Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Cysts

Pancreatic Cyst

Pathological Conditions, Anatomical

Pancreatic Diseases

Gastrointestinal Diseases

This study evaluates the use of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) and cyst fluid molecular analysis in the differential diagnosis of pancreatic cysts and the detection of malignancy.

Pancreatic cyst are a frequent finding on cross-sectional imaging on general population. They are identified in up to 3% of the abdominal computed tomographies (CT) and 20% of magnetic resonance imaging (MRI) performed for other reasons but the risk of malignancy in pancreatic cysts discovered incidentally is low, representing 1-5% of the total malignant pancreatic neoplasms.

Pancreatic cysts are a broad group of pancreatic lesions that can be divided into benign and premalignant or malignant lesions. Pseudocyst and serous cystic neoplasm (SCN) don´t have malignant potential while others like mucinous cysts are premalignant lesions. But not all mucinous neoplasms have the same risk of malignancy. According to recent publications mucinous cystic neoplasm (MCN) have a potential for malignancy of around 15%, main duct intrapapillary mucinous neoplasm (MD-IPMN) of 62% and branch duct IPMN (BD-IPMN) of 25%. The correct identification of these premalignant lesions will allow to optimize the treatment and follow-up of these patients, but in many cases it is difficult to accurately differentiate between different types of cysts and their risk of malignancy. The differentiation between lmucinous and non-mucinous cysts is suboptimal, with diagnostic accuracy for CT and MRI of 61% and 50-73% with endoscopic ultrasound (EUS). The endosonographic characteristics that have been related with malignancy are the size larger than 3 cm, the presence of a solid component, wall thickening, Wirsung dilation, abrupt change of the size of the main pancreatic duct with distal atrophy of the gland and the presence of lymphadenopathies. However, endosonographic characteristics are not sufficient as an individual predictor of malignancy.

The puncture of the cyst and fine-needle aspiration (EUS-FNA) with biochemical and cytological assessment is generally indicated to differentiate between cysts and to asses for malignancy. The determination of carcinoembryonic antigen (CEA) and amylase have low specificity for the detection of malignancy and for mucinous cyst, and the cytological assessment is highly specific but lacks of sensibility (50%). So further methods are requested for an adequate detection of premalignant and malignant cyst.

Contrast-enhanced harmonic endoscopic ultrasound uses an ultrasonographic contrast agent to visualize blood flow in fine vessels and may aid in the diagnosis of pancreatic cysts by enabling assessment of the vascularization of structures such as cyst walls, septa, or mural nodules. Furthermore it allows the correct differentiation between contrast-enhanced mural nodules, that predict for malignancy, from non-enhancing mucus clots.

The molecular analysis of cyst fluid may detect mutations that are associated with premalignant cyst and with malignancy. Kirsten rat sarcoma (KRAS) gene has been related with mucinous cyst while von Hippel-Lindau gene (VHL) is present in serous cyst.

This study evaluates the use of contrast-enhanced EUS and the molecular analysis for pancreatic cyst diagnosis and malignant detection, and if their use may modify cyst management.

Contrast Enhanced Ultrasound and Molecular Analysis in the Diagnosis of Pancreatic Cyst

Prospective Analysis About the Utility of Contrast Enhanced Endoscopic Ultrasound and Molecular Analysis in the Study of Pancreatic Cyst

Number and type of mutations that are present on the molecular analysis of premalignant and malignant mucinous cyst.

To evaluate the correlation between morphological diagnosis made by endoscopic ultrasound and diagnosis made by cyst fluid analysis (biochemical, cytological and molecular)

Percentage of pancreatic cyst that can be correctly diagnosed with contrast-enhanced EUS compared to EUS alone

Number of adverse events that happen during or 7 days after de procedure

Percentage of mutations that are present in both pancreatic cyst fluid and serum or only in cyst fluid

Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Neoplasms, Cystic, Mucinous, and Serous

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Central Nervous System Depressants

All Drugs and Chemicals

Anti-Arrhythmia Agents

Channel Blockers

Pharmaceutical Solutions

Anti-Infective Agents

Anesthetics

Lidocaine

Anesthetics, Local

Ethanol

Sodium Channel Blockers

Diuretics, Potassium Sparing

Anti-Infective Agents, Local

EUS-guided lavage of a pancreatic cyst with ethanol solution. The ethanol solution was diluted to 80% using normal saline. Final solution also contained 1% lidocaine except in patients allergic to local anesthetics. The ethanol solution was injected into pancreatic cysts at a volume equal to 90% of the aspirated cyst volume. In subjects undergoing re-treatment of a cyst, ethanol was diluted to 90% using normal saline, and injected in a volume equal to 100% of the aspirated cyst volume.

