Phase I - Escalating Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Locally Advanced Adenocarcinoma of the Pancreas, and a Single Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Non-operable Adenocarcinoma of the Pancreas
Phase 0 - Open label, Single dose study of siG12D LODER in Patients with operable adenocarcinoma of the pancreas.
The primary endpoint:
To assess efficacy and local distribution of siRNA out of eight high dose siG12D LODERs in patients diagnosed with operable adenocarcinoma of the pancreas.
The Secondary endpoint:
Short term tolerability and safety assessment
Phase I - This study is designed to investigate the safety of siG12D LODER (Local Drug EluteR) in patients diagnosed with adenocarcinoma of the pancreas.
The primary endpoint:
To asses efficacy of siG12D LODER and local distribution in non-operable patients by histopathology measurements, local distribution by RNA analysis.
To define the dose-limiting toxicities (DLT)
The Secondary endpoint
- To determine the recommended Phase II dose (RP2D)
- To define and maximum tolerated dose (MTD)
- In the event of surgery, assessment of siG12D LODER local distribution and efficacy will be based on histopathology measurements and RNA analysis.
- Progression free survival - only by long term follow-up
|Pancreatic Ductal Adenocarcinoma Pancreatic Cancer||Drug: siG12D LODER||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I - Escalating Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Locally Advanced Adenocarcinoma of the Pancreas, and a Single Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Non-operable Adenocarcinoma of the Pancreas|
- Number of Participants with Adverse Events [ Time Frame: Phase 0 - 6 weeks, Phase I - 2 months ]
|Study Start Date:||January 2011|
|Study Completion Date:||December 2013|
|Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Drug: siG12D LODER
Phase 0 - subjects diagnosed with an operable adenocarcinoma of the pancreas will have 8 siG12D LODER placed in tumor. The siG12D LODER will be placed in the subject's tumor using an EUS biopsy needle.
Phase I - subjects diagnosed with locally non-operable advanced adenocarcinoma of the pancreas. These subjects will have one of three different siG12D LODERs dose levels placed in tumor - Either 1 siG12D LODER, 2 siG12D LODERs or 8 siG12D LODERs. The siG12D LODER/s will be placed in the subject's tumor using an EUS biopsy needle.
The investigational agent siG12D LODER (Local Drug EluteR) is a miniature biodegradable polymeric matrix that encompasses anti KRASG12D siRNA (siG12D) drug, designed to release the drug regionally within a pancreatic tumor, at a prolonged rate of 12-16 weeks.
The majority of pancreatic ductal adenocarcinomas involve mutations in the KRAS oncogene (the most common is G12D), therefore stable administration of KRASG12D siRNA has the potential to silence and lead to apoptosis of such cancer cells and thereby slow and even halt the tumor growth.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01188785
|Shaare Zedek Medical Center|
|Jerusalem, Israel, 91031|
|Hadassah Medical Organization|
|Jerusalem, Israel, 91120|
|Sheba Medical Center|
|Ramat Gan, Israel, 52621|
|Principal Investigator:||Ayala Hubert, MD||Hadassah Medical Organization|
|Principal Investigator:||Talya Golan, MD||Sheba Medical Center|
|Principal Investigator:||Amiel Segal, MD||Shaare Zedek Medical Center|