Mucinous Pancreatic Cysts
Conditions
Keywords
pancreatic cyst, chemotherapy, ethanol, ablation
Brief summary
The purpose of this study is to evaluate the efficacy of a chemotherapeutic cocktail with or without prior ethanol lavage for ablation of premalignant pancreatic cysts using endoscopic ultrasound-guided fine needle injection (EUS-FNI) for agent delivery.
Detailed description
While about half of pancreatic cystic lesions have little to no malignant potential, mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs) carry a high potential for progression into pancreatic cancer. Therefore, either close radiographic surveillance or surgical resection is generally recommended for these cysts. However, pancreatic surgery is associated with a significant risk of morbidity and mortality and not all patients are good surgical candidates. As an alternative, endoscopic ultrasound-guided fine needle injection(EUS-FNI) has been shown to be moderately effective in ablating cystic lesions. The goal of this investigation is to improve the efficacy and safety of this procedure when compared with previous versions of the technique. This study is designed to evaluate the efficacy of a chemotherapeutic cocktail with or without prior ethanol lavage for ablation of pancreatic cystic neoplasms using EUS-FNI for agent delivery. This paired, prospective, double-blind, randomized study will include 78 patients referred to the Penn State Hershey Medical Center. Mucinous or indeterminate pancreatic cysts of 1-5cm with less than 5 compartments and without clear communication with the main pancreatic duct will be included. Patients will be randomized in a 1:1 ratio into a control arm or study arm. Patients randomized to the control arm will receive ethanol lavage of the cyst followed by injection of two carefully selected chemotherapeutic agents. Study arm patients will receive a normal saline lavage followed by injection of the same chemotherapy admixture. Patients will be monitored for 2 hours post-procedure, and a follow-up CT will be performed at 6, and 12 months, or as determined necessary to evaluate cyst resolution. Patients may elect to undergo evaluation for surgical resection at any time, regardless of response, in which case a dedicated pathologist will evaluate any surgical specimens.
Interventions
DRUGEthanol
Cysts will be lavaged for 3-5 minutes with 80% EtOH
DRUGNormal Saline
Cysts will be lavaged for 3-5 minutes with normal saline
DRUGChemotherapy
Following lavage with either 80% ethanol (control group) or normal saline (study group), cysts will be injected with a cocktail of 3mg/ml paclitaxel and 19mg/ml gemcitabine.
Sponsors
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients age 18 and older of any gender, ethnicity and race * Voluntary enrollment and ability to give written informed consent * Capable of safely undergoing endoscopy with deep sedation or general anesthesia * Patients with previously-detected pancreatic cyst(s) 1-5 cm in diameter, including indeterminate cysts
Exclusion criteria
* Pancreatic cyst \<1cm or \>5cm * Pancreatic cyst with clear communication with main pancreatic duct * Clearly benign lesions by clinical and radiographic evaluation (pseudocysts and serous cystadenomas) * Known or suspected pancreatic cancer or pathologic lymphadenopathy * Septated cysts with \> 5 compartments * Coagulopathy (international normalized ratio \> 1.6, platelets \< 30,000) * Evidence of active pancreatitis or pancreatic infection * Patients having undergone endoscopic retrograde cholangiopancreatography (ERCP) within 72 hours * Baseline lab values at the time of consent: white blood cells \> 14 or \< 2, hematocrit \< 30, platelets \< 30,000, INR \> 1.6, abnormal CA19-9, lipase \> 3 times the upper limit of normal, creatinine \> 2.5, ALT \> 210, total bilirubin \> 2.5, positive qualitative beta-hCG. * Any pre-existing or discovered medical condition that may, at the discretion of the investigator, interfere with the completion of and/or participation in the existing protocol. * Pregnant, breastfeeding, or incarcerated individuals
