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.

Exclusion Criteria:

- Prior therapy with Gemcitabine

- Serious medical illness, such as significant cardiac disease (e.g. symptomatic
congestive heart failure, unstable angina pectoris, myocardial infarction within the
past 6 months, uncontrolled cardiac arrhythmia, or New York Heart Association Class
III or IV), or severe debilitating pulmonary disease, that would potentially increase
patients' risk for toxicity.

- Patients with active central nervous system (CNS) or epidural tumor.

- Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g.,
active peptic ulcer disease).

- Pregnant women, or women of child-bearing potential not using reliable means of
contraception (because the teratogenic potential of CPI-613 is unknown).

- Lactating females.

- Fertile men unwilling to practice contraceptive methods during the study period.

- Life expectancy less than 2 months.

- Any condition or abnormality which may, in the opinion of the investigator,
compromise the safety of patients.

- Unwilling or unable to follow protocol requirements.

- Dyspnea with minimal to moderate exertion. Patients with large pleural, pericardial,
or peritoneal effusions.

- Active heart disease including myocardial infarction within previous 6 months,
symptomatic coronary artery disease, arrhythmias requiring medication, or symptomatic
congestive heart failure.

- Albumin <2.5 g/dL or <25 g/L.

- Evidence of active infection, or serious infection within the past month.

- Patients with known HIV infection.

- Patients receiving any other standard or investigational treatment for their cancer,
or any other investigational agent for any indication within the past 4 weeks prior
to initiation of CPI-613 treatment.

- Patients who have received immunotherapy of any type within the past 4 weeks prior to
initiation of CPI-613 treatment.

- Requirement for immediate palliative treatment of any kind including surgery.

- Patients that have received a chemotherapy regimen with stem cell support in the
previous 6 months.

- A marked baseline prolongation of QT/QTc interval (e.g., repeated exhibition of a QTc
interval >470 ms.)

- A history of additional risk factors for torsade de pointes (e.g., heart failure,
hypokalemia, family history of Long QT Syndrome)

- Prior illicit drug addiction.

- Any condition or abnormality which may, in the opinion of the investigator,
compromise the safety of the patient.