Trial of NanoPac® in Subjects With Locally Advanced Pancreatic Adenocarcinoma

• ClinicalTrials.gov Identifier: NCT03077685
• Recruitment Status: Completed
• First Posted: March 13, 2017
• Last Update Posted: November 8, 2023
• Sponsor: NanOlogy, LLC
• Collaborator: US Biotest, Inc.
• Information provided by (Responsible Party): NanOlogy, LLC

Tracking Information

• First Submitted Date: February 28, 2017
• First Posted Date: March 13, 2017
• Last Update Posted Date: November 8, 2023
• Actual Study Start Date: December 1, 2017
• Actual Primary Completion Date: March 15, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 27, 2020)

Incidence of Treatment Emergent Adverse Events (safety and tolerability) [ Time Frame: Up to 6 (six) months after NanoPac® injection ]

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

Original Primary Outcome Measures (submitted: March 7, 2017)

Incidence of Treatment Emergent Adverse Events (safety and tolerability) [ Time Frame: Up to 3 (three) months after NanoPac injection ]

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

Current Secondary Outcome Measures (submitted: October 27, 2020)

• Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) of NanoPac® [ Time Frame: Up to 6 (six) months after NanoPac® injection ]
  Pharmacokinetic (PK) samples will be taken on Day 1 prior to injection, and at 1, 2, 4, 6, and 24 hours post-injection, and again at all study visits post-injection
• Pharmacokinetics: Peak plasma concentration (Cmax) of NanoPac® [ Time Frame: Up to 6 (six) months after NanoPac® injection ]
  Pharmacokinetic (PK) samples will be taken on Day 1 prior to injection, and at 1, 2, 4, 6, and 24 hours post-injection, and again at all study visits post-injection
• Pharmacokinetics: Time at which peak plasma concentration is observed (Tmax) of NanoPac® [ Time Frame: Up to 6 (six) months after NanoPac® injection ]
  Pharmacokinetic (PK) samples will be taken on Day 1 prior to injection, and at 1, 2, 4, 6, and 24 hours post-injection, and again at all study visits post-injection
• Tumor Response (RECIST) [ Time Frame: Baseline and every 3 (three) months after NanoPac® injection, up to 12 months ]
  Tumor burden at 3 months after NanoPac® injection will be compared with baseline tumor burden.
• Change in pain score [ Time Frame: Baseline and 3 (three) months after NanoPac® injection ]
  Pain scores will be measured using a visual analog scale
• Change in tumor markers [ Time Frame: Baseline, 3 (three) months, and 6 (six) months after NanoPac® injection ]
  Tumor markers measured will include CEA and CA19-9

Original Secondary Outcome Measures (submitted: March 7, 2017)

• Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) of NanoPac [ Time Frame: Up to 3 (three) months after NanoPac injection ]
  Pharmacokinetic (PK) samples will be taken on Day 1 prior to injection, and at 1, 2, 4, 8, and 24 hours post-injection, and again at all study visits post-injection
• Pharmacokinetics: Peak plasma concentration (Cmax) of NanoPac [ Time Frame: Up to 3 (three) months after NanoPac injection ]
  Pharmacokinetic (PK) samples will be taken on Day 1 prior to injection, and at 1, 2, 4, 8, and 24 hours post-injection, and again at all study visits post-injection
• Pharmacokinetics: Time at which peak plasma concentration is observed (Tmax) of NanoPac [ Time Frame: Up to 3 (three) months after NanoPac injection ]
  Pharmacokinetic (PK) samples will be taken on Day 1 prior to injection, and at 1, 2, 4, 8, and 24 hours post-injection, and again at all study visits post-injection
• Tumor Response (RECIST) [ Time Frame: Baseline and 3 (three) months after NanoPac injection ]
  Tumor burden at 3 months after NanoPac injection will be compared with baseline tumor burden.
• Change in pain score [ Time Frame: Baseline and 3 (three) months after NanoPac injection ]
  Pain scores will be measured using a visual analog scale
• Change in tumor markers [ Time Frame: Baseline and 3 (three) months after NanoPac injection ]
  Tumor markers measured will include CEA and CA19-9

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial of NanoPac® in Subjects With Locally Advanced Pancreatic Adenocarcinoma
• Official Title: Phase IIa Trial Evaluating the Safety of Intratumoral Injection of NanoPac® in Subjects With Locally Advanced Pancreatic Adenocarcinoma
• Brief Summary: Open-label, dose-escalating, Phase IIa trial of NanoPac® to treat subjects with locally advanced pancreatic adenocarcinoma via direct intratumoral injection.

Detailed Description

In this open-label, dose-escalating, Phase IIa trial, subjects with locally advanced pancreatic adenocarcinoma will receive intratumoral (ITU) NanoPac® (Sterile Nanoparticulate Paclitaxel) via endoscopic ultrasound-guided direct injection.

Subjects will be enrolled in sequential cohorts of NanoPac® at escalating doses, at a volume based on up to 20% of calculated tumor volume (with a maximum injection volume of 5 mL per subject). 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 most suitable for further evaluation, defined as the highest dose with an acceptable safety and tolerability profile as determined by the Data Safety Monitoring Board (DSMB), will be the dose used in the second phase of the study which will enroll 22 additional subjects who will receive two injections of NanoPac® at the same dose one month apart. In the third phase of the study, up to 30 subjects will receive up to four injections of NanoPac at the same dose, one month apart.

