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

Study Overview

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 1. To determine the recommended Phase II dose (RP2D) 2. To define and maximum tolerated dose (MTD) 3. In the event of surgery, assessment of siG12D LODER local distribution and efficacy will be based on histopathology measurements and RNA analysis. 4. Progression free survival - only by long term follow-up

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.

Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer

DRUG: siG12D LODER

SLSG12D

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 2010-07-13	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2019-04-07
First Submitted that Met QC Criteria 2010-08-24	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2019-04-09
First Posted (ACTUAL) 2010-08-25	Results First Posted N/A	Last Verified 2014-11

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:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 1 arm SOC + siG12D LODER	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-o

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 1 arm

SOC + siG12D LODER

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-o

Primary Outcome Measures	Measure Description	Time Frame
Number of Participants with Adverse Events		Phase 0 - 6 weeks, Phase I - 2 months

Secondary Outcome Measures	Measure Description	Time Frame

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:

Patient that is diagnosed as respectable locally pancreatic tumor
Have a target tumor accessible for intratumoral administration by EUS (Endoscopic Ultrasound) guidance as determined by the physician performing the EUS guided LODER insertion.
Have a Karnofsky performance status of ≥ 70%.
Have a life expectancy of >= 3 months.
If female and of child-bearing potential, have a negative serum pregnancy test during screening.
Agree to use of a barrier method of contraception if sexually active (both men and women) from the time of administration of the first treatment and for at least 8 weeks after treatment.
Have serum creatinine < 2.0 mg/dL, , PT, - INR < 1.5 absolute neutrophil count (ANC) > 1,000 x 103 cells/mL, platelets ≥ 75,000/mL, and hemoglobin >= 10 mg/dL.
Have screening procedures completed within 2 weeks of starting treatment.
No other malignancy present that would interfere with the current intervention.
Have measurable disease.

Provide written informed consent and be between the ages of 18 and up.
Have an unresectable, locally advanced diagnosed or highly suspected adenocarcinoma of the pancreas. Or patients with a tumor and are not planed to undergo surgery due to a high surgical risk (e.g. coagulopathy or severe congestive heart failure).
Allocated to receive standard of care chemo as first line treatment.
Have a target tumor that is accessible for intratumoral administration by PTA or EUS guidance as determined by the radiologist/gastroenterologist performing the PTA/EUS injection.
Have a Karnofsky performance status of ≥ 70%.
Have a life expectancy of >= 3 months.
If female and of child-bearing potential, have a negative serum pregnancy test during screening.
Agree to use of a barrier method of contraception if sexually active (both men and women) from the time of administration of the first treatment and for at least 8 weeks after treatment.
Have serum creatinine < 2.0 mg/dL, PT - INR < 1.5, absolute neutrophil count (ANC) > 1,000 x 103 cells/mL, platelets ≥ 75,000/mL, and hemoglobin >= 10 mg/dL.
Have screening procedures completed within 4 weeks of starting treatment.
No other malignancy present that would interfere with the current intervention.
Have measurable disease.

Have distant metastasis spread (such as liver or lung, or lymph nodes metastases), peritoneal spread or malignant sites.
Have clinically significant pancreatitis within 12 weeks of treatment.
If female, be breast feeding.
Have a medical condition contraindicated for both percutaneous- and endoscopic- guided delivery or any intercurrent medical illness or other medical condition that would in the judgment of the investigator compromise patient safety or the objectives of the study.
Have a history of bleeding coagulopathy.
Have participated in any therapeutic research study within the last 4 weeks.

Have distant metastatic spread (such as liver, lung, or lymph nodes metastases), peritoneal spread or malignant sites.
Have clinically significant pancreatitis within 12 weeks of treatment.
If female, be breast feeding.
Have a medical condition contraindicated for both percutaneous- and endoscopic- guided delivery or any intercurrent medical illness or other medical condition that would in the judgment of the investigator compromise patient safety or the objectives of the study.
Have a history of bleeding coagulopathy.
Have participated in any therapeutic research study within the last 4 weeks.

Collaborators and Investigators

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

Investigators

PRINCIPAL_INVESTIGATOR: Ayala Hubert, MD, Hadassah Medical Organization

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

Golan T, Khvalevsky EZ, Hubert A, Gabai RM, Hen N, Segal A, Domb A, Harari G, David EB, Raskin S, Goldes Y, Goldin E, Eliakim R, Lahav M, Kopleman Y, Dancour A, Shemi A, Galun E. RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients. Oncotarget. 2015 Sep 15;6(27):24560-70. doi: 10.18632/oncotarget.4183.

Learn

Resources

PatientS

Caregivers

Clinical Trial Record