CPI-613 in Treating Patients With Advanced or Metastatic Bile Duct Cancer That Cannot Be Removed By Surgery

PRIMARY OBJECTIVES:

I. To evaluate the safety and efficacy of CPI-613 (6,8-bis[benzylthio]octanoic acid) in
patients with advanced unresectable cholangiocarcinoma who have failed available therapies.

OUTLINE:

Pre-cycle: Patients receive 6,8-bis(benzylthio)octanoic acid intravenously (IV) over 2 hours
on days 1-5, 1 week prior to course 1.

Patients receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1 and 4 of weeks
1-3. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease
progression or unacceptable toxicity. Patients responding to treatment may receive up to 4
more courses of treatment.

After completion of study treatment, patients are followed up bimonthly.

Inclusion Criteria:

- Histologically and cytologically proven cholangiocarcinoma of any type (including
intrahepatic cholangiocarcinoma, extrahepatic primary cholangiocarcinoma, hilar
cholangiocarcinomas, cholangiocarcinomas located in the gall bladder or hepatic
capsule effraction, and carcinoma of the Ampulla of Vater, etc.) that is not amenable
to surgery, radiation, or combined modality therapy with curative intent, and has
failed or is not eligible for available chemotherapies such as gemcitabine with or
without platinum

- Local, locally-advanced, or metastatic disease documented as having shown progression
on a scan (e.g., computed tomography [CT], magnetic resonance imaging [MRI])

- Measurable tumor according to Response Evaluation Criteria in Solid Tumors (RECIST)
1.1 criteria with at least one unidimensionally measurable target lesion

- No evidence of biliary duct obstruction, unless obstruction is controlled by local
treatment or, in whom the biliary tree can be decompressed by endoscopic or
percutaneous stenting with subsequent reduction in bilirubin to below 1.5 x upper
level of normal (ULN)

- No acute toxic effects from previous treatment superior to grade 1 at the start of the
study

- Eastern Cooperative Oncology Group (ECOG) performance status being 0-3

- Expected survival > 3 months

- 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

- Granulocyte count >= 1500/mm^3

- White blood cell (WBC) >= 3500 cells/mm^3 or >= 3.5 bil/L

- Platelet count >=100,000 cells/mm^3 or >=100 bil/L

- Absolute neutrophil count (ANC) >=1500 cells/mm^3 or >=1.5 bil/L

- Hemoglobin >= 9 g/dL or >= 90 g/L

- Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x
upper normal limit (UNL), alanine aminotransferase (ALT/serum glutamate pyruvate
transaminase [SGPT]) =< 3 x UNL (=< 5 x UNL if liver metastases present)

- Bilirubin =< 1.5 x UNL

- Serum creatinine =< 2.0 mg/dL or 177 µmol/L

- 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:

- Patients receiving any other standard or investigational treatment for their cancer,
or any other investigational agent for any indication within the past 2 weeks prior to
initiation of CPI-613 treatment

- Serious medical illness that would potentially increase patients' risk for toxicity

- 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 3 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 moderate exertion; patients with clinically significant pleural or
pericardial effusions

- Active heart disease including but not limited to symptomatic congestive heart
failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic
myocardial infarction, or symptomatic congestive heart failure; also patients with a
history of myocardial infarction that is < 1 year prior to registration, or patients
with previous congestive heart failure (< 1 year prior to registration) requiring
pharmacologic support or with left ventricular ejection fraction < 50%)

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

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

- Patients with known human immunodeficiency virus (HIV) infection

- Patients who have received cancer immunotherapy of any type within the past 2 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

- Prior illicit drug addiction

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