To pursue other indications

This study assesses the safety and efficacy of RTA 402 in combination with gemcitabine in patients with unresectable pancreatic cancer.

Phase I will be conducted to determine the MTD of RTA 402 (administered orally Days 1-21 or Days 1-28 of a 28-day cycle) in combination with gemcitabine (1000 m/m2). Gemcitabine will be administered as an intravenous infusion on Days 1, 8, and 15 of each 28-day cycle.

The phase II portion of the study will be randomized, and double-blinded. Phase II will utilize the RTA 402 MTD determined in Phase I; Arm 1 will consist of gemcitabine + RTA 402. RTA 402 capsules will administered orally Days 1-21 of each 28-day cycle (or Days 1-28 if appropriate, based on phase I results); gemcitabine (1000 mg/m2) will be administered as an intravenous infusion on Days 1, 8, and 15 of each 28-day cycle in each Arm. Arm 2 will consist of gemcitabine + placebo, placebo capsules will be taken orally Days 1-21 of each 28-day cycle (or Days 1-28 if appropriate, based on phase I results). Both treatment arms are 4-weeks in length.

The study was conceived with both a Phase I and Phase II portion as described above; however, only the Phase I portion was completed. The trial was terminated in 2009 before the Phase II portion could begin.

Inclusion Criteria:

• Phase I patients should have treatment naïve pancreatic cancer; however , Phase I patients who have had 1 prior regimen consisting of adjuvant chemo-radiation or adjuvant gemcitabine - as defined within the NCCN guidelines may be enrolled. Phase II patients must have metastatic disease (Stage IV only).
• Karnofsky performance status of >70%
• Adequate liver function. (total bilirubin ≤ 1.5 mg/dL and AST(SGOT) and ALT(SGPT) of < 2.5 ULN ( ≤ 5 ULN for Phase II patients with liver metastases), Serum Creatinine < 1.5 ULN
• Adequate bone marrow function as documented by the following laboratory test results within 14 days of starting therapy. platelets ≥100,000/mm3, absolute neutrophil count (ANC) ≥1500/mm3, hemoglobin ≥9.0 g/dL, white blood cell (WBC) count ≥3000 /mm3
• Practice effective contraception during the entire study period.
• Life expectancy of more than 3 months.
• Able and willing to sign the informed consent form.
• Willing and able to self-administer orally and document all doses of RTA 402 ingested.

Exclusion Criteria:

• Prior treatment for current malignancy outside of the adjuvant setting for Phase I
• Inability to swallow tablets or capsules
• Active brain metastases or primary central nervous system (CNS) malignancies. (Patients with a previously treated brain metastasis may be included.)
• Active second malignancy
• Ten percent or greater weight loss over the 6 weeks before study entry.
• Pregnant or breast feeding
• Clinically significant illnesses which could compromise participation in the study, including, but not limited to: Uncontrolled diabetes; Active or uncontrolled infection; Acute or chronic liver disease; Confirmed diagnosis of Human immunodeficiency virus (HIV) infection; Uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled cardiac arrhythmia.
• Psychiatric illness that would limit compliance with study requirements.

In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/