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

• ClinicalTrials.gov Identifier: NCT01188785
• Recruitment Status: Completed
• First Posted: August 25, 2010
• Last Update Posted: April 9, 2019
• Sponsor: Silenseed Ltd
• Information provided by (Responsible Party): Silenseed Ltd

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Pancreatic Ductal Adenocarcinoma; Pancreatic Cancer	Drug: siG12D LODER	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: January 2011
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

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-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.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Adverse Events [ Time Frame: Phase 0 - 6 weeks, Phase I - 2 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Phase 0:

Provide written informed consent and be between the ages of 18 and up, inclusive.

• 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.

Phase I

• 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.

Exclusion Criteria:

Phase 0:

• 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.

Phase I:

• 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.

Contacts and Locations

Locations

Israel

Shaare Zedek Medical Center

Jerusalem, Israel, 91031

Hadassah Medical Organization

Jerusalem, Israel, 91120

Sheba Medical Center

Ramat Gan, Israel, 52621

Sponsors and Collaborators

Silenseed Ltd

Investigators

• 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

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Silenseed Ltd
• ClinicalTrials.gov Identifier: NCT01188785
• Other Study ID Numbers: SLSG12D
• First Posted: August 25, 2010
• Last Update Posted: April 9, 2019
• Last Verified: November 2014

Keywords provided by Silenseed Ltd:

siRNA; RNA interference (RNAi); Cancer; Pancreatic ductal adenocarcinoma; Pancreatic cancer; Solid tumor; Operable pancreatic ductal adenocarcinoma; Non operable pancreatic ductal adenocarcinoma

Additional relevant MeSH terms:

Adenocarcinoma; Pancreatic Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases