A Phase 1-2, Multicenter, Open-Label Study of The X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 Given in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer

Inclusion Criteria:

- Patients with histologically or cytologically confirmed advanced pancreatic
adenocarcinoma who are candidates for first-line gemcitabine therapy

- Karnofsky performance >70%

- One or more metastatic tumors measurable by RECIST criteria on CT scan or MRI (Phase
2 part only)

- Life expectancy of at least 3 months

- Age > 18 years

- Signed, written IRB-approved informed consent

- A negative serum pregnancy test (if applicable)

- Acceptable liver function:

- Bilirubin < 1.5 times the institution's upper limit of normal

- AST (SGOT), ALT (SGPT) and Alkaline phosphatase < 2.5 times the institution's upper
limit of normal

- Acceptable renal function:

- Serum creatinine within normal limits, OR calculated creatinine clearance > 60
mL/min/1.73 m2 for patients with creatinine levels above institutional normal

- Acceptable hematologic status:

- Granulocyte > 1500 cells/uL

- Platelet count > 100,000 plt/uL

- Hemoglobin > 9.0 g/dL

- Acceptable coagulation status:

- PT within normal limits

- PTT within normal limits

- For women of child-producing potential, the use of effective contraceptive methods
during the study

- Prior radiotherapy for local disease is allowed provided disease progression has been
documented, and treatment completed at least 4 weeks prior to registration

Exclusion Criteria:

- Prior chemotherapy for pancreatic cancer, except for 5-fluorouracil or gemcitabine
given as a radiosensitizer

- Active progressive brain metastases including the presence of any related symptoms or
need for corticosteroids. A CT or MRI scan of the head is necessary in patients with
a history of brain metastases to document the stability of prior lesions.

- Known bleeding diathesis or concurrent treatment with anticoagulants except patients
on non-therapeutic line maintenance coumadin

- Pregnant or nursing women. NOTE: Women of child-bearing potential must agree to use
adequate contraception (sterile or surgically sterile; hormonal or barrier method of
birth control; or abstinence) prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately

- Men who are unwilling to use acceptable forms of birth control when engaging in
sexual contact with women of child bearing potential

- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy

- Known infection with HIV, hepatitis B, or hepatitis C

- Serious nonmalignant disease that could compromise protocol objectives in the opinion
of the investigator and/or the sponsor

- Patients who are currently receiving any other investigational agent. Subjects who
have used a previous antisense oligonucleotide in the last 90 days will be excluded

- Unwillingness or inability to comply with procedures required in this protocol