Talimogene Laherparepvec in Patients With Unresectable Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Talimogene Laherparepvec
Intervention description: Talimogene laherparepvec administered by direct injection into pancreatic tumors using EUS-guided FNI, up to a maximum of 4 mL per treatment.
Intervention MeSH terms: Talimogene laherparepvec
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic; Pancreas; Adenocarcinoma

Summary:

      The purpose of the study is to assess the safety of injections of talimogene laherparepvec
      into patients with pancreatic cancer that cannot be removed by surgery. The study will also
      test whether the injections are effective in treating the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  cytological or histological proof of adenocarcinoma of the pancreas

          -  unresectable, locally advanced disease (isolated liver metastases are permitted)

          -  tumors of at least 1 cm diameter at screening

          -  measurable disease using Response Evaluation Criteria In Solid Tumors (RECIST)
             criteria

          -  failure of either standard therapy, OR any one of the following:

               -  no alternative therapeutic of higher curative potential is available;

               -  investigator determination that patient could not tolerate alternative
                  therapeutic due to unacceptable toxicity; or,

               -  patient refusal to be treated with available alternative therapeutic

          -  age > 18 years

          -  life expectancy > 3 months

          -  adequate bone marrow function as indicated by:

               -  White blood cells (WBC) ≥ 3.0 x 10^9/L

               -  platelets ≥ 100 x 10^9/L

               -  hemoglobin ≥ 8.5 gm/dL

          -  adequate liver function as indicated by:

               -  bilirubin < 1.5 x upper limit of normal (ULN)

               -  alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5 x ULN in
                  case of presence of liver metastasis

               -  ALT or AST < 2.5 x ULN in case of absence of liver metastasis

          -  adequate renal function as indicated by a serum creatinine level < 1.5 x ULN.

          -  adequate hemostasis indicated by international normalized ratio (INR) ≤ 1.5

          -  mentally, physically and geographically able to undergo treatment and follow-up

          -  provided written informed consent

          -  first patient in each cohort only: seropositive for herpes simplex virus type 1 (HSV1)

        Exclusion Criteria:

          -  history of other malignancy within two years prior to screening, except for prostate
             cancer (T1c, T2ab with definitive treatment, prostate-specific antigen (PSA) < 1
             ng/ml, and without ongoing hormone suppression) or adequately treated in situ
             carcinoma of the cervix, basal cell carcinoma, or squamous cell carcinoma of the skin

          -  cystic form of pancreatic cancer; microcystic disease may be eligible upon discussion
             with Medical Monitor

          -  Common Terminology Criteria for Adverse Events (CTCAE) version 3 grade 2 or greater
             clinical pancreatitis within 8 weeks prior to dosing with OncoVEX^GM-CSF

          -  other than metastases limited to the liver, imaging evidence of metastatic disease to
             any other organ or tissue

          -  any serious concomitant systemic disorder that would compromise the safety of the
             patient, at the discretion of the investigator

          -  evidence of compromised immune function including but not limited to:

               -  clinically significant absolute lymphocyte count < Lower Limit of Normal (LLN)

               -  known human immunodeficiency virus (HIV), acute or chronic active hepatitis B, or
                  hepatitis C infection;

               -  concurrently taking HIV antiviral medications (e.g. protease inhibitors,
                  azidothymidine, etc.)

          -  received intravenous (IV), intramuscular (IM) or subcutaneous (SC) human gamma
             globulin within 6 months prior to dosing with OncoVEX^GM-CSF

          -  patients taking immunosuppressive agents (e.g. cyclosporine, tacrolimus, or oral or
             systemic corticosteroids at a dose of > 10 mg/day of prednisone or equivalent).

          -  pregnancy, lactation or lack of effective contraception in women of child-bearing
             potential (e.g., not post menopausal for > 2 years, or had tubal ligation); lack of
             effective contraception in men if the partner is of child-bearing potential; women
             must have been practicing an effective contraceptive method for at least three months
             prior to entry in to the trial (hormonal contraception or intrauterine device in
             conjunction with a barrier method); men must use a condom or be surgically sterilized

          -  patients with active bacterial or viral infections that require treatment with
             systemic antibiotics or antiviral agents within 2 weeks prior to the first dose of
             OncoVEX^GM-CSF); (note: patients with active cold sores or other HSV1 infections must
             wait until those lesions have crusted over before receiving OncoVEX^GM-CSF)

          -  surgery requiring general or spinal anesthesia within four weeks prior to dosing with
             OncoVEX^GM-CSF

          -  Treatment with an investigational agent within 4 weeks prior to the first dose of
             OncoVEX^GM-CSF

          -  serum carbohydrate antigen (CA)19.9 levels > 3000 U/mL at screening

          -  evidence of ascites on screening abdominal computed tomography (CT) scan