EUS-guided lavage of a pancreatic cystic neoplasm with ethanol solution. Ethanol was diluted to 80% using normal saline.

The final solution contained 1% lidocaine except in subjects allergic to local anesthetics.

Mark Topazian, MD

Cystic tumors of the pancreas are fluid-filled growths. They are often treated by surgical removal. A safe and effective non-surgical treatment is desirable. Ethanol (alcohol) injection may treat cysts by killing the lining cells of the cyst, and is an accepted treatment for cysts of other organs. In this study, participants with pancreatic cysts underwent endoscopic ultrasound (EUS) guided ethanol injection of pancreatic cysts. This was a pilot study to assess safety and efficacy.

The hypotheses of this study were 1) complications of EUS guided ethanol injection requiring hospitalization will occur in \<10% of subjects, and 2) EUS guided ethanol injection, with retreatment as necessary, will ablate at least 50% of pancreatic cysts.

EUS is performed via the mouth under sedation. After a needle is placed into the pancreas cyst under EUS guidance, an ethanol solution is placed into the cyst via the needle. The ethanol solution is withdrawn and new ethanol injected, and this process is continued for 5 minutes, repeatedly washing the cyst with the ethanol solution.

After this treatment, usual clinical follow-up is obtained including assessments of the cyst by CT or MRI scans. If a cyst of significant size persists, additional EUS-guided ethanol injections of the cyst were offered.

Endoscopic Ultrasound-guided Ethanol Injection of Pancreatic Cystic Neoplasms

Data sharing can be arranged and will require IRB approval

Adverse events include pancreatitis, bleeding, perforation, any other occurrence resulting in hospitalization, medical treatment, surgery, death, or disability

Complete or partial ablation of cysts will be defined by the presence of a persistent cystic structure, and its volume and maximum diameter, as determined by cross-sectional imaging studies (CT, MR)

Mayo Clinic

Professor of Medicine

Pancreatic Cyst Ethanol Injection

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Only subjects who received the study intervention, endoscopic ultra sound (EUS)- guided ethanol lavage were included in the baseline analysis.

Sample size was small, and a control group was not included. Neither cyst histology not degree of epithelial ablation was assessed by surgical resection in any of the study participants.

Dr. Mark Topazian

Number of participants with adverse events

Number of participants without adverse events

Number of Participants With Adverse Events as a Measure of Safety and Tolerability

Complete ablation of treated cyst

Greater than or equal to 80% cyst volume reduction

Less than 80% cyst volume reduction

Cyst volume increase

Number of Subjects With Complete or Partial Ablation of the Treated Cyst

Endoscopic ultrasound (EUS)-guided lavage of a pancreatic cyst with ethanol solution. The ethanol solution was diluted to 80% using normal saline. Final solution also contained 1% lidocaine except in patients allergic to local anesthetics. The ethanol solution was injected into pancreatic cysts at a volume equal to 90% of the aspirated cyst volume. In subjects undergoing re-treatment of a cyst, ethanol was diluted to 90% using normal saline, and injected in a volume equal to 100% of the aspirated cyst volume.

Overall Study

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Endocrine System Diseases

Pancreatic Cancer

Micronutrients

Gastrointestinal Agents

Vitamins

Tocopherols

Vitamin E

Tocotrienols

alpha-Tocopherol

Pancrelipase

Pancreatin

Trace Elements

Antioxidants

Protective Agents

Tocopherol

Tocotrienol

Vitamin E δ-Tocotrienol will be administered orally as a single agent twice daily for 14 consecutive days and one dose on Day 15.

