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 June 2014 by Silenseed Ltd
Sponsor:
Information provided by (Responsible Party):
Silenseed Ltd
ClinicalTrials.gov Identifier:
NCT01676259
First received: August 28, 2012
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

In this Phase II study a single dose 3,000µg (eight 375µg siG12DLODERs) 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 or FOLFIRINOX
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: 124
Study Start Date: January 2015
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Chemotherapy
Gemcitabine or FOLFIRINOX
Drug: Gemcitabine or FOLFIRINOX
Gemcitabine or FOLFIRINOX
Other Name: Chemotherapy
Experimental: siG12D LODER + chemotherapy
Eight siG12D LODER capsules + Gemcitabine or FOLFIRINOX
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 or FOLFIRINOX
Gemcitabine or FOLFIRINOX
Other Name: Chemotherapy

Detailed Description:

In this Phase II study a single dose 3,000µg (eight 375µg siG12DLODERs) will be administered to patients with unresectable LAPC combined with chemotherapy treatment (Gemcitabine or FOLFIRINOX). 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 ony chemotherapy.

The investigational agent siG12D LODER is a miniature biodegradable capsule 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 12 patients, and results showed a high safety and tolerability profiles, with no single DLT.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provide written informed consent and be between the ages of 18 and up.
  • Have an unresectable, locally advanced diagnosed adenocarcinoma of the pancreas. Or patients with a tumor who are not planning 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 in accordance with treating physician recommendation.
  • 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 an ECOG performance status of ≤ 1
  • 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 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, 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. Patients must have clinically and/or radiographically documented measurable disease. At least one site of disease must be unidimensionally measurable as follows:

CT-scan {> 10 mm} Lymph node short axis{ > 15 mm}

All radiology studies must be performed within 28 days prior to registration (35 days if negative).

Exclusion Criteria:

  • New York Heart Association (NYHA) Class III or IV, cardiac disease,myocardial infarction within 6 months prior to Day 1, unstable arrhythmia or symptomatic peripheral arterial vascular disease
  • Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months) or any other metastases
  • 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 5 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
  • Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  • Treatment of pancreatic cancer with surgery or radiation therapy prior to study entry
  • Prior therapy with an hypoxic cytotoxin
  • Subjects who participated in an investigational drug or device study within 28 days prior to study entry
  • Known 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
  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: Zivia Brunschwig +972-2-6743430 zivia@silenseed.com

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 Center
Principal Investigator: Talia 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: NCT01676259     History of Changes
Other Study ID Numbers: SLSG12D-P2
Study First Received: August 28, 2012
Last Updated: June 23, 2014
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:
Carcinoma, Ductal, Breast
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
Carcinoma, Ductal
Neoplasms, Ductal, Lobular, and Medullary
Breast Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on October 19, 2014