Pancreatic Mucinous-Cystic Neoplasm
Conditions
Keywords
pancreatic cystic neoplasm, pancreatic cyst, pancreatic mucinous cyst, pancreatic neoplasms, digestive system neoplasms, pancreatic diseases, mucinous cystic neoplasm
Brief summary
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
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).
Interventions
DRUGNanoPac®
NanoPac® (Sterile Nanoparticulate Paclitaxel) for intracystic injection via endoscopic ultrasound-guided injection (EUS-FNI)
Sponsors
US Biotest, Inc.
NanOlogy, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation: NanoPac® 6 mg/mL 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) | 3 |
| Dose Escalation: NanoPac® 10 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) | 3 |
| Dose Escalation: NanoPac® 15 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) | 3 |
| Second Phase: NanoPac® 15 mg/mL (Up to Two Injections) 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) | 10 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Dose Escalation: NanoPac® 6 mg/mL | Dose Escalation: NanoPac® 10 mg/mL | Dose Escalation: NanoPac® 15 mg/mL | Second Phase: NanoPac® 15 mg/mL (Up to Two Injections) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 66.3 years STANDARD_DEVIATION 8.3 | 73.7 years STANDARD_DEVIATION 11.5 | 59.7 years STANDARD_DEVIATION 9.1 | 67.8 years STANDARD_DEVIATION 6.6 | 67.2 years STANDARD_DEVIATION 8.4 |
| Body Mass Index (BMI) (kg/m2) | 34.83 kg/m2 STANDARD_DEVIATION 11.71 | 27.93 kg/m2 STANDARD_DEVIATION 10.2 | 26.67 kg/m2 STANDARD_DEVIATION 3.43 | 32.82 kg/m2 STANDARD_DEVIATION 7.17 | 31.39 kg/m2 STANDARD_DEVIATION 7.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 3 Participants | 7 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 3 Participants | 8 Participants | 15 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 2 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 10 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 9 / 10 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 1 / 3 | 3 / 10 |
Outcome results
Primary
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.
Time frame: Up to 6 (six) months after first NanoPac® injection
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: NanoPac® 6 mg/mL | Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | 3 Participants |
| Dose Escalation: NanoPac® 10 mg/mL | Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | 3 Participants |
| Dose Escalation: NanoPac® 15 mg/mL | Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | 3 Participants |
| Second Phase: NanoPac® 15 mg/mL (Up to Two Injections) | Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | 9 Participants |
Secondary
Cyst Volume Response
Cyst volume at screening will be compared with the volume at Weeks 12 and 24 (or early termination).
Time frame: Screening and 6 (six) months after first NanoPac® injection
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: NanoPac® 6 mg/mL | Cyst Volume Response | Screening | 7.770 mL | Standard Deviation 3.283 |
| Dose Escalation: NanoPac® 6 mg/mL | Cyst Volume Response | Week 24/EOS | 4.140 mL | Standard Deviation 3.92 |
| Dose Escalation: NanoPac® 6 mg/mL | Cyst Volume Response | Week 12 | 5.710 mL | Standard Deviation 3.892 |
| Dose Escalation: NanoPac® 10 mg/mL | Cyst Volume Response | Screening | 4.810 mL | Standard Deviation 5.109 |
| Dose Escalation: NanoPac® 10 mg/mL | Cyst Volume Response | Week 24/EOS | 4.383 mL | Standard Deviation 0.521 |
| Dose Escalation: NanoPac® 10 mg/mL | Cyst Volume Response | Week 12 | 3.453 mL | Standard Deviation 2.188 |
| Dose Escalation: NanoPac® 15 mg/mL | Cyst Volume Response | Week 12 | 9.633 mL | Standard Deviation 9.284 |
| Dose Escalation: NanoPac® 15 mg/mL | Cyst Volume Response | Screening | 10.960 mL | Standard Deviation 8.484 |
| Dose Escalation: NanoPac® 15 mg/mL | Cyst Volume Response | Week 24/EOS | 8.533 mL | Standard Deviation 7.183 |
| Second Phase: NanoPac® 15 mg/mL (Up to Two Injections) | Cyst Volume Response | Screening | 11.442 mL | Standard Deviation 8.132 |
| Second Phase: NanoPac® 15 mg/mL (Up to Two Injections) | Cyst Volume Response | Week 24/EOS | 11.138 mL | Standard Deviation 11.931 |
| Second Phase: NanoPac® 15 mg/mL (Up to Two Injections) | Cyst Volume Response | Week 12 | 12.293 mL | Standard Deviation 10.755 |