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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Pancreatic Mucinous-Cystic Neoplasm

Intervention / Treatment
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* Drug: NanoPac®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent; Patients over the age of 18; Recently confirmed mucinous cystic pancreatic neoplasm; may be confirmed by presence of mucin, cyst fluid carcinoembryonic antigen (CEA) above 192 U/L, or other reliable diagnostic means such as endomicroscopy; KRAS analysis may also be performed at the discretion of the Investigator; Unilocular cyst with diameter of at least 1.5 cm but no more than 4 cm; Normal hematologic, hepatic, and renal function at study entry; Appropriate steps taken to minimize or avoid the potential for pregnancy for subjects of child-bearing potential.* Note: A female patient is considered to be of childbearing potential unless she has had a hysterectomy, is at least one year postmenopausal or has undergone tubal ligation. For the purposes of this study, adequate birth control includes at least one medically approved and highly effective method of birth control, defined as those which result in a low failure rate (i.e., < 1% per year) when used consistently and correctly, such as implants, injectables and oral contraceptives combined with the use of condoms. Only male patients whose vasectomy has been confirmed by semen analysis at least 3 months after the vasectomy are allowed not to use acceptable contraceptive methods. Exclusion Criteria: Positive cytology indicating malignancy; Thrombotic or embolic events; Known hypersensitivity to study agent; Known drug or alcohol abuse; Pregnant or breastfeeding women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation: NanoPac® 6 mg/mL<br>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 | Drug: NanoPac®<br>* NanoPac® (Sterile Nanoparticulate Paclitaxel) for intracystic injection via endoscopic ultrasound-guided injection (EUS-FNI)<br>|
| Experimental: Dose Escalation: NanoPac® 10 mg/mL<br>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 | Drug: NanoPac®<br>* NanoPac® (Sterile Nanoparticulate Paclitaxel) for intracystic injection via endoscopic ultrasound-guided injection (EUS-FNI)<br>|
| Experimental: Dose Escalation: NanoPac® 15 mg/mL<br>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 | Drug: NanoPac®<br>* NanoPac® (Sterile Nanoparticulate Paclitaxel) for intracystic injection via endoscopic ultrasound-guided injection (EUS-FNI)<br>|
| Experimental: Second Phase: NanoPac® at Best Dose<br>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. | Drug: NanoPac®<br>* NanoPac® (Sterile Nanoparticulate Paclitaxel) for intracystic injection via endoscopic ultrasound-guided injection (EUS-FNI)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | Treatment Emergent Adverse Events will include laboratory assessments, physical examination findings, and vital signs. | Up to 6 (six) months after first NanoPac® injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cyst Volume Response | Cyst volume at screening will be compared with the volume at Weeks 12 and 24 (or early termination). | Screening and 6 (six) months after first NanoPac® injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cystic neoplasm, pancreatic cyst, pancreatic mucinous cyst, pancreatic neoplasms, digestive system neoplasms, pancreatic diseases, mucinous cystic neoplasm