Vitamin E δ-Tocotrienol is supplied as 100-mg, 200-mg, and 400-mg capsules. The investigator (or designee) will have records of the number of participants treated within a specific cohort and will determine which treatment cohort to assign newly enrolled participants.

Vitamin E δ-Tocotrienol

Gregory Springett, M.D., Ph.D.

The purpose of this study is to determine the safest dose of the study drug Vitamin E Delta-tocotrienol, how often it should be taken, and how well people with pancreatic tumors tolerate Vitamin E Delta-tocotrienol.

Delta-tocotrienol is a natural Vitamin E compound that has been consumed by humans as a dietary supplement. The Food and Drug Administration (FDA) has not approved it for sale as a drug. Vitamin E Delta-tocotrienol is being investigated for the prevention and treatment of pancreatic tumors. The usefulness of the Vitamin E Delta-tocotrienol in treating human tumors is unknown.

This study consists of the following: (1) a Pre-Treatment Period in which participants are consented and qualified for the study; (2) a Study Treatment Period in which participant will receive Vitamin E δ-Tocotrienol administered orally twice daily for 14 (±2) consecutive days and once on the day of surgery, with associated pharmacokinetic and pharmacodynamic sampling; (3) a Post Treatment Period in which laboratory and physical examinations are performed. Adverse events will be recorded throughout the study.

Vitamin E δ-Tocotrienol Administered to Subjects With Resectable Pancreatic Exocrine Neoplasia

A Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Vitamin E δ-Tocotrienol Administered to Subjects With Resectable Pancreatic Exocrine Neoplasia

To determine the recommended Phase II dose of Vitamin E δ-Tocotrienol which will be defined as the biologic effective dose (BED) which induces significant apoptosis in the pancreatic neoplastic cells of resected tumor specimens following oral administration of Vitamin E δ-Tocotrienol twice daily for 14 (± 2)days prior to surgery, and one dose the day of surgery.

To characterize the safety and tolerability of Vitamin E δ-Tocotrienol when orally administered at up to 5.6 times the predicted biological effective dose (1600mg twice daily) for 14 (± 2) consecutive days and one dose the day of surgery in patients with pancreatic neoplasia.

National Cancer Institute (NCI)

H. Lee Moffitt Cancer Center and Research Institute

Mucocele

Cystadenoma

Cystadenoma, Serous

Pancreatic Intraductal Neoplasms

The registry will be populated with a retrospective cohort of patients previously identified as having pancreatic cysts.

The prospectively enrolled patients in this study are the primary population of interest.

There are no study-specific interventions, as this is a prospective registry. However, patients will be asked to complete approximately 1-2 hours worth of surveys on things such as demographics, medical and surgical history, and pancreatic cyst-specific questionnaires.

Survey

Charysa Santos, BS

Kimberly S Kirkwood, MD

M.D.

Kimberly Kirkwood, MD

Paige M Bracci, PhD, MPH, MS

Pancreatic cysts are found incidentally on 15-50% of CT and MRIs for all indications and their prevalence is increasing. Many of these cysts may be precursors to pancreatic cancer, and thus pose a substantial risk, however, the vast majority are benign. Increased detection of pancreatic cysts provides an opportunity to diagnose pancreatic malignancy at an early, curable stage yet also increases the potential to over-treat clinically insignificant lesions. This presents a clinical challenge to prevent unnecessary resection of indolent disease, with associated risks of infections, bleeding, diabetes, and costly disability. Unfortunately, there is little information on the epidemiology and natural history of pancreatic cysts to help guide management.

This study develops a large, prospectively managed, electronic, patient-directed pancreatic cyst registry based at UCSF. The UCSF Pancreatic Cystic Lesions Registry (PANC Cyst) will facilitate work to improve clinical care and understanding of pancreatic cysts by prospective follow-up of patients with cystic lesions, especially the diagnostically challenging small cysts, to identify factors related to cyst formation and progression to malignancy. Longitudinal data capture that includes clinical outcomes will also enable us to more precisely define anatomic, radiographic and biomarker information that can be used to differentiate populations of patients for whom surgery is indicated, surveillance is warranted, or no further evaluation is necessary.

Patients in this study will have the option of donating blood for biobanking, approximately 10cc of plasma and 10cc of serum. Patients will also have the opportunity to donate a saliva sample at the time of study registration, or at a later date.

Further, samples that are routinely collected for diagnostic purposes may be collected and banked at the time of their clinically routine procedure. If a patient consents to the use of extra material for research purposes, the biological samples will be banked and the blood, and/or pancreatic juice/cystic fluid, tissues, and saliva will be used for identification and characterization of potential biomarkers from de-identified samples.

UCSF PANC Cyst Registry

Population-Based Analysis of Neoplastic Changes in Cystic Lesions of the Pancreas.

While not the primary outcome measure, the development of cancer from a pancreatic cyst is a critically important study endpoint, which the investigators do not expect to be frequent occurrence.

If a patient with a pancreatic cyst experiences no or minimal change in size, and no development of worrisome or high-risk stigmata (Tanaka 2017), this will be considered to be an indolent lesion. Most patients will fall under this category.

University of California, San Francisco

Antineoplastic Agents

Paclitaxel

Albumin-Bound Paclitaxel

Single intracystic injection of NanoPac® at a dose of 6 mg/mL in a volume sufficient to fill the cyst, at least equal to the amount of cyst fluid aspirated

Single intracystic injection of NanoPac® at a dose of 10 mg/mL in a volume sufficient to fill the cyst, at least equal to the amount of cyst fluid aspirated

Single intracystic injection of NanoPac® at a dose of 15 mg/mL in a volume sufficient to fill the cyst, at least equal to the amount of cyst fluid aspirated

Intracystic injection of NanoPac®. The dose administered in the second phase will be determined during the dose escalation phase. Subjects will receive two NanoPac® injections, with the second injection administered 12 weeks after the first injection.

NanoPac® (Sterile Nanoparticulate Paclitaxel) for intracystic injection via endoscopic ultrasound-guided injection (EUS-FNI)

NanoPac®

This study will evaluate intracystic NanoPac® (Sterile Nanoparticulate Paclitaxel) administered via endoscopic ultrasound-guided fine needle injection (EUS-FNI) in subjects with mucinous cystic pancreatic neoplasms.

In this open-label, dose rising trial, subjects with mucinous cystic pancreatic neoplasms will receive intracystic NanoPac® via endoscopic ultrasound-guided fine needle injection (EUS-FNI).

In the dose escalation phase, subjects will be enrolled in sequential cohorts of NanoPac® at 6, 10, and 15 mg/mL at volumes sufficient to fill the cyst, at least equal to the amount of cyst fluid aspirated. Each cohort will have three subjects, with cohorts enrolled sequentially starting at the lowest concentration. Following Data Safety Monitoring Board (DSMB) review of the cohort data, the next cohort may begin enrolling, an additional three at the current dose may be enrolled, or if the first dose does not provide adequate safety and tolerability the study may be halted. The dose determined to be the most suitable for further evaluation, defined as the highest dose with an acceptable safety and tolerability profile (as determined by the DSMB), will be the dose used in the second phase of the study which will enroll 9 additional subjects. Subjects enrolled in the second phase of the study will also receive a second injection of NanoPac at the same dose 12 weeks after the first NanoPac injection..

Plasma samples will be taken on the day(s) of NanoPac® injection at 1 and 2 hours after injection, as well as at each of the subsequent study visits, to characterize the pharmacokinetics (PK) of intracystic NanoPac®.

Subjects will be followed for 6 months after the first NanoPac® injection for safety, tolerability and cyst response to therapy (as shown by imaging).

Open-label, dose rising trial. During the dose escalation phase, subjects will be enrolled in sequential cohorts of NanoPac®. Each cohort will have three subjects, with cohorts enrolled sequentially starting at the lowest concentration. Following DSMB review of the cohort data, the next cohort may begin enrolling, an additional three subjects at the current dose may be enrolled, or, if the first dose does not provide adequate safety and tolerability, the study may be halted. The dose determined to be the most suitable for further evaluation, defined as the highest dose with an acceptable safety and tolerability profile (as determined by the DSMB), will be the dose used in the second phase of the study which will enroll 9 additional subjects. Subjects enrolled in the second phase of the study will also receive a second injection of NanoPac at the same dose 12 weeks after the first NanoPac injection.