Plasma samples will be taken at various time points on the day of NanoPac® injection as well as once at each of the study visits, to characterize the pharmacokinetics (PK) of intratumoral NanoPac®.

Subjects will be followed for 12 months after NanoPac® injection for safety, overall survival (OS), progression-free survival (PFS), CA-19-9 levels, carcinoembryonic antigen (CEA) levels, reduction in pain, and tumor response to therapy (as shown by imaging).

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Open-label, dose-escalating, Phase IIa trial. Subjects will be enrolled in sequential cohorts of NanoPac® at a volume up to 20% of tumor volume (maximum injection volume of 5 mL per subject). Each cohort will have 3 subjects, with cohorts enrolled sequentially starting at the lowest concentration. Following DSMB review of the cohort data, the next cohort may begin enrolling. The highest dose with an acceptable safety and tolerability profile will be the dose used in the second phase of the study which will enroll 22 additional subjects to receive 2 NanoPac® injections one month apart and 30 additional subjects to receive 4 NanoPac® injections one month apart.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Locally Advanced Pancreatic Adenocarcinoma

Intervention

Drug: NanoPac®

Subjects with locally advanced pancreatic adenocarcinoma will receive intratumoral (ITU) NanoPac® (Sterile Nanoparticulate Paclitaxel) via endoscopic ultrasound-guided direct injection.

Other Name: Paclitaxel

Study Arms

• Experimental: Dose Escalation: NanoPac® 6 mg/mL
  Intratumorally injected NanoPac® at a volume of up to 20% tumor volume
  Intervention: Drug: NanoPac®
• Experimental: Dose Escalation: NanoPac® 10 mg/mL
  Intratumorally injected NanoPac® at a volume of up to 20% tumor volume
  Intervention: Drug: NanoPac®
• Experimental: Dose Escalation: NanoPac® 15 mg/mL
  Intratumorally injected NanoPac® at a volume of up to 20% tumor volume
  Intervention: Drug: NanoPac®
• Experimental: Second Phase: NanoPac® at Best Dose
  Intratumorally injected NanoPac® at a volume of up to 20% tumor volume. The dose administered in the second phase will be determined during the dose escalation phase. Subjects will receive two NanoPac® administrations, with the second injection administered one month after the first injection.
  Intervention: Drug: NanoPac®
• Experimental: Third Phase: NanoPac® at Best Dose
  Intratumorally injected NanoPac® at a volume of up to 20% tumor volume. The dose administered in the third phase will be determined during the dose escalation phase. Subjects will receive four NanoPac® administrations, with the injections administered one month apart.
  Intervention: Drug: NanoPac®

Publications *

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
• Taxol® (paclitaxel) Injection Package Insert. Bristol-Myers Squibb Company. Rev July 2011.
• ABRAXANE Package Insert. Celgene Company. Rev July 2015.
• Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 7, 2023): 54
• Original Estimated Enrollment (submitted: March 7, 2017): 30
• Actual Study Completion Date: March 15, 2023
• Actual Primary Completion Date: March 15, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Signed informed consent;
• Age ≥18 years;
• Histologically/cytologically confirmed locally advanced pancreatic adenocarcinoma; at least one lesion with a diameter of at least 1.5 cm but no more than 6 cm as documented via imaging (within 6 weeks of Screening);
• Subject not a candidate for surgery;
• Completion of at least one standard of care IV chemotherapy course for subjects in the dose escalation phase of the study. IV chemotherapy will be initiated prior to first NanoPac injection for subjects in the second and third phases. Hematologic recovery must be confirmed prior to study entry;
• Performance Status (ECOG) 0-1 at study entry;
• Life expectancy of at least 3 months;

• Adequate marrow, liver, and renal function at study entry:

  • ANC ≥ 1.5 x 109/L
  • Hemoglobin ≥ 9.5 grams/dL
  • Platelets ≥ 75 x 109/L
  • Total bilirubin ≤ 1.5x institutional ULN
  • AST/ ALT ≤ 2.5x institutional ULN
  • Creatinine ≤ 1.5x institutional ULN
• Effective contraception if the risk of conception exists.

Exclusion Criteria:

• Thrombotic or embolic events;
• Acute or subacute intestinal occlusion;
• History of inflammatory bowel disease;
• Known hypersensitivity to study drugs;
• Known drug or alcohol abuse;
• Pregnant or breastfeeding women;
• Previous or concurrent history of non-pancreatic malignancy except for non-melanoma skin cancer.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03077685
• Other Study ID Numbers: NANOPAC-2016-05
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: NanOlogy, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: NanOlogy, LLC
• Original Study Sponsor: Same as current
• Collaborators: US Biotest, Inc.

Investigators

• Study Director: Shelagh Verco, PhD; Vice President, Clinical Development, US Biotest, Inc

• PRS Account: NanOlogy, LLC
• Verification Date: November 2023