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 Operable Adenocarcinoma of the Pancreas

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Silenseed Ltd
ClinicalTrials.gov Identifier:
NCT01188785
First received: July 13, 2010
Last updated: February 11, 2013
Last verified: February 2013
  Purpose

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 Intervention Phase
Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer
Drug: siG12D LODER
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Parallel 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 Operable Adenocarcinoma of the Pancreas

Resource links provided by NLM:


Further study details as provided by Silenseed Ltd:

Primary Outcome Measures:
  • Number of Participants with Adverse Events [ Time Frame: Phase 0 - 6 weeks, Phase I - 2 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 22
Study Start Date: January 2011
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01188785

Locations
Israel
Hadassah Medical Organization
Jerusalem, Israel, 91120
Shaare Zedek Medical Center
Jerusalem, Israel, 91031
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:
No publications provided

Responsible Party: Silenseed Ltd
ClinicalTrials.gov Identifier: NCT01188785     History of Changes
Other Study ID Numbers: SLSG12D
Study First Received: July 13, 2010
Last Updated: February 11, 2013
Health Authority: Israel: Ministry of Health

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, Ductal, Breast
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
Carcinoma, Ductal
Neoplasms, Ductal, Lobular, and Medullary
Breast Neoplasms
Breast Diseases
Skin Diseases
Pancreatin
Pancrelipase
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014