Intracystic Injection of NanoPac® in Subjects With Mucinous Cystic Pancreatic Neoplasms

A Trial Evaluating Escalating Doses and the Safety of Intracystic Injection of NanoPac® in Subjects With Mucinous Cystic Pancreatic Neoplasms

Treatment Emergent Adverse Events will include laboratory assessments, physical examination findings, and vital signs.

Cyst volume at screening will be compared with the volume at Weeks 12 and 24 (or early termination).

US Biotest, Inc.

NanOlogy, LLC

Single intracystic injection of NanoPac® at a dose of 6 mg/mL in a volume sufficient to fill the cyst, at least equal to the amount of cyst fluid aspirated

NanoPac®: NanoPac® (Sterile Nanoparticulate Paclitaxel) for intracystic injection via endoscopic ultrasound-guided injection (EUS-FNI)

Dose Escalation: NanoPac® 6 mg/mL

Single intracystic injection of NanoPac® at a dose of 10 mg/mL in a volume sufficient to fill the cyst, at least equal to the amount of cyst fluid aspirated

NanoPac®: NanoPac® (Sterile Nanoparticulate Paclitaxel) for intracystic injection via endoscopic ultrasound-guided injection (EUS-FNI)

Dose Escalation: NanoPac® 10 mg/mL

Single intracystic injection of NanoPac® at a dose of 15 mg/mL in a volume sufficient to fill the cyst, at least equal to the amount of cyst fluid aspirated

NanoPac®: NanoPac® (Sterile Nanoparticulate Paclitaxel) for intracystic injection via endoscopic ultrasound-guided injection (EUS-FNI)

Dose Escalation: NanoPac® 15 mg/mL

Intracystic injection of NanoPac®. The dose administered in the second phase will be determined during the dose escalation phase. Subjects will receive up to two NanoPac® injections, with the second injection administered 12 weeks after the first injection.

NanoPac®: NanoPac® (Sterile Nanoparticulate Paclitaxel) for intracystic injection via endoscopic ultrasound-guided injection (EUS-FNI)

Second Phase: NanoPac® 15 mg/mL (Up to Two Injections)

Total

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Body Mass Index (BMI) (kg/m2)

All enrolled subjects (n=20) who received at least one NanoPac injection (n=19) were designated as the Safety Population, and included in the analysis population for all outcome analyses. The subject who withdrew consent prior to any NanoPac treatment is not included in the analysis population.

Gere S. diZerega, MD

Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability)

Screening

Week 12

Week 24/EOS

In the dose escalation phase, baseline imaging data for the measurement of cyst diameters and calculation of cyst volume was available in all subjects. At Week 12, 18 of 19 subjects had three cyst diameters available for analyses. At Week 24, 17 of 19 subjects had three cyst diameters available for analyses.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Contrast Enhanced Ultrasound and Molecular Analysis in the Diagnosis of Pancreatic Cyst	NCT03740360	Pancreatic Cyst		18 Years -	Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Endoscopic Ultrasound-guided Ethanol Injection of Pancreatic Cystic Neoplasms	NCT02158039	Neoplasms, Cyst...	Ethanol Lidocaine	18 Years -	Mayo Clinic
Endoscopic Ultrasound-guided Ethanol Injection of Pancreatic Cystic Neoplasms	NCT02158039	Neoplasms, Cyst...	Ethanol Lidocaine	18 Years -	Mayo Clinic
Vitamin E δ-Tocotrienol Administered to Subjects With Resectable Pancreatic Exocrine Neoplasia	NCT00985777	Pancreatic Neop...	Vitamin E δ-Toc...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
UCSF PANC Cyst Registry	NCT04291651	Pancreatic Cyst Pancreatic Neop... Pancreatic Canc... Pancreatic Dise... Pancreatic Intr... Intraductal Pap... Pancreatic Duct... Mucinous Cyst	Survey	18 Years -	University of California, San Francisco
Intracystic Injection of NanoPac® in Subjects With Mucinous Cystic Pancreatic Neoplasms	NCT03188991	Pancreatic Muci...	NanoPac®	18 Years -	NanOlogy, LLC

Spots Global Cancer Trial Database for mucinous cystic neoplasm