NGS as the First-line Treatment in Advanced Biliary Tract Cancer

Study Overview
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Brief Summary
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To evaluate disease objective response rate (ORR) of nivolumab in combination with gemcitabine and TS1 in patients with advanced biliary tract cancer

Detailed Description
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The primary endpoint will be evaluating overall response rate (ORR) of nivolumab in combination with gemcitabine and TS-1 in patients with advanced BTC. Simon's two-stage design will be used. If there are 3 or fewer subjects with controlled disease in these 19 patients, the study will be stopped. Otherwise, 25 additional patients will be accrued for a total of 44. The null hypothesis will be rejected if 11 or more subjects with controlled disease are observed in 44 patients.

Official Title
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A Study of Nivolumab Combination Gemcitabine and S1 as the First-Line Treatment in Patients With Advanced Biliary Tract Cancer

Conditions
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Advanced Biliary Tract Cancer

Intervention / Treatment
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* Drug: TS-1
* Drug: Gemcitabine
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed locally advanced or metastatic biliary tract carcinoma (including intrahepatic bile duct, extrahepatic bile duct, gallbladder and ampulla of vater); no history of chemotherapy or radiotherapy for biliary tract cancer, except those delivered as adjuvant setting that completed at least 6 months before documentation of recurrence by imaging study. presence of at least one measurable tumor lesion which is defined as lesions that can be accurately measured in at least 1 dimension with longest diameter (LD) ≥20 mm using conventional techniques or ≥10 mm with spiral CT and MRI; measurable lymph nodes must be ≥15 mm in the short axis; adequate hematopoietic function which is defined as below: hemoglobin level ≥ 9 g/dL; absolute neutrophil count (ANC) ≥ 1,500/mm3; platelet count ≥ 100,000/mm3; adequate hepatic function which is defined as below: total bilirubin < 2 mg/dL; Alanine