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

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

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.

Study Overview

• Status: Completed
• Conditions: Biliary Tract Cancer
• Intervention / Treatment: Drug: gemcitabine , cisplatin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kobe, Japan, 650-0017
    • Kobe University Graduate School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Biliary tract cancer (BTC) with more than stage IB
2. BTC undergoing R0 or R1 resection without major hepatectomy
3. Older than 20 years old
4. PS0 or 1
5. No treatment other than surgery
6. No dysfunction of main organs
7. Possible oral intake
8. Treatment start; after 4 weeks and within 12 weeks after surgery
9. Obtained written informed consent

Exclusion Criteria:

1. Patients with resection of major hepatectomy
2. Patients with double cancers
3. Patients having severe allergy
4. Patients with severe organ dysfunction
5. Patients with active infectious disease
6. Pregnancy
7. Patients with severe psychological disease
8. Patients seem inadequate for this study by investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: gemcitabine , cisplatin	Drug: gemcitabine , cisplatin; Dose of gemcitabine and cisplatin and treatment schedule; Other Names: Gemcitabine;gemzer,Cisplatin;Cispulan

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Kansai Hepatobiliary Oncology Group
• Investigators: Study Director: Tetsuo Ajiki, MD, PhD, Kobe University Graduate School of Medicine

Publications and helpful links

General Publications

• Toyoda M, Ajiki T, Fujiwara Y, Nagano H, Kobayashi S, Sakai D, Hatano E, Kanai M, Nakamori S, Miyamoto A, Tsuji A, Kaihara S, Ikoma H, Takemura S, Toyokawa H, Terajima H, Morita S, Ioka T. Phase I study of adjuvant chemotherapy with gemcitabine plus cisplatin in patients with biliary tract cancer undergoing curative resection without major hepatectomy (KHBO1004). Cancer Chemother Pharmacol. 2014 Jun;73(6):1295-301. doi: 10.1007/s00280-014-2431-y. Epub 2014 Mar 11.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (ACTUAL): December 1, 2012
• Study Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: February 7, 2011
• First Submitted That Met QC Criteria: February 15, 2011
• First Posted (ESTIMATE): February 17, 2011

Study Record Updates

• Last Update Posted (ACTUAL): November 17, 2017
• Last Update Submitted That Met QC Criteria: November 13, 2017
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Cisplatin
• Other Study ID Numbers: KHBO1004; UMIN000004622 (REGISTRY: UMIN)