Clinical trial NCT03077685: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Locally Advanced Pancreatic Adenocarcinoma
Keywords: pancreatic neoplasms
digestive system neoplasms
pancreatic diseases
digestive system diseases
pancreatic adenocarcinoma
pancreatic cancer
Lead sponsor: NanOlogy, LLC
Sponsor class: INDUSTRY
Collaborators: name: US Biotest, Inc.
First posted: 2017-03-13
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Open-label, dose-escalating, Phase IIa trial.
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Number of Subjects With Treatment Emergent Adverse Events (Safety and Tolerability)
timeFrame: 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 outcomes:
measure: Target Tumor Assessment
timeFrame: Week 24
measure: Plasma Paclitaxel Concentration (pg/mL)
timeFrame: Day 1 and Week 24
measure: Pain (Visual Analog Scale) Score
timeFrame: Day 1 (pre-injection) and Week 24
measure: Serum CA19-9 Level
timeFrame: Day 1 (Pre-Injection) and Week 24
measure: Serum CEA Levels
timeFrame: Day 1 (Pre-Injection) and Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Fort Wayne
country: United States
facility: Parkview Cancer Institute
state: Indiana
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Vice President, Clinical Development, NanOlogy, LLC
name: Shelagh Verco, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Taxol® (paclitaxel) Injection Package Insert. Bristol-Myers Squibb Company. Rev July 2011.
citation: ABRAXANE Package Insert. Celgene Company. Rev July 2015.
citation: 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.