Gemcitabine Hydrochloride and Cisplatin With or Without Radiation Therapy in Treating Patients With Localized Liver Cancer That Cannot Be Removed by Surgery

PRIMARY OBJECTIVES:

I. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect
to overall survival (OS) for patients with unresectable, localized intrahepatic
cholangiocarcinoma.

SECONDARY OBJECTIVES:

I. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect
to local control for patients with unresectable, localized intrahepatic cholangiocarcinoma.

II. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect
to adverse events for patients with unresectable, localized intrahepatic cholangiocarcinoma.

III. To evaluate the addition of liver-directed radiation therapy to chemotherapy with
respect to regional control for patients with unresectable, localized intrahepatic
cholangiocarcinoma.

IV. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect
to distant metastases for patients with unresectable, localized intrahepatic
cholangiocarcinoma.

V. To evaluate the addition of liver-directed radiation therapy to chemotherapy with respect
to progression-free survival for patients with unresectable, localized intrahepatic
cholangiocarcinoma.

After completion of study treatment, patients are followed up every 3 months for 3 years then
every 6 months for 5 years.

Inclusion Criteria:

- Pathologically (histologically or cytologically) proven diagnosis of intrahepatic
cholangiocarcinoma (IHC) without distant extrahepatic metastasis within 90 days of
registration; patients with an adenocarcinoma suggestive of a pancreaticobiliary
primary with radiographic findings consistent with an intrahepatic cholangio-carcinoma
are eligible

- Patient must have 1 lesion with a maximum AXIAL diameter of 12 cm; up to 3 satellite
lesions are permitted; satellite lesions, are defined as lesions less than 2 cm that
are within 1 cm of the periphery of the dominant lesion (GTV) are permitted; the
satellite lesions are NOT included in the AXIAL diameter measurement; regional lymph
node involvement within the porta hepatis (as medial as superior mesenteric vein [SMV]
portal vein confluence) is permitted if nodes are deemed clinically positive (i.e.
fludeoxyglucose F 18 [FDG] avid)

- Appropriate stage for protocol entry, including no distant metastases, based upon the
following minimum diagnostic workup:

- History/physical examination within 30 days prior to registration

- Assessment by medical oncologist who specializes in treatment of IHC within 30
days of registration

- Pre-randomization scan (REQUIRED for all patients): computed tomography (CT) scan
chest/abdomen/pelvis with multiphasic liver CT scan within 30 days prior to
registration; if CT contrast is contraindicated, CT chest without contrast and
magnetic resonance imaging (MRI) of abdomen and pelvis is permitted

- Zubrod performance status 0-1 within 30 days prior to registration

- Absolute neutrophil count (ANC) >= 1,500 cells/m^3

- Platelets >= 100,000 cells/mm^3

- Total bilirubin < 2.5 mg/dl

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 5.0 X
institutional upper limit of normal

- Albumin >= 2.5 mg/dl

- Creatinine within normal institutional limits or creatinine clearance >= 60mL/min/1.73
m^2 for subject with creatinine levels above institutional normal

- Hemoglobin >= 9.0 g/dl; (note: the use of transfusion or other intervention to achieve
hemoglobin [Hgb] >= 9.0 g/dl is acceptable)

- Patient must provide study specific informed consent prior to study entry

- Negative beta human chorionic gonadotropin (bHCG) within 14 days prior to study entry
if patient is pre or perimenopausal

Exclusion Criteria:

- Multiple lesions that don't meet the criteria as satellite lesions

- Extrahepatic metastases or malignant nodes beyond the periportal region; celiac,
pancreaticoduodenal and para-aortic nodes > 2 cm are ineligible; note that benign
non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis
and is permitted, even if the sum of enlarged nodes is > 2.0 cm

- Maximum diameter exceeding 12 cm (maximum diameter does not include satellite lesion)

- Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal
bleed within 60 days prior to study entry

- Prior radiotherapy to the region of the liver that would result in overlap of
radiation therapy fields

- Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time

- Direct tumor extension into the stomach, duodenum, small bowel or large bowel

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 3 years; (note: carcinoma in situ of the breast, oral cavity, or
cervix is all permissible)

- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable

- Currently receiving other anti-cancer agents

- Participants who require anticoagulation should receive low-molecular weight or
standard heparin and not warfarin

- Prior surgery for the IHC; (liver resection is not allowed)

- Prior allergic reactions attributed to compounds of similar chemical or biologic
composition to gemcitabine (gemcitabine hydrochloride) or cisplatin

- Severe, active co-morbidity, defined as follows:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months

- Transmural myocardial infarction within the last 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days before
registration

- Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4
count < 200 cells/microliter; note that patients who are HIV positive are
eligible, provided they are under treatment with highly active antiretroviral
therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior
to registration; note also that HIV testing is not required for eligibility for
this protocol

- End-stage renal disease (i.e., on dialysis or dialysis has been recommended)

- Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception

- Grade 3 or higher peripheral neuropathy