Study was never submitted to the IRB & never opened. PI is leaving institution.

Biliary tract cancers that progress after first line treatment can be difficult to treat. There is a great need for an effective, tolerable, easy to administer second-line regimen. Previous early phase studies demonstrated that the combination of two chemotherapy drugs, irinotecan and capecitabine had activity in this setting. The goal of this study is to determine whether this drug combination, as a second-line treatment, can improve progression free survival in patients with biliary tract cancers.

The current front-line treatment regimen using gemcitabine in combination with cisplatin has a significant survival benefit (11.7 versus 8.1 months, P < 0.001) in patients with biliary tract cancer when compare to single agent gemcitabine. However, there is urgent need for effective second-line regimens with minimal toxicity.

Capecitabine (Xeloda) is an oral pro-drug of 5-fluorouracil (5-FU). The conversion to active drug is dependent on thymidine phosphorylase, which is expressed at a higher level in tumor cells than in normal tissue. There are no reports on prospective clinical trials using capecitabine in cholangiocarcinoma. However, case reports of successful stabilization of disease with single agent capecitabine are available. Since 5-FU has been the main chemotherapy agent for biliary tract cancer for more than 40 years, it is reasonable to presume that the overall effectiveness of capecitabine will be very similar to infusional 5-FU.

Several clinical trials have shown that irinotecan can be a good agent for cholangiocarcinoma. Of the five patients that had a partial response in one phase I trial of the combination of irinotecan and docetaxel in advanced solid tumors, one had cholangiocarcinoma. Two of the 11 patients that had a partial response from another phase I trial using a combination of irinotecan, oxaliplatin and 5-FU in advanced tumors had cholangiocarcinoma. A case report indicated that single agent irinotecan given at a low weekly dose could produce a long-lasting response in metastatic cholangiocarcinoma.

Based on the above data, our experience, and other early phase studies of this combination, this phase II trial was proposed to determine the progression free survival, response rate, overall survival, and toxicity in biliary tract cancer patients who are administered irinotecan and capecitabine as a second-line treatment.

Inclusion Criteria:

• Must be 18 years of age or older
• Histological proven un-resectable or metastatic biliary tract cancer (gallbladder cancer included) with radiologic progression after initial gemcitabine plus platinum (cisplatin, carboplatin or oxaliplatin) regimen
• Computerized tomography (CT) or magnetic resonance imaging (MRI) with measurable lesions no more than 28 days prior to enrollment. Lesions should be at least 1.5 cm in longest dimension.
• Patients with evaluable only disease, effusion, needs to have cytology proven malignant cells present in the effusion.
• Patients who cannot tolerate or developed allergic reaction to either gemcitabine or platinum compounds, even without radiographic progression will be eligible.
• Patients must have a life expectancy of at least 12 weeks
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
• Patients must be able to understand and sign informed consent.
• Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of ≥ 1,500 cells/mm3 and platelet count ≥ 60,000/mm3 and absence of a regular red blood cell transfusion requirement.
• Patients should have adequate hepatic function with a total bilirubin ≤ 4.0 mg/dl, could be ≤ 10 mg/dl if a functional biliary drain is placed within three days of enrollment and documented declining total bilirubin level, and adequate renal function as defined by a serum creatinine ≤ 1.5 X upper limit of normal.
• Patients with concurrent basal cell carcinoma and/or squamous cell carcinoma of skin are eligible.
• Patients with other malignancies require having at least 5 year disease-free interval before enrollment
• Patients who were treated with either irinotecan and/or capecitabine for cancers other than biliary tract cancer are eligible as long as treatment-free interval is greater than 3 years.

Exclusion Criteria:

• Patients with symptomatic central nervous system (CNS) metastases are excluded. Need to demonstrate stable CNS metastases for at least 3 months
• Pregnant women and nursing mothers are not eligible.
• Patients of child bearing potential must agree to use adequate contraception
• No heart attack within 6 months of enrollment
• No stroke (embolic and hemorrhage) within 6 months of enrollment.
• No New York Heart Association Class III/IV congestive heart failure (CHF).
• Severe chronic obstructive pulmonary disease (COPD) requires ≥ 2 L (Liters) /minute of oxygen.
• Known history of allergic reaction to irinotecan and/or capecitabine.
• Known history of 5-fluorouracil (5-FU) or capecitabine induced cardiac toxicity.