Gemcitabine/Cisplatin/S-1(GCS) Combination Therapy for Patients With Advanced Biliary Tract Cancer

Phase I/II Study of Gemcitabine/Cisplatin/S-1(GCS) Combination Therapy for Patients With Advanced Biliary Tract Cancer

The objective of this study is to evaluate the safety of GCS therapy for phase I and efficacy of GCS therapy for phase II.

Study Overview

• Status: Completed
• Conditions: Biliary Tract Cancer
• Intervention / Treatment: Drug: S-1, Gemcitabine, Cisplatin

Detailed Description

Biliary tract cancer is one of the most lethal malignancies worldwide, with surgery representing the only potentially curative treatment for this disease. However, many patients are diagnosed too late for curative resection, and even if surgery can be performed, the likelihood of relapse is very high. Over the past decade, gemcitabine has been widely used to treat unresectable or recurrent biliary tract cancer patients. In the ABC-02 study, the first prospective multicenter phase III study in this field, gemcitabine/cisplatin combination chemotherapy was compared with gemcitabine monotherapy and found that the combination regimen 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 advanced biliary tract cancer. S-1 is an oral fluoropyrimidine prodrug that has confirmed efficacy against various solid tumors, both alone and in combination with other cytotoxic drugs. S-1 monotherapy has yielded good results against advanced biliary tract cancer and gemcitabine/S-1 combination therapy has yielded promising results with acceptable toxicity levels for patients with advanced biliary tract cancer. In this study, we aimed to determine the safety and efficacy of adding S-1 to gemcitabine/cisplatin combination regimen for advanced biliary tract cancer.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital

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. Patients with cytologically or histologically proved biliary tract cancer 2. age >=20 years 3. PS 0-2 4. No prior history of chemotherapy or radiotherapy. Patients who have undergone adjuvant chemotherapy are eligible if at least 6 months have passed since the last administration.

  5. Adequate bone marrow function (neutrophil count >=1,500/mm3, and platelet count >=100,000/mm3), liver function (total bilirubin >=3 mg/dL and AST/ALT >=150 IU/L), and renal function (creatinine clearance >=60 mL/min) 6.No other serious comorbid disease 7.Adequate oral intake 8.Provided written informed consent

Exclusion Criteria:

• 1. Patients with interstitial pneumonia or pulmonary fibrosis 2. Patients with uncontrollable diabetes mellitus, liver disease, angina pectoris or a new onset of myocardial infarction within 3 months 3. Patients with severe active infection 4. Patients who are pregnant or lactating, or have an intention to get pregnant 5. Patients with a history of severe drug allergy 6. Patients with other serious comorbid disease 7. Patients with mental disease 8. Patients who are judged inappropriate for the entry into the study by the principle doctor 9. Patients with watery diarrhea

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: S-1, Gemcitabine, Cisplatin	Drug: S-1, Gemcitabine, Cisplatin; S-1 is given daily for 7 consecutive days and gemcitabine and cisplatin are infused on day1. The cycle is repeated every 2 weeks.; Other Names: S-1;TS-1, Gemcitabine;gemzer, Cisplatin;Cispulan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
one year survival rate	The primary endpoint is designated to evaluate overall survival rate at 12-month. Secondary endpoints include response rate according to RECIST 1.1 and the incidence of adverse events evaluated by CTCAE v 4.0.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity and response rate	2 years

Collaborators and Investigators

• Sponsor: Kansai Hepatobiliary Oncology Group

Publications and helpful links

General Publications

• Kanai M, Hatano E, Kobayashi S, Fujiwara Y, Marubashi S, Miyamoto A, Shiomi H, Kubo S, Ikuta S, Yanagimoto H, Terajima H, Ikoma H, Sakai D, Kodama Y, Seo S, Morita S, Ajiki T, Nagano H, Ioka T. A multi-institution phase II study of gemcitabine/cisplatin/S-1 (GCS) combination chemotherapy for patients with advanced biliary tract cancer (KHBO 1002). Cancer Chemother Pharmacol. 2015 Feb;75(2):293-300. doi: 10.1007/s00280-014-2648-9. Epub 2014 Dec 5.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2013

Study Registration Dates

• First Submitted: January 3, 2011
• First Submitted That Met QC Criteria: January 25, 2011
• First Posted (ESTIMATE): January 27, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): July 1, 2014
• Last Update Submitted That Met QC Criteria: June 29, 2014
• 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: KHBO1002; UMIN000004468 (REGISTRY: UMIN)