GEM/Cisplatin/S-1 vs GEM/Cisplatin for Biliary Tract Cancer

Randomized Phase III Trial Comparing Gemcitabine/Cisplatin/S-1 With Gemcitabine/Cisplatin for Unresectable Biliary Tract Cancer

To validate the superiority of Gemcitabine/Cisplatin/S-1 over Gemcitabine/Cisplatin for unresectable biliary tract cancer.

Study Overview

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

Detailed Description

Gemcitabine/cisplatin combination therapy (GC) has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). Investigators have evaluated the efficacy and safety of gemcitabine/cisplatin/S-1 combination therapy (GCS) for patients with advanced BTC and observed the promising efficacy. In this randomized phase Ⅲ study, investigators aimed to compare GCS with GC in patients with advanced BTC.

• Study Type: Interventional
• Enrollment (Actual): 246
• Phase: Phase 3

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. Performance Status (PS) 0-2
4. No prior history of chemotherapy or radiotherapy.
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 >=45 mL/min)
6. Adequate oral intake
7. 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 with moderate or marked pleural effusion or ascites necessitating drainage
5. Patients with a history of severe drug allergy
6. Patients with other serious comorbid disease
7. Patients who are pregnant or lactating, or have an intention to get pregnant
8. Patients with mental disease

9. Patients who are judged inappropriate for the entry into the study by the principle doctor

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemcitabine/Cisplatin group; Gemcitabine and cisplatin are infused on day1, 8. The cycle is repeated every 3 weeks.	Drug: Gemcitabine/Cisplatin /S-1; 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: Gemcitabine;gemzer, Cisplatin;Cispulan S-1;TS-1,
Experimental: Gemcitabine/Cisplatin /S-1 group; S-1 is given daily for 7 consecutive days and gemcitabine and cisplatin are infused on day1. The cycle is repeated every 2 weeks.	Drug: Gemcitabine/Cisplatin; Gemcitabine and cisplatin are infused on day1, 8. The cycle is repeated every 3 weeks.; Other Names: Gemcitabine;gemzer, Cisplatin;Cispulan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival rate	The primary endpoint is designated to evaluate overall survival rate at 12-month.	Probability of 1-year survival (%)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	The investigators will conduct CT test every 3 months in order to measure the tumor size of each patient and evaluate the best tumor response according to RECIST criteria.	Every 3 months, up to 24 months
Progression free survival	In oredr to research the progression survival, the investigators will check the presence of progression disease for each patient every three months.	Every 3 months, up to 24 months
Number of Participants with Adverse Events as a Measure of Safety	The investigators will examine the frequency and the degree of each side effect that will appear to the patient at each course of chemotherapy .	24 months

Collaborators and Investigators

• Sponsor: Kansai Hepatobiliary Oncology Group
• Investigators: Study Director: Masashi Kanai, Kyoto University

Publications and helpful links

General Publications

• Ioka T, Kanai M, Kobayashi S, Sakai D, Eguchi H, Baba H, Seo S, Taketomi A, Takayama T, Yamaue H, Takahashi M, Sho M, Kamei K, Fujimoto J, Toyoda M, Shimizu J, Goto T, Shindo Y, Yoshimura K, Hatano E, Nagano H; Kansai Hepatobiliary Oncology Group (KHBO). Randomized phase III study of gemcitabine, cisplatin plus S-1 versus gemcitabine, cisplatin for advanced biliary tract cancer (KHBO1401- MITSUBA). J Hepatobiliary Pancreat Sci. 2022 Jul 28. doi: 10.1002/jhbp.1219. Online ahead of print.
• 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 (Actual): July 9, 2014
• Primary Completion (Actual): February 4, 2016
• Study Completion (Actual): April 16, 2018

Study Registration Dates

• First Submitted: June 28, 2014
• First Submitted That Met QC Criteria: July 7, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Actual): February 21, 2019
• Last Update Submitted That Met QC Criteria: February 19, 2019
• Last Verified: April 1, 2018

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: KHBO1401; UMIN 000014371 (Registry Identifier: UMIN)