A Phase I Study of Adjuvant Chemotherapy With GC in Biliary Tract Cancer Undergoing Resection Without Major Hepatectomy

Study Overview
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Brief Summary
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To decide maximum tolerated dose and recommended dose of treatment using gemcitabine plus cisplatin combination therapy in patients with biliary tract cancer undergoing resection without major hepatectomy.

Detailed Description
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Surgery currently remains the only potentially curative treatment for biliary tract cancer (BTC), and most patients develop recurrence. Therefore, effective adjuvant chemotherapy is required to increase the curability of surgery and to prolong the survival in these patients. However, to date, no standard adjuvant chemotherapy has been established, and a guideline for BTC treatment recommends that trials of adjuvant chemotherapy be carried out. Based on results from clinical studies in unresectable BTC, gemcitabine, platinum agent, fluoropyrimidine are considered to have activity against BTC. These agents are expected to be effective in the postoperative adjuvant therapy for BTC, Thus, randomized controlled trials with gemcitabine are ongoing, and the results are expected. Recently, in the ABC-02 study, the first prospective multicenter phase III study in patients with unresectable BTC, gemcitabine/cisplatin combination chemotherapy was compared with gemcitabine monotherapy and showed that the combination therapy significantly prolonged MST (from 8.1 to 11.7 months; P < 0.001). Gemcitabine/cisplatin combination therapy is now considered to be the standard regimen for unresectable BTC, and we expect this regimen to be effective for postoperative adjuvant therapy. Though hepatectomy is frequently performed in surgery for BTC, it is unclear that the effect of anticancer agent is affected by hepatectomy. Because gemcitabine is metabolized by cytidine deaminase primarily in the liver, it considered to have decreased the metabolic ability of gemcitabine after hepatectomy. Some clinical studies demonstrated that patient with hepatectomy could not tolerate the standard dose and schedule of gemcitabine. In the adjuvant chemotherapy with gemcitabine, it is necessary to examine separately whether hepatectomy was undergone or not. In this study, we aimed to assess the safety and efficacy of gemcitabine/cisplatin combination chemotherapy in patients with biliary tract cancer undergoing curative resection without hepatectomy.

Official Title
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A Phase I Study of Adjuvant Chemotherapy With Gemcitabine Plus Cisplatin in Patients With Biliary Tract Cancer Undergoing Curative Resection Without Major Hepatectomy

Conditions
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Biliary Tract Cancer

Intervention / Treatment
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* Drug: gemcitabine , cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biliary tract cancer (BTC) with more than stage IB BTC undergoing R0 or R1 resection without major hepatectomy Older than 20 years old PS0 or 1 No treatment other than surgery No dysfunction of main organs Possible oral intake Treatment start; after 4 weeks and within 12 weeks after surgery Obtained written informed consent Exclusion Criteria: Patients with resection of major hepatectomy Patients with double cancers Patients having severe allergy Patients with severe organ dysfunction Patients with active infectious disease Pregnancy Patients with severe psychological disease Patients seem inadequate for this study by investigators

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: gemcitabine , cisplatin<br> | Drug: gemcitabine , cisplatin<br>* Dose of gemcitabine and cisplatin and treatment schedule<br>* Other names: Gemcitabine;gemzer,Cisplatin;Cispulan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose | To establish the maximum tolerated dose of gemcitabine plus cisplatin in patients with biliary tract cancer undergoing curative resection without major hepatectomy | Within 2 courses (every 2 weeks in Level -2 and -1; every 3 weeks in Level 0 and 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with dose limiting toxicity | Dose limiting toxicity is defined as follows Grade 4 neutropenia, thrombocytopenia Grade 3 or 4 febrile neutropenia Grade 3 or 4 non-hematological adverse events unless unresponsive to treatment Any adverse events resulting in interruption of dosing on day 8 in both the two courses Any adverse events resulting in dose modification or delay of longer than 2 week | At the end of adjuvant chemotherapy (6 months) |