Trial of NanoPac® in Subjects With Locally Advanced Pancreatic Adenocarcinoma

Phase IIa Trial Evaluating the Safety of Intratumoral Injection of NanoPac® in Subjects With Locally Advanced Pancreatic Adenocarcinoma

Open-label, dose-escalating, Phase IIa trial of NanoPac® to treat subjects with locally advanced pancreatic adenocarcinoma via direct intratumoral injection.

Study Overview

• Status: Completed
• Conditions: Locally Advanced Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: NanoPac®

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
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Parkview Cancer Institute
  • Texas
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Sciences Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: NanoPac® 6 mg/mL; Intratumorally injected NanoPac® at a volume of up to 20% tumor volume	Drug: NanoPac®; Subjects with locally advanced pancreatic adenocarcinoma will receive intratumoral (ITU) NanoPac® (Sterile Nanoparticulate Paclitaxel) via endoscopic ultrasound-guided direct injection.; Other Names: Paclitaxel
Experimental: Dose Escalation: NanoPac® 10 mg/mL; Intratumorally injected NanoPac® at a volume of up to 20% tumor volume	Drug: NanoPac®; Subjects with locally advanced pancreatic adenocarcinoma will receive intratumoral (ITU) NanoPac® (Sterile Nanoparticulate Paclitaxel) via endoscopic ultrasound-guided direct injection.; Other Names: Paclitaxel
Experimental: Dose Escalation: NanoPac® 15 mg/mL; Intratumorally injected NanoPac® at a volume of up to 20% tumor volume	Drug: NanoPac®; Subjects with locally advanced pancreatic adenocarcinoma will receive intratumoral (ITU) NanoPac® (Sterile Nanoparticulate Paclitaxel) via endoscopic ultrasound-guided direct injection.; Other Names: Paclitaxel
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.	Drug: NanoPac®; Subjects with locally advanced pancreatic adenocarcinoma will receive intratumoral (ITU) NanoPac® (Sterile Nanoparticulate Paclitaxel) via endoscopic ultrasound-guided direct injection.; Other Names: Paclitaxel
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.	Drug: NanoPac®; Subjects with locally advanced pancreatic adenocarcinoma will receive intratumoral (ITU) NanoPac® (Sterile Nanoparticulate Paclitaxel) via endoscopic ultrasound-guided direct injection.; Other Names: Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of 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 NanoPac® injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) of NanoPac®	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	Up to 6 (six) months after NanoPac® injection
Pharmacokinetics: Peak plasma concentration (Cmax) of NanoPac®	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	Up to 6 (six) months after NanoPac® injection
Pharmacokinetics: Time at which peak plasma concentration is observed (Tmax) of NanoPac®	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	Up to 6 (six) months after NanoPac® injection
Tumor Response (RECIST)	Tumor burden at 3 months after NanoPac® injection will be compared with baseline tumor burden.	Baseline and every 3 (three) months after NanoPac® injection, up to 12 months
Change in pain score	Pain scores will be measured using a visual analog scale	Baseline and 3 (three) months after NanoPac® injection
Change in tumor markers	Tumor markers measured will include CEA and CA19-9	Baseline, 3 (three) months, and 6 (six) months after NanoPac® injection

Collaborators and Investigators

• Sponsor: NanOlogy, LLC
• Collaborators: US Biotest, Inc.
• Investigators: Study Director: Shelagh Verco, PhD, Vice President, Clinical Development, US Biotest, Inc

Publications and helpful links

General 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.
• 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.
• Taxol® (paclitaxel) Injection Package Insert. Bristol-Myers Squibb Company. Rev July 2011.
• ABRAXANE Package Insert. Celgene Company. Rev July 2015.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Actual): March 15, 2023
• Study Completion (Actual): March 15, 2023

Study Registration Dates

• First Submitted: February 28, 2017
• First Submitted That Met QC Criteria: March 7, 2017
• First Posted (Actual): March 13, 2017

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: pancreatic adenocarcinoma; pancreatic cancer; pancreatic neoplasms; digestive system neoplasms; pancreatic diseases; digestive system diseases
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: NANOPAC-2016-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No