Trial Of NanoPac® In Subjects With Locally Advanced Pancreatic Adenocarcinoma

Study Overview

Trial 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.

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). During the first phase of the trial (dose escalation), 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 ITU 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).

Locally Advanced Pancreatic Adenocarcinoma

DRUG: NanoPac®

NANOPAC-2016-05

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2017-02-28	Results First Submitted 2024-03-19	Last Update Submitted that met QC Criteria 2024-06-19
First Submitted that Met QC Criteria 2017-03-07	Results First Submitted that Met QC Criteria 2024-06-19	Last Update Posted (ACTUAL) 2024-06-24
First Posted (ACTUAL) 2017-03-13	Results First Posted 2024-06-24	Last Verified 2024-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

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

Primary Outcome Measures	Measure Description	Time Frame
Number of Subjects With Treatment Emergent Adverse Events (Safety and Tolerability)	Treatment Emergent Adverse Events will include laboratory assessments, physical examination findings, and vital signs.	Up to Week 24 for Dose Escalation subjects; up to Week 28 for Second Phase subjects; up to 9 Months for Third Phase subjects.

Secondary Outcome Measures	Measure Description	Time Frame
Target Tumor Assessment	Response was determined using RECIST 1.1 parameters (complete response, partial response, stable disease, progressive disease, unevaluable) for the treated lesion in all groups.	Week 24
Plasma Paclitaxel Concentration (pg/mL)	Plasma paclitaxel concentrations were analyzed in the dose escalation phase on Day 1 prior to injection and at 1, 2, 4, 6, and 24 hours after NanoPac injection, as well as at all other study visits. In the second and third phases, plasma paclitaxel concentrations were analyzed on Day 1 prior to NanoPac injection, and at 1 and 2 hours post NanoPac injection on all injection occasions, and at all study visits.	Day 1 and Week 24
Pain (Visual Analog Scale) Score	The visual analog scale (VAS) ranks pain from numbers 0 (no pain) to 10 (most pain). Lower scores mean a better outcome.	Day 1 (pre-injection) and Week 24
Serum CA19-9 Level	CA19-9 is a tumor marker for pancreatic cancer. Serum CA19-9 levels were assessed at all study visits.	Day 1 (Pre-Injection) and Week 24
Serum CEA Levels	Carcinoembryonic antigen (CEA) is a tumor marker for pancreatic cancer.	Day 1 (Pre-Injection) and Week 24

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

US Biotest, Inc.

Investigators

STUDY_DIRECTOR: Shelagh Verco, PhD, Vice President, Clinical Development, NanOlogy, LLC

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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.
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.
Sharma NR, Lo SK, Hendifar A, Othman MO, Patel K, Mendoza-Ladd A, Verco S, Maulhardt HA, Verco J, Wendt A, Marin A, Schmidt CM, diZerega G. Response of Locally Advanced Pancreatic Cancer to Intratumoral Injection of Large Surface Area Microparticle Paclitaxel: Initial Report of Safety and Clinical Outcome. Pancreas. 2023 Mar 1;52(3):e179-e187. doi: 10.1097/MPA.0000000000002236.

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