic lymphadenopathy.
  • Cysts with the following high-risk features: main pancreatic duct dilation of > 5mm, epithelial type mural nodules (> 2mm)33, pathologically thick wall/septation (> 2mm), cytology showing high grade dysplasia or "suspicious for malignancy", signs of common bile duct or pancreatic duct obstruction, solid mass component within or associated with the cyst (> 2mm), pancreatic duct stricture associated with tail atrophy, or previous fine needle aspiration failure due to excessive cyst fluid viscosity. (Of note, the following higher-risk features ARE eligible: recent growth in size, atypical cells on cytology, and symptoms referable to the pancreas.)
  • Septated cysts with > 4 compartments.
  • Confirmed pancreatitis within the last 3 months.
  • Baseline lab values (must be within 6 months of consent date) in the following ranges: white blood cells > 14 or < 2 K/uL, hematocrit <30%, platelets <30 K/uL, non-pharmacologic INR >1.7, CA19-9 >2x ULN, lipase >2x ULN, creatinine >3.0 mg/dl (unless stable on renal replacement therapy), ALT >500 U/L, total bilirubin >2.5 mg/dl.
  • Any pre-existing or discovered medical condition that would, at the discretion of the investigator, interfere with the completion of and/or participation in the existing protocol. This includes severe pre-existing medical conditions which would preclude a reasonable 5 year life expectancy (and thus neutralize the patient's benefit from ablating a premalignant type pancreatic cyst).
  • Pregnancy, breastfeeding, or incarcerated individual.

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: ACTIVE

Pennsylvania

Hershey
Penn State Milton S Hershey Medical Center
Status: ACTIVE
Contact: Matthew T. Moyer
Phone: 717-531-3694

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 98%

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.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Penn State Milton S Hershey Medical Center

  • Primary ID 5206
  • Secondary IDs NCI-2019-07724, 1R01CA222648
  • Clinicaltrials.gov ID NCT03085004