Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Phase II/III, Study of TNFerade™ Biologic With 5-FU and Radiation Therapy for First-line Treatment of Unresectable Locally Advanced Pancreatic Cancer
Brief Summary: The primary purpose of this study is to assess the safety and effectiveness of TNFerade™ Biologic when administered concurrently with 5-FU and radiation therapy as first-line treatment of unresectable locally advanced pancreatic cancer.

TNFerade™ is a replication deficient adenovirus vector containing the gene for TNF-alpha controlled by a chemoradiation inducible promoter. This allows the expression of TNF-alpha to be greatest in the area receiving radiation. TNF-alpha is a cytokine that has been shown to have potent anti-cancer activities but, due to systemic toxicity, could not be delivered at effective doses. TNFerade™ Biologic is a novel way of selective delivery of TNF-alpha to tumor cells.

TNFerade™ Biologic will be injected during five weekly injection sessions, concomitant with radiation and 5-FU. TNFerade™ Biologic will be administered by direct intratumoral injection using a percutaneous approach (PTA) or endoscopic ultrasound (EUS).


Options:
A: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed adenocarcinoma of the pancreas

  * No other pancreatic tumor type, including either of the following:

    * Neuroendocrine tumor
    * Ampulla of Vater carcinoma
  * Metastatic disease
* Measurable or evaluable disease
* Unresectable disease, defined as either of the following:

  * Failed prior attempt of surgical resection by laparotomy
  * Surgical resection contraindicated by radiographic criteria (e.g., arterial vascular invasion)
* No cerebral metastases

PATIENT CHARACTERISTICS:

Age

* 18 to 75

Performance status

* Karnofsky 70-100%

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3

Hepatic

* Bilirubin \< 1.5 times upper limit of normal
* No hepatic disturbance

Renal

* Creatinine \< 120 mmol/L

Cardiovascular

* No untreated cardiac or coronary insufficiency
* No uncontrolled symptomatic arrhythmia
* No uncontrolled angina

Pulmonary

* No uncontrolled respiratory insufficiency

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No other malignancy except basal cell skin cancer or carcinoma in situ of the cervix
* No peripheral neuropathy ≥ grade 2
* No ongoing active infection
* No other serious uncontrolled medical disorder that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* No prior radiotherapy to the celiac or pancreatic area

Surgery

* See Disease Characteristics
B: Inclusion criteria:

* Histologically or cytologically proven pancreatic carcinoma
* Measurable locally advanced or metastatic disease
* Patient previously treated with 5-FU as a "radiation sensitizer" and all toxicities must have been resolved
* Patients must have received Gemcitabine-based chemotherapy (single agent or combination) as 1st line therapy for advanced or metastatic disease and all toxicities must have been resolved
* Patients received the last dose of gemcitabine at least 2 weeks prior to randomization
* Confirmed radiographic disease progression (Computed Tomogram (CT) scan or Magnetic Resonance Imaging (MRI) within 4 weeks prior to randomization
* Adequate liver and kidney function:

  * Total bilirubin inferior than 1.5 Upper Limit of Normal (ULN)
  * Creatinine clearance (ClCr) superior than 50 mL / min
  * Aspartate Transferase (AST) inferior than 3 ULN if no liver metastasis or AST inferior than 5 ULN if liver metastasis
  * Alanine Aminotransferase (ALT) inferior than 3 ULN if no liver metastasis or ALT inferior than 5 ULN if liver metastasis
* Adequate hematological function:

  * Neutrophils superior or egal to 1.5 x 109/L
  * Platelets superior or egal to 100 x 109/L

Exclusion criteria:

* Peripheral sensory or motor neuropathy \> grade 1
* Eastern Cooperative Oncology Group (ECOG) Performance status \> 2
* Serious cardiac arrhythmia, diabetes, or serious active infection or other active illness that would preclude study participation in the opinion of the investigator
* Pernicious anemia or other megaloblastic anemia with vitamin B12 deficiency
* Previous (greater than 5 years) or current malignancies of other origin within the past 5 years
* Lack of physical integrity of the upper gastrointestinal tract, clinically significant malabsorption syndrome, or inability to take oral medications
* History of known allergy to oxaliplatin or other platinum compounds, to 5-FU, to LV or to any ingredients in the formulations or the containers
* Severe renal impairment (ClCr \< 50 mL/min)
* Pregnant women or breast-feeding
* Patients (male or female) with reproductive potential not implementing accepted and effective method of contraception (the definition of "effective method of contraception" will be based on the investigators' judgment)

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
C: Inclusion Criteria

* Age ≥18 years old
* Patients with unresectable, locally advanced adenocarcinoma of the pancreas proven by biopsy or cytology (defined as direct extension to the SMA and/or celiac axis with absence of a fat plane between the low-density tumor and these arterial structures, or loss of patent superior mesenteric-portal vein confluence), who have not received previous treatment for pancreatic cancer. Patients who have been surgically explored and deemed unresectable on that basis are eligible, provided other entry criteria are met
* Informed consent
* Karnofsky performance status = or \>70%
* Life expectancy greater than 3 months
* Measurable disease

Exclusion Criteria

* Metastatic (stage IV) disease (including involvement of the colon, adrenals, or kidney, or radiographic evidence of peritoneal seeding)
* Patients with ascites detected by CT, US or MRI
* Patients with bulky celiac adenopathy (i.e., \> 2.5 cm)
* Diagnosis of islet cell tumor of the pancreas, lymphoma of the pancreas
* History of other malignancy in the past 2 years except carcinoma in situ of the cervix or bladder, non-melanomatous skin cancer or localized early stage prostate cancer
* Previous chemotherapy or radiation for pancreatic cancer or previous radiation to the target field
* Liver enzymes \>3 x ULN (ALT, AST, total bilirubin, alkaline phosphatase)
* Coagulopathy (INR \>1.5, PTT ratio \>1.5)
* Renal insufficiency (serum creatinine \>2.0 mg/dL)
* Significant anemia (e.g. hematocrit \<28% or hemoglobin \<9 g/dL) (may have RBC transfusion), or thrombocytopenia (platelet count \<100,000/µL); or neutropenia (ANC \<1500/µL)
* Patients with clinically significant pancreatitis within 12 weeks of treatment
* Pancreatic pseudocyst
* Contraindication to both percutaneous- and endoscopic- guided delivery
* Patients with history of deep venous thrombosis or pulmonary embolus
* Patients with doppler evidence of deep venous thrombosis at screening
* Patients with history of coagulopathy or known thrombophilic disorders
* Patients receiving hormone replacement therapy including oral contraceptives within 2 weeks prior to Day 1.
* Clinical evidence of active infection of any type, including hepatitis B or C virus
* Pregnant or lactating women. It is recommended that both men and women use condoms or another barrier method of birth control for at least 8 weeks following the last administration of TNFerade™ biologic and some form of birth control for at least 1 year
* Experimental medications within the last 4 weeks prior to Day 1
* Surgery within the last 4 weeks prior to Day 1 (if patient was ambulatory within 48 hours of surgery, patient may be considered eligible)
* Chronic systemic corticosteroid use at superphysiologic doses (greater than 10mg prednisone per day or equivalent)
* Significant concurrent medical or psychiatric illness which, in the opinion of the investigator, would interfere with the patient's ability to participate in the trial

Please note that there are additional entry criteria. The study center will determine if you meet all criteria. If you do qualify to participate, study personnel will explain the study and answer any questions you may have. You can decide whether or not you wish to participate but if you do not qualify for this trial, study staff will explain the reasons. Please contact your local center listed below, or call the toll free PACT study line for assistance at 1-888-344-6096
D: Inclusion Criteria:

* Age between 18 and 75 years
* Histologically proven pancreatic cancer stage III or IV (T1-3 N1M0 or T1 3N0 1M1)
* No option for resection with curative intent
* At least one measurable or not measurable lesion (according to RECIST)
* No previous chemotherapy or other systemic tumor therapy
* No previous radiation
* Performance-Status 0-2 according to WHO/ECOG
* Life expectancy of at least 3 months
* Adequate kidney-, liver- and bone marrow function, defined as
* Absolute neutrophil count \* 1,5 x 109/l
* Hemoglobin \* 8 g/dl
* Thrombocytes \* 100 x 109/l
* Bilirubin \* 2 x upper norm (with liver mets \< 5-fold)
* Serum Creatinine \* 1,25 x upper norm
* Creatinine clearance \> 30 ml/min (Cockroft/Gault)
* Transaminases \* 2,5 x upper norm (with liver mets \< 5-fold)
* Possibility of regular long-term follow-up
* Negative pregnancy test in women at childbearing age
* All patients must have signed an informed consent before study entry.

Exclusion Criteria:

* Known secondary cancer other than curatively treated basalioma or carcinoma in situ of the cervix uteri
* Clinically unstable CNS-metastases
* Known hypersensitivity against study medication
* Severe impairment of renal function (creatinine clearance \< 30 ml/min)
* Severe impairment of liver function (bilirubin \> 2,0 x above upper norm, transaminases \> 2,5 x upper norm, or with known liver metastasis \>5 x upper norm)
* Clinically relevant disease of the cardiovascular system or other vital organs
* Known polyneuropathy
* Known DPD-deficiency (screening not required)
* Simultaneous treatment with the antiviral agent sorivudin or chemically related agents such as brivudin
* Pregnancy, lactation or lack of reliable contraception in women at childbearing age
* Mental disease, drug- or alcohol abuse
* Participation in another clinical trial within the last 4 weeks
* All other diseases which may prevent adequate participation in the trial
* Indication of lack of compliance with study regulations

Answer: C