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
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.
- 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
- 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
- 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
- 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).