Efficacy and Safety of BC-819 and Gemcitabine in Patients With Locally Advanced Pancreatic Adenocarcinoma
Condition: Pancreas, Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Biological/Vaccine: BC-819
Intervention description: Post screening and prior to randomization, all patients will receive gemcitabine by IV infusion at a dose of 1000mg/m2 once weekly for four weeks. They may also enter the study if they received up to 4 doses of gemcitabine before entering the study. In this case, they will be randomized immediately provided there is no evidence of disease progression.
After randomization patients will receive 6 weekly IV infusions of gemcitabine at a dose of 1000mg/m2 + 7 intratumoral injections of BC-819 (8 mg or 12 mg according to allocations by randomization)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pancreatic cancer; Gemcitabine; BC-819; Adenocarcinoma; Resectable; H19 gene; DTA-H19; BioCancell; inodiftagene vixteplasmid

Summary:

      This is a multicenter, open label, randomized, phase 2b study, designed to evaluate the
      safety and efficacy of patients with locally advanced pancreatic adenocarcinoma following
      intratumoral administration of BC-819 and intravenously administered gemcitabine.
      Intratumoral injections of BC-819 will be performed using endoscopic ultrasound (EUS).

      Primary Objective: To assess the effect of intratumoral endoscopic ultrasound injection of
      BC-819 administered with intravenous gemcitabine on progression-free survival.

      Secondary Objectives: To compare the effects of intratumoral injection of BC-819 administered
      in combination with intravenous gemcitabine vs. intravenous gemcitabine alone on:

      Overall survival, Response rate, Resectability of the target tumor lesion, Quality of life,
      Safety, Serological Tumor Marker: CA 19-9, Duration of response, Failure-free survival
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males or females > 18 years of age

          2. If female, must not be pregnant or nursing; women of child-bearing potential must
             practice a medically approved method of contraception

          3. If male, must practice a medically approved method of contraception if have a partner
             of childbearing potential

          4. Histologically or cytologically confirmed adenocarcinoma of the exocrine pancreas

          5. Locally advanced pancreatic cancer (LAPC) that is clinically unresectable as defined
             in the NCCN Guidelines

          6. Karnofsky performance status (KPS) ≥ 70% at baseline

          7. Adequate hematological, renal, and hepatic function

               -  Platelet count ≥ 100,000/mm3

               -  Absolute neutrophil count (ANC) ≥ 1500/mm3

               -  Hemoglobin ≥ 10.0 g/dL (may be achieved by transfusion)

               -  Creatinine (≤ 1.5 x ULN)

               -  ALT, AST (≤ 1.5 x ULN)

               -  Total Bilirubin (≤ 1.5 x ULN)

          8. Have a target tumor lesion in the pancreas ≤ 6 cm in diameter that is accessible for
             intratumoral administration by EUS guidance as determined by the physician performing
             the EUS injection

          9. Have a biopsy specimen that is positive for H19 expression (grade 2 or greater
             staining determined by a pathologist). H19 expression can be determined based on a
             biopsy specimen collected before study participation, if available.

         10. No prior diagnosis of malignancy within 3 years except for curatively treated
             non-melanoma skin or in situ malignancies

         11. Able to comply with the protocol procedures

         12. Able and willing to provide written (signed) Informed Consent to participate in the
             study

        Exclusion Criteria:

          1. Have distant metastatic spread (such as liver or lung metastases), peritoneal spread
             or malignant ascites. Regional lymph node involvement may be considered in accordance
             with the PI's judgment

          2. Received any prior therapy for the treatment of pancreatic malignancy (including
             chemotherapy, immunotherapy, vaccines, monoclonal antibodies, major surgery, or
             irradiation, whether conventional or investigational, other than up to4 single doses
             of gemcitabine chemotherapy.Patients who received prior gemcitabine will only be
             eligible, if they enter the study without evidence of disease progression.

          3. Known human immunodeficiency virus (HIV) or hepatitis C virus (HCV) or hepatitis B
             virus (HBV) infection

          4. Have clinically significant pancreatitis within 12 weeks of treatment

          5. Have a clinical history of significant coagulopathy

          6. Have a medical condition contraindicated for endoscopic-guided delivery and/or for IV
             administration of Gemcitabine 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

          7. Have participated in any experimental therapeutic research study with an unapproved
             drug within 4 weeks of the screening visit

          8. Patients who require ongoing anticoagulation for pre-existing conditions, e.g.,
             thrombophlebitis, pulmonary embolus or atrial fibrillation