Phase II Study of PX-12 in Patients With Advanced Pancreatic Cancer

Inclusion Criteria:

- Histologically- or cytologically-confirmed diagnosis of advanced carcinoma of the pancreas (stage IV disease only).

- Patients whose tumor has progressed on gemcitabine or on a gemcitabine-containing combination. Patients must have received no more than two prior regimens for metastatic disease. Use of gemcitabine as a radiation sensitizer in combination with radiotherapy for localized disease will not be considered a prior gemcitabine-containing regimen if gemcitabine was received for ≤ 1 month following completion of radiotherapy. In addition, the use of 5-fluorouracil as a radiation sensitizer for localized disease will be allowed and not counted as a prior regimen if the 5-FU was continued for ≤ 1month following completion of radiotherapy.

- Karnofsky Performance Status of ≥ 70%.

- Patients must have discontinued previous anti-cancer therapy or other investigational agent at least three weeks or within 5 half lives of the drug (whichever is shorter) prior to entry into the study (six weeks for mitomycin C or nitrosureas) provided that all toxicities from prior treatment have resolved to a Grade 1 or less.

- Patients must have discontinued radiation therapy at least two weeks prior to entry into the study and have recovered from all radiation-related toxicities.

- Adequate organ function including the following:

- ANC ≥ 1500 cells/microL; platelets > 100,000/microL; hemoglobin ≥ 9 g/dL (may be transfused to this level).

- Bilirubin ≤ 2.0 mg/dL; aspartate transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) ≤ 3.0 times institutional upper limit of normal (ULN) OR < 5 times institutional ULN if the subject has documented liver metastases.

- Creatinine ≤2.0 mg/dL.

- CA19-9 level >2 times ULN.

- Disease that is measurable by CT scan per RECIST criteria (Appendix IV).

- PET/CT or PET scan with SUV of ≥ 5.0 in at least one lesion on an 18F FDG scan.

Exclusion Criteria:

- Active infection requiring antibiotics at study entry.

- Any serious concomitant systemic disorder that in the opinion of the investigator would place the patient at excessive or unacceptable risk of toxicity.

- Patients with active (requiring continuous medical therapy) pulmonary disease (COPD, asthma) or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest X-ray or PET/CT scan.

- Significant central nervous system or psychiatric disorder(s) that preclude the ability of the patient to provide informed consent.

- Known or suspected brain metastases that have not received adequate therapy. Patients must be stable without requirement for steroids or seizure medications.

- Major surgery within 4 weeks of study entry.

- Chemotherapy/investigational drugs within 3 weeks or within 5 half lives of the drug (whichever is shorter) of study entry, provided that all toxicities from prior treatment have resolved to a Grade 1 or less.

- Inability to tolerate prophylactic (1 mg/day) coumadin.