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

NCT01188785 | Completed Phase 1 DMC

• 1 other identifier: SLSG12D
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

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

Conditions

Pancreatic Ductal Adenocarcinoma; Pancreatic Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events

  Phase 0 - 6 weeks, Phase I - 2 months

Study Arms (1)

1 arm

EXPERIMENTAL

SOC + siG12D LODER

Drug: siG12D LODER

Interventions

siG12D LODER DRUG

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.

1 arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Silenseed Ltd: lead

Study Sites (3)

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

Hadassah Medical Organization

Jerusalem, 91120, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Related Publications (1)

• 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.

  PMID: 26009994 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Ayala Hubert, MD

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

• Talya Golan, MD

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

• Amiel Segal, MD

  Shaare Zedek Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2010
• First Posted: August 25, 2010
• Study Start: January 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 9, 2019

Record last verified: 2014-11

Locations

IL (3)