Intracystic Injection of NanoPac® 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).

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

Primary outcomes

• Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) [Up to 6 (six) months after first NanoPac® injection]: Treatment Emergent Adverse Events will include laboratory assessments, physical examination findings, and vital signs.

Secondary outcomes

• Cyst Volume Response [Screening and 6 (six) months after first NanoPac® injection]: Cyst volume at screening will be compared with the volume at Weeks 12 and 24 (or early termination).

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) (Primary), Count of participants, Participants: Dose Escalation: NanoPac® 6 mg/mL 3; Dose Escalation: NanoPac® 10 mg/mL 3; Dose Escalation: NanoPac® 15 mg/mL 3; Second Phase: NanoPac® 15 mg/mL (Up to Two Injections) 9
• Cyst Volume Response (Secondary), Mean, mL: Dose Escalation: NanoPac® 6 mg/mL 7.770 +/- 3.283; Dose Escalation: NanoPac® 10 mg/mL 4.810 +/- 5.109; Dose Escalation: NanoPac® 15 mg/mL 10.960 +/- 8.484; Second Phase: NanoPac® 15 mg/mL (Up to Two Injections) 11.442 +/- 8.132

Adverse events

Time frame: AEs were collected at all study visits from the time of dosing (Day 1 through Week 24).

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2019-09-03)
• Statistical Analysis Plan (PDF, 2020-08-21)