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With the Changing in Cyst Volume | 6, and 12 months post procedure | The primary outcome of interest will be change in cyst size, as measured on initial, 6, and 12 month CT/MRI, or as determined necessary to evaluate cyst resolution. Cyst size was calculated by measuring x and y diameters and calculating cyst volume using the formula:4/3xpxr3 where r is the average of the cyst radius as measured on the initial, 6-month, and 12-month magnetic resonance imaging or computed tomography. Response was defined according to the same volume percentage reductions as described in previous trials where: complete response is a =\>95% reduction in cyst volume, partial response is a 94%-75% reduction, and anon-response is \<75% reduction in volume.11 The overall ablation rates in both arms were also compared with historical controls to assess the efficacy of the chemotherapeutic cocktail. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Group Ethanol: Cysts will be lavaged for 3-5 minutes with 80% EtOH
Chemotherapy: Following lavage with either 80% ethanol (control group) or normal saline (study group), cysts will be injected with a cocktail of 3mg/ml paclitaxel and 19mg/ml gemcitabine. | 18 |
| Study Group Normal Saline: Cysts will be lavaged for 3-5 minutes with normal saline
Chemotherapy: Following lavage with either 80% ethanol (control group) or normal saline (study group), cysts will be injected with a cocktail of 3mg/ml paclitaxel and 19mg/ml gemcitabine. | 21 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | cyst found to be prohibitively small | 0 | 1 |
| Overall Study | excessive main duct communication | 1 | 1 |
| Overall Study | Loss of needle positioning due pt. cough | 1 | 0 |
| Overall Study | Osteophyte obstruction of the proximal | 1 | 0 |
| Overall Study | Sign of malignancy during the procedure | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Control Group | Study Group |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 27 Participants | 14 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 16 Participants | 19 Participants |
| Region of Enrollment United States | 39 Participants | 18 Participants | 21 Participants |
| Sex: Female, Male Female | 23 Participants | 13 Participants | 10 Participants |
| Sex: Female, Male Male | 16 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 21 |
| other Total, other adverse events | 4 / 18 | 0 / 21 |
| serious Total, serious adverse events | 1 / 18 | 0 / 21 |
Outcome results
Primary
Number of Participants With the Changing in Cyst Volume
The primary outcome of interest will be change in cyst size, as measured on initial, 6, and 12 month CT/MRI, or as determined necessary to evaluate cyst resolution. Cyst size was calculated by measuring x and y diameters and calculating cyst volume using the formula:4/3xpxr3 where r is the average of the cyst radius as measured on the initial, 6-month, and 12-month magnetic resonance imaging or computed tomography. Response was defined according to the same volume percentage reductions as described in previous trials where: complete response is a =\>95% reduction in cyst volume, partial response is a 94%-75% reduction, and anon-response is \<75% reduction in volume.11 The overall ablation rates in both arms were also compared with historical controls to assess the efficacy of the chemotherapeutic cocktail.
Time frame: 6, and 12 months post procedure
Population: Intent to treat population (all participants at least one dose of intervention)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control Group | Number of Participants With the Changing in Cyst Volume | No Response after 12 months | 3 Participants |
| Control Group | Number of Participants With the Changing in Cyst Volume | Partial Response after 6 months | 5 Participants |
| Control Group | Number of Participants With the Changing in Cyst Volume | Partial Response after 12 months | 4 Participants |
| Control Group | Number of Participants With the Changing in Cyst Volume | No Response after 6 months | 6 Participants |
| Control Group | Number of Participants With the Changing in Cyst Volume | Complete Response after 12 months | 11 Participants |
| Control Group | Number of Participants With the Changing in Cyst Volume | Complete Response after 6 mon | 6 Participants |
| Study Group | Number of Participants With the Changing in Cyst Volume | Complete Response after 12 months | 14 Participants |
| Study Group | Number of Participants With the Changing in Cyst Volume | No Response after 6 months | 5 Participants |
| Study Group | Number of Participants With the Changing in Cyst Volume | Partial Response after 12 months | 3 Participants |
| Study Group | Number of Participants With the Changing in Cyst Volume | No Response after 12 months | 4 Participants |
| Study Group | Number of Participants With the Changing in Cyst Volume | Complete Response after 6 mon | 12 Participants |
| Study Group | Number of Participants With the Changing in Cyst Volume | Partial Response after 6 months | 4 Participants |