A Phase I/II Open-Label Dose-Escalation Clinical Trial of CPI-613 in Combination With Gemcitabine in Cancer Patients

Inclusion Criteria

• •For Stages 1 and 2 of the study, histologically documented unresectable primary or metastatic carcinoma of the pancreas, Stage II-IV, diagnosed within the past 8 weeks, intended to be treated with Gemcitabine as a single agent at 1000 mg/m\^2 once weekly for 3 weeks repeating the cycle every 4 weeks. For Stage 1 but not Stage 2 of the study, patients also include those with histologically documented unresectable primary or metastatic carcinoma other than pancreatic carcinoma (e.g., bladder cancer, NSCLC, and biliary tract cancer) who are intended to be treated with Gemcitabine as a single agent at 1000 mg/m\^2 once weekly for 3 weeks repeating the cycle every 4 weeks, regardless if Gemcitabine is used as second, third or fourth line treatment.
• •Eastern Cooperative Oncology Group (ECOG) performance status being 0-2.
• •Expected survival \>2 months.
• •18-70 years of age of both genders
• •Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device \[IUD\], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation.
• •Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists.
• •No radiotherapy, treatment with cytotoxic agents or chemotherapeutic agents (except CPI-613), or treatment with biologic agents within the 2 weeks prior to treatment with CPI-613. At least 2 weeks must have elapsed from any prior surgery or hormonal therapy. Patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment). Patients with persisting, stable chronic toxicities from prior treatment ≤Grade 1 are eligible, but must be documented as such.
• •Laboratory values ≤2 weeks must be:
• •* Adequate hematologic (white blood cell \[WBC\] ≥3500 cells/mm\^3 or ≥3.5 bil/L; platelet count ≥150,000 cells/mm\^3 or ≥150 bil/L; absolute neutrophil count \[ANC\] ≥1500 cells/mm3 or ≥1.5 bil/L; and hemoglobin ≥9 g/dL or ≥90 g/L).
• •* Adequate hepatic function (aspartate aminotransferase \[AST/SGOT\] ≤3x upper normal limit \[UNL\], alanine aminotransferase \[ALT/SGPT\] ≤3x UNL (≤5x UNL if liver metastases present), bilirubin ≤3x UNL).
• •* Adequate renal function (serum creatinine ≤2.0 mg/dL or 177 µmol/L).
• •* Adequate coagulation (International Normalized Ratio or INR must be≤1.5)
• •No evidence of active infection and no serious infection within the past month.
• •Mentally competent, ability to understand and willingness to sign the informed consent form.