A Phase II Trial of Preoperative Chemotherapy for Biliary Tract Cancer (BTC) With Node Metastasis

A Multicenter Phase II Trial of Preoperative Chemotherapy With Gemcitabine/ Cisplatin /S-1 (GCS) for Biliary Tract Cancers With Lymph Node Metastasis Diagnosed by Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)

To evaluate the efficacy and the safety of preoperative chemotherapy with Gemcitabine/ Cisplatin /S-1 for biliary tract cancers with lymph node metastasis by FDG-PET.

Study Overview

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

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 as far advanced stage, which is too late for curative resection, and even if surgery can be performed, the likelihood of relapse is very high. Lymph node metastasis is the most powerful prognostic factor in biliary tract cancer, which makes accurate preoperative assessment of lymph node metastasis important for indication of resection. However, the diagnostic accuracy, sensitivity, and specificity of conventional imaging techniques, including computed tomography (CT) and magnetic resonance imaging (MRI), seem to be insufficient for accurate detection of lymph node metastasis. Previously, the investigators reported FDG-PET is useful for prediction of lymph node metastasis.

On the other hand, gemcitabine has been widely used to treat the patients with unresectable or recurrent biliary tract cancer. In the Advanced Biliary tract Cancer (ABC)-02 study, the first prospective multicenter phase III study in this field, the combination of gemcitabine/cisplatin was compared with gemcitabine monotherapy and found that the combination regimen significantly prolonged Median Survival Time (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.

Furthermore, the investigators reported the safety and efficacy of adding S-1 to gemcitabine/cisplatin combination regimen (GCS) for advanced biliary tract cancer.

In this study, the investigators evaluate the efficacy and the safety of preoperative chemotherapy with Gemcitabine/ Cisplatin /S-1 for biliary tract cancers with lymph node metastasis by FDG-PET

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 2

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 radiologically proven biliary tract cancer.
2. No extra-hepatic disease.
3. No prior therapy.
4. The function of the liver is kept as satisfied after hepatectomy.
5. No chronic liver damage.
6. Patients of age over 20 years.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
8. Sufficient organ function (neutrophil count >=1,500/mm3 and platelet count >=100,000/mm3, Hemoglobin >=9.0g/dL, Aspartate transaminase (AST)/alanine aminotransferase (ALT) <=150 IU/L, total bilirubin <=1.5 mg/dL , creatinine <=1.2 mg/dL , creatinine clearance >=60 mL/min) 9.Patients obtained written informed consent.

Exclusion Criteria:

1. Massive abdominal effusion requiring treatment.
2. Active concomitant malignancy.
3. The case suspected of infection.
4. Patients with water solubility diarrhea.
5. Mental disease or psychotic manifestation.
6. Under continuous steroid therapy.
7. Patients with acute myocardial infarction.
8. Patients with severe complications.
9. Pregnancy or the desire to preserve fecundity.
10. Serious drug hypersensitivity or a history of drug allergy.
11. Any patients judged by the investigator to be unfit to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemcitabine, Cisplatin, S-1; 1000mg/m2/day1, 25mg/m2/day1, 100mg/body/day1-7	Drug: Gemcitabine, Cisplatin, S-1; Preoperative chemotherapy (GCS) 3 cycles -FDG-PET- surgery GCS therapy Gemcitabine 1000mg/m2/day1 Cisplatin 25mg/m2/day1 S-1 100mg/body/day1-7; Other Names: Cisplatin；Cispulan; Gemcitabine；gemzer; S-1；TS-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Curative resection rate	The primary endpoint is designated to evaluate curative resection rate after preoperative chemotherapy with GCS for Biliary Tract Cancers with lymph node metastasis diagnosed by FDG-PET.	14weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate and toxicity	Secondary endpoints include response rate according to FDG-PET and the incidence of adverse events evaluated by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	10 weeks

Collaborators and Investigators

• Sponsor: Kansai Hepatobiliary Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2013
• Primary Completion (Actual): September 27, 2016
• Study Completion (Anticipated): February 1, 2019

Study Registration Dates

• First Submitted: March 22, 2013
• First Submitted That Met QC Criteria: March 28, 2013
• First Posted (Estimate): March 29, 2013

Study Record Updates

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

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: KHBO1201; UMIN000009831 (Registry Identifier: UMIN)