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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by Kansai Hepatobiliary Oncology Group
Information provided by (Responsible Party):
Kansai Hepatobiliary Oncology Group
ClinicalTrials.gov Identifier:
First received: September 18, 2012
Last updated: April 1, 2015
Last verified: April 2015
To decide maximum tolerated dose and recommended dose of treatment using gemcitabine plus S-1 combination therapy in patients with biliary tract cancer undergoing resection without major hepatectomy

Condition Intervention Phase
Biliary Tract Cancer
Drug: Gemcitabine, S-1
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Adjuvant Chemotherapy With Gemcitabine Plus S-1 in Patients With Biliary Tract Cancer Undergoing Curative Resection Without Major Hepatectomy

Resource links provided by NLM:

Further study details as provided by Kansai Hepatobiliary Oncology Group:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    To establish the maximum tolerated dose of gemcitabine plus S-1 in patients with biliary tract cancer undergoing curative resection without major hepatectomy

Secondary Outcome Measures:
  • Number of Participants with dose limiting toxicity [ Time Frame: At the end of adjuvant chemotherapy (6 months) ] [ Designated as safety issue: Yes ]

    Dose limiting toxicity is defined as follows

    1. Grade 4 neutropenia, thrombocytopenia
    2. Grade 3 or 4 febrile neutropenia
    3. Grade 3 or 4 non-hematological adverse events unless unresponsive to treatment
    4. Any adverse events resulting in interruption of dosing on day 8 in both the two courses
    5. Any adverse events resulting in dose modification or delay of longer than 2 weeks

Estimated Enrollment: 24
Study Start Date: April 2012
Estimated Study Completion Date: March 2017
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: gemcitabine , S-1
Level-2 Gem 800mg/msq, S-1 50mg/msq Level-1 Gem 800mg/msq, S-1 65mg/msq Level 1 Gem 1000mg/msq, S-1 65mg/msq Level 2 Gem 800mg/msq, S-1 80mg/msq
Drug: Gemcitabine, S-1
Dose of gemcitabine and S-1 and treatment schedule
Other Name: Gemcitabine;gemzer , S-1;TS-1

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.

Recently, there are two reports about gemcitabine (GEM) + S-1 combination (GS)chemotherapy after surgical resection for patients with BTC. At Iwate Medical University, Takahara, et al., performed a phase I study using a regimen of repeating 28 days as 1 course. Patients received GEM on day 1 and day 15, and S-1 from day 1 to day 14. The recommended dose is 1,000 mg/m² of GEM and S-1 80 mg/m² after a pancreatoduodenectomy. The 2-year survival rate of the 34 patients that received the GS therapy was 78.6% (Cancer Chemother Pharmacol. 2012 May;69(5):1127-33). At Hiroshima University, a cycle of chemotherapy consisted of intravenous GEM of 700 mg/m² on day 1 and oral S-1 of 50 mg/m² for 7 consecutive days, followed by a 1-week break from chemotherapy (14days as 1 course). Fifty patients received GS therapy and had a significantly better 3-year survival rate (57%) compared with 53 cases of surgery alone (30%). The GS adjuvant chemotherapy was feasible and the adverse event was minimal (Ann Surg. 2009 Dec;250(6):950-6).

Thus, the regimens of these two studies were 14 or 28 days as 1 course. There was no regimen that consisted of GEM on day 1, 8 and S-1 for 14 consecutive days, followed by a 1-week break from chemotherapy (21days as 1 course), which is frequently used for unresectable BTC and pancreatic cancer.

Though a hepatectomy is frequently performed during surgery for BTC, it is unclear if the effect of the anticancer agent is affected by a hepatectomy. Because GEM is metabolized by cytidine deaminase primarily in the liver, the ability to metabolize GEM after a hepatectomy is thought to decrease. Some clinical studies demonstrated that patients who had undergone a hepatectomy could not tolerate the standard dose and schedule of GEM. For adjuvant chemotherapy with GEM, it is necessary to separately examine whether or not the patient has undergone a hepatectomy.

Considering these present conditions, we aimed to assess the safety and efficacy of GEM + S-1 combination chemotherapy (21days as 1 course regimen, which is frequently used for unresectable BTC) for BTC with the patients undergoing curative resection without a hepatectomy.


Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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. PS 0 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01713387

Kansai Medical University Recruiting
Hirakata, Osaka, Japan, 573-1191
Contact: Hideyoshi Toyokawa    +81- 072-804-0101      
Sponsors and Collaborators
Kansai Hepatobiliary Oncology Group
Study Director: Hideyoshi Toyokawa, MD, PhD Kansai Medical University
  More Information

Responsible Party: Kansai Hepatobiliary Oncology Group
ClinicalTrials.gov Identifier: NCT01713387     History of Changes
Other Study ID Numbers: KHBO1202  UMIN000007454 
Study First Received: September 18, 2012
Last Updated: April 1, 2015
Health Authority: Japan: Institutional Review Board

Keywords provided by Kansai Hepatobiliary Oncology Group:
adjuvant chemotherapy

Additional relevant MeSH terms:
Biliary Tract Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Digestive System Neoplasms
Neoplasms by Site
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 26, 2016