Trial of NanoPac® in Subjects With Locally Advanced Pancreatic Adenocarcinoma

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

Detailed Description
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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).

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

Conditions
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Locally Advanced Pancreatic Adenocarcinoma

Intervention / Treatment
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* Drug: NanoPac®


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional 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)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic neoplasms, digestive system neoplasms, pancreatic diseases, digestive system diseases, pancreatic adenocarcinoma, pancreatic cancer