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

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ClinicalTrials.gov Identifier: NCT03085004
Recruitment Status : Recruiting
First Posted : March 21, 2017
Last Update Posted : March 26, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Matthew T. Moyer, Milton S. Hershey Medical Center

Tracking Information
First Submitted Date  ICMJE March 9, 2017
First Posted Date  ICMJE March 21, 2017
Last Update Posted Date March 26, 2021
Actual Study Start Date  ICMJE April 12, 2019
Estimated Primary Completion Date April 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 15, 2018)
  • Percentage of subjects achieving complete cyst resolution at 12 months [ Time Frame: 12 months post initial treatment ]
    This is defined as Complete response greater than or equal to 95% reduction in cyst volume and measured by "r" as cyst volume 4/3×π×r3 at 12 months post initial treatment
  • Incidence of serious and minor adverse events occurring within 30 days post ablation [ Time Frame: 30 days post EUS-FNI procedure ]
    Based on definition of serious and minor adverse events, the two arms will be compared with respect to adverse events that took place within 30 days after the subject's procedure
Original Primary Outcome Measures  ICMJE
 (submitted: March 14, 2017)
percentage of cyst achieving complete ablation . This is defined as Complete response = >= 95% reduction in cyst volume and measured by "r" as cyst volume 4/3×π×r3 at 12 mon post initial treatment [ Time Frame: 12 months post initial treatment ]
The primary outcome of interest will be the percentage of cysts achieving complete ablation at 12 months
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2017)
  • Measure of within 30 days of the procedure adverse events [ Time Frame: 30 days post procedure ]
    The secondary outcome of interest will be measure of moderate and major
  • Change in cyst volume [ Time Frame: 3 and 12 months post initial treatment ]
    The Secondary outcome of interest will be change in cyst size, as measured on 3 and 12 months post initial treatment
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CHARM II: Chemotherapy for Ablation and Resolution of Mucinous Pancreatic Cysts
Official Title  ICMJE CHARM II: Chemotherapy for Ablation and Resolution of Mucinous Pancreatic Cysts: a Prospective, Randomized, Double-blind, Multi-center Clinical Trial
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Pancreatic Cyst
  • EUS-FNA
Intervention  ICMJE
  • Drug: Ethanol
    The cyst will be lavaged for 3 to 5 minutes using 98% ethanol as the lavage agent prior to infusing the cyst with the paclitaxel + gemcitabine admixture.
  • Drug: Normal saline
    The cyst will be lavaged for 3 to 5 minutes using normal saline as the lavage agent prior to infusing the cyst with the paclitaxel + gemcitabine admixture.
  • Drug: Paclitaxel + Gemcitabine admixture
    Following lavage, cysts will be infused with an admixture of 3mg/ml paclitaxel and 19mg/ml gemcitabine.
Study Arms  ICMJE
  • Active Comparator: Control Group
    Cyst will be lavaged for 3 to 5 minutes with 98% ethanol. Following lavage with 98% ethanol, the cyst will be infused with an admixture of (3mg/ml paclitaxel + 19mg/ml gemcitabine).
    Interventions:
    • Drug: Ethanol
    • Drug: Paclitaxel + Gemcitabine admixture
  • Experimental: Study group
    Cyst will be lavaged for 3 to 5 minutes with normal saline. Following lavage with normal saline, the cyst will be infused with an admixture of (3mg/ml paclitaxel + 19mg/ml gemcitabine).
    Interventions:
    • Drug: Normal saline
    • Drug: Paclitaxel + Gemcitabine admixture
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 14, 2017)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date April 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Matthew T. Moyer, MD, MS 717-531-3694 mmoyer@pennstatehealth.psu.edu
Contact: Courtney Lester 717-531-0003 ext 287992 clester1@pennstatehealth.psu.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03085004
Other Study ID Numbers  ICMJE 5206
1R01CA222648 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Matthew T. Moyer, Milton S. Hershey Medical Center
Study Sponsor  ICMJE Milton S. Hershey Medical Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Matthew T. Moyer, MD, MS Penn State Health Milton S. Hershey Medical Center
PRS Account Milton S. Hershey Medical Center
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP