• To compare the overall survival durations of the two treatment arms. [ Time Frame: one year ] [ Designated as safety issue: No ]
• To evaluate and compare the tolerability and toxicity of the two treatment arms. [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]

• To compare the objective response rates of the two treatment arms. [ Time Frame: one year ] [ Designated as safety issue: No ]
• To compare the progression free survival (PFS) of the two treatment arms. [ Time Frame: one year ] [ Designated as safety issue: No ]
• To evaluate the 1-year survival rates of the two treatment arms. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
• To evaluate the changes in blood levels of CA19.9 on the two treatment arms and whether there is a relationship to objective response, and PFS. [ Time Frame: one year ] [ Designated as safety issue: No ]
• To evaluate the OS, ORR, PFS, 1-year survival, and changes in CA19.9 of subjects on the two treatment arms that completed > 1 cycle (28 days) of protocol treatment. [ Time Frame: one year ] [ Designated as safety issue: No ]

The purpose of this study is to determine if imexon in combination with gemcitabine could improve overall survival as compared to gemcitabine alone in subjects with pancreatic cancer that has spread to other organs such as the liver or lungs. The study will also look at the safety of the combination as compared to gemcitabine alone. Participants in the study will be randomly assigned to either treatment and neither the participant or their doctors will know which treatment they will be receiving.

• Drug: imexon + gemcitabine
• Drug: imexon placebo + gemcitabine

• Experimental: Amplimexon + gemcitabine
• Active Comparator: Amplimexon placebo + gemcitabine

Inclusion Criteria:

1. Patients with histologically or cytologically confirmed, chemotherapy naive, metastatic pancreatic adenocarcinoma (Stage IV). This does not include patients with only locally advanced pancreatic cancer.
2. At least one unidimensional measurable metastatic lesion by contrast enhanced CT scan (or MRI in patients ineligible for contrast enhanced CT) that are outside any prior radiation port (Appendix C, Sections 6.3 and 6.4).
3. Age at least 18 years.
4. ECOG performance status 0 or 1 (Appendix D).
5. No prior chemotherapy or radiation therapy.
6. Projected life expectancy at least 2 months.
7. If female, neither pregnant nor lactating.
8. If of child bearing potential must agree to, and be able to use adequate contraception.
9. Concomitant disease: No respiratory insufficiency requiring oxygen therapy; no angina at rest; no myocardial infarction in previous 3 months; no life threatening ventricular arrhythmias. No uncompensated CHF or NY Heart Association class 3 or 4 cardiac disease (Appendix D).
10. No other concurrent active malignancy.
11. No infection requiring parenteral antibiotic therapy at the start of protocol treatment.

12. Laboratory values within the following criteria:

    Hgb greater than or equal to 9 gm/dL WBC greater than or equal 3,500/mm3 ANC greater than or equal 1,500/mm3 Platelet count greater than or equal 100,000/mm3 Creatinine greater than or equal 2.0 Bilirubin less than or equal to 2.0 Hepatic enzymes (AST, ALT) less than or equal 3 times upper limit of normal (ULN)

13. G6PD level greater than or equal lower limit of normal (LLN).
14. Able to render informed consent and follow protocol requirements.

Exclusion Criteria:

1. Patients with locally advanced, non-metastatic pancreas cancer (Stage III or below).
2. Age less than 18 years.
3. ECOG performance status 2 or greater.
4. Prior anticancer drug therapy for metastatic disease.
5. Ascites.
6. Prior abdominal or thoracic surgery < 4 weeks before the start of therapy.
7. Current or prior brain metastases. Brain MRI or CT required pre-registration only if the patient has CNS symptoms indicating a need for evaluation.
8. Life expectancy projected less than 2 months.
9. Pregnancy or lactation.
10. Unable or unwilling to utilize medically acceptable contraception if of childbearing potential.
11. Laboratory parameters outside of specified ranges, (see above).
12. Infection requiring parenteral antibiotics.
13. NY Heart Association stage 3 or 4 heart disease.
14. Unable to render informed consent.
15. Failure to meet any of the eligibility criteria as outlined above.