Trial of NanoPac® in Subjects With Locally Advanced Pancreatic Adenocarcinoma

NCT ID: NCT03077685

Last Updated: 2024-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2023-03-15

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). 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).

Conditions

Locally Advanced Pancreatic Adenocarcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation: NanoPac® 6 mg/mL

Intratumorally injected NanoPac® at a volume of up to 20% tumor volume

Group Type: EXPERIMENTAL

NanoPac®

Intervention Type: DRUG

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

Dose Escalation: NanoPac® 10 mg/mL

Intratumorally injected NanoPac® at a volume of up to 20% tumor volume

Group Type: EXPERIMENTAL

NanoPac®

Intervention Type: DRUG

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

Dose Escalation: NanoPac® 15 mg/mL

Intratumorally injected NanoPac® at a volume of up to 20% tumor volume

Group Type: EXPERIMENTAL

NanoPac®

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

NanoPac®

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

NanoPac®

Intervention Type: DRUG

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

Interventions

NanoPac®

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

Intervention Type: DRUG

Other Intervention Names

Paclitaxel

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

US Biotest, Inc.

INDUSTRY

Sponsor Role: collaborator

NanOlogy, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shelagh Verco, PhD

Role: STUDY_DIRECTOR

Vice President, Clinical Development, NanOlogy, LLC

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Parkview Cancer Institute

Fort Wayne, Indiana, United States

Texas Tech University Health Sciences Center

El Paso, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 19097774 (View on PubMed)

Taxol® (paclitaxel) Injection Package Insert. Bristol-Myers Squibb Company. Rev July 2011.

Reference Type: BACKGROUND

ABRAXANE Package Insert. Celgene Company. Rev July 2015.

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 24131140 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37782888 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

NANOPAC-2016-05

Identifier Type: -

Identifier Source: org_study_id