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Irinotecan

Gemcitabine

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Irinotecan at 120 mg/m2 intravenously every three weeks + Capecitabine at 1500 mg/m2/day orally twice per day for a total of 14 days.

The treatment cycle is once every 21 days.

Irinotecan will be administered at infusion room over 60 minutes. Capecitabine will be administered by the patients at home. Unless there is early progression of disease, at least two courses will be administered to each patient. Repeated courses may be given to the patients who benefit from the treatment (either complete or partial remission, or stabilization of disease)

Irinotecan & Capecitabine

Fa-Chyi Lee, MD

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.

Irinotecan and Capecitabine as Second-line Treatment for Advanced/Metastatic Biliary Tract Cancers

A Phase II Trial of Combination Irinotecan and Capecitabine as Second-Line Treatment for Patients With Locally Advanced/Metastatic Biliary Tract Cancers Who Progressed or Intolerant to Front-Line Gemcitabine and Platinum Combination

The time from initiation of treatment to disease progression or death by any cause. Progression is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1). Progressive disease (PD) for target lesions: \>= 20% increase in the sum of diameters of the target lesions taking as reference the smallest sum on study, and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered . PD for non-target lesions is defined as unequivocal appearance of one or more new malignant lesions or unequivocal progression of existing non-target lesions.The Kaplan-Meier method will be used to calculate the proportion of subjects who are progression-free at 6 months along with its 95% confidence interval. Subjects lost to follow-up or who withdraw from the study for any reason will be censored at their last date of contact

Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1). Complete response (CR): Disappearance of all evidence of target and non-target lesions. Partial response (PR): \>= 30% reduction from baseline in the sum of the longest diameter of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Best overall response is the best response recorded from the start of treatment until disease progression/recurrence. (For definition of progression, see Outcome Measure 1). Overall response rate will be reported as the sum of the percentages of patients achieving CR and PR.

The time from study enrollment to death by any cause. Subjects who withdraw from the study for any reason or are lost to follow-up will be censored at their last date of contact. The Kaplan-Meier method will be used to calculate the median OS and 95% confidence interval

Toxicities will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE), ver. 4.0. Adverse events of grade 3 or higher will be reported as percentages of patients affected. If subjects experience the same toxicity more than once, the subjects' highest grade toxicity will be used for summaries.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Irinotecan and Capecitabine as Second-line Treatment for Advanced/Metastatic Biliary Tract Cancers	NCT02720601	Biliary Tract C...	Irinotecan & Ca...	18 Years -	New Mexico Cancer Care Alliance
Irinotecan and Capecitabine as Second-line Treatment for Advanced/Metastatic Biliary Tract Cancers	NCT02720601	Biliary Tract C...	Irinotecan & Ca...	18 Years -	New Mexico Cancer Care Alliance
Irinotecan and Capecitabine as Second-line Treatment for Advanced/Metastatic Biliary Tract Cancers	NCT02720601	Biliary Tract C...	Irinotecan & Ca...	18 Years -	New Mexico Cancer Care Alliance

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