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A Phase II Study of siG12D LODER in Combination With Chemotherapy in Patients With Unresectable Locally Advanced Pancreatic Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2016 by Silenseed Ltd
Sponsor:
Information provided by (Responsible Party):
Silenseed Ltd
ClinicalTrials.gov Identifier:
NCT01676259
First received: August 28, 2012
Last updated: November 9, 2016
Last verified: October 2016
  Purpose

In this Phase II study a single dose 2.8 mg (eight 0.35 mg siG12D-LODERs) will be administered to patients with unresectable locally advanced pancreatic cancer combined with chemotherapy treatment.

Primary Outcome:

- Progression-free survival (PFS) in the study population.


Condition Intervention Phase
Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer
Drug: siG12D-LODER
Drug: Gemcitabine+nab-Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Open Label Study of Single Dose siG12D LODER in Combination With Chemotherapy in Patients With Unresectable Locally Advanced Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Silenseed Ltd:

Primary Outcome Measures:
  • Progression-free survival (PFS) in the study population [ Time Frame: One year ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: February 2017
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Chemotherapy
Gemcitabine+nab-Paclitaxel
Drug: Gemcitabine+nab-Paclitaxel
Gemcitabine+nab-Paclitaxel
Other Name: Chemotherapy
Experimental: siG12D-LODER + chemotherapy
Eight siG12D-LODER+(Gemcitabine+nab-Paclitaxel)
Drug: siG12D-LODER
The implantation of siG12D-LODERs is selected to meet current gastroenterology endoscopic ultrasound (EUS) biopsy procedures, proved to be highly effective and safe.
Drug: Gemcitabine+nab-Paclitaxel
Gemcitabine+nab-Paclitaxel
Other Name: Chemotherapy

Detailed Description:

In this Phase II study a single dose 2.8 mg (eight 0.35 mg siG12D-LODERs) will be administered to patients with unresectable LAPC combined with chemotherapy treatment (Gemcitabine+nab-Paclitaxel). This will be the first study to assess the response rate of the siG12D-LODER in patients with unresectable LAPC. The study is of a two-arm design with one arm receiving siG12D-LODER + chemotherapy, while the other arm receiving only chemotherapy.

The investigational agent siG12D-LODER is a miniature biodegradable bio polymeric matrix that encompasses the drug, designed and produced by Silenseed Ltd. The implantation of LODERs is selected to meet current gastroenterology endoscopic ultrasound (EUS) biopsy procedures, proved to be highly effective and safe.

siG12D-LODER has been studied in the escalating dose Phase I study of 15 patients, and results showed a high safety and tolerability profiles, with no single DLT.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who provide written informed consent to participate in the study
  • Men and women patients 18 years of age and up
  • Have an unresectable, locally advanced pancreatic cancer (AJCC stage III). (Excluded: resectable and borderline resectable patients are ineligible per NCCN criteria)
  • Allocated to receive Gemcitabine + nab-Paclitaxel as first line treatment.
  • Have a target tumor that is accessible for intratumoral administration by PTA (Percutaneous transluminal approach) or EUS (Endoscopic Ultrasound) guidance as determined by the radiologist/gastroenterologist performing the PTA/EUS injection.
  • Have an ECOG performance status of ≤ 1
  • If female and of childbearing potential, have a negative serum or urine pregnancy test during screening. Agree to use 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 <1.6 mg/dL, INR < 1.5 U, absolute neutrophil count (ANC) > 1 x 109/L , platelets ≥ 100 x 109/L , hemoglobin ≥ 10 mg/dL, ALT and AST ≤ 3 x ULN, bilirubin ≤ 1.5 x ULN
  • Have measurable disease. Patients must have clinically and/or radiographically documented measurable primary disease according to RECIST 1.1. At least one site of disease must be unidimensionally measurable. All radiology scans must be performed within 28 days prior to registration

Exclusion Criteria:

  • Evidence of metastatic disease
  • Other malignancy that would interfere with the current intervention
  • Any evidence of ascites (beyond trace)
  • Bulky celiac adenopathy (≥2.5 cm) or nonadenocarcinoma histology.
  • Any prior therapy for the treatment of pancreatic malignancy (including chemotherapy, immunotherapy, vaccines, monoclonal antibodies, major surgery, or irradiation, whether conventional or investigational).
  • Prior therapy with any hypoxic cytotoxin (hypoxia-targeting drugs).
  • Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancers from which the subject has been disease-free for at least 2 years
  • Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation <90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause systemic or regional hypoxemia
  • History of clinically significant coagulopathy
  • Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
  • New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 4months prior to Day 1, unstable arrhythmia or symptomatic peripheral arterial vascular disease
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  • Subjects who participated in an investigational drug or device study within 28 days prior to study entry
  • Known active infection with HIV, hepatitis B virus, or hepatitis C virus
  • Females who are pregnant or breast-feeding
  • Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
  • Unwillingness or inability to comply with the study protocol for any reason
  • Participation in another clinical trial with drugs received within 3 months prior to dosing (calculated from the previous study's last dosing date).
  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: NCT01676259

Contacts
Contact: Sofia Muravnik +972-8-6286005 Sofia@silenseed.com

Locations
United States, Maryland
The Johns Hopkins Hospital Not yet recruiting
Baltimore, Maryland, United States, 21231
Principal Investigator: Daniel Laheru, MD         
United States, New York
The Mount Sinai Hospital Not yet recruiting
New York, New York, United States, 10029
Contact: Christopher J DiMaio, MD    212-241-7535    Christopher.DiMaio@mountsinai.org   
Principal Investigator: Christopher J DiMaio, MD         
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Contact: Eileen M O'Reilly, MD    646-888-4182    oreillye@mskcc.org   
Principal Investigator: Eileen M. O'Reilly, MD         
United States, Ohio
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States, 44195
Principal Investigator: Alok Khorana, MD         
Israel
Sheba Medical Center
Ramat Gan, Israel, 52621
Sponsors and Collaborators
Silenseed Ltd
Investigators
Principal Investigator: Eileen M O'Reilly, MD Memorial Sloan Kettering Cancer Center
Principal Investigator: Talia Golan, MD Sheba Medical Center
  More Information

Additional Information:
Responsible Party: Silenseed Ltd
ClinicalTrials.gov Identifier: NCT01676259     History of Changes
Other Study ID Numbers: SLSG12D-P2 
Study First Received: August 28, 2012
Last Updated: November 9, 2016
Health Authority: Israel: Ethics Commission

Keywords provided by Silenseed Ltd:
siRNA
RNA interference (RNAi)
Cancer
Pancreatic ductal adenocarcinoma
Locally Advanced Pancreatic cancer
Solid tumor
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
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on December 08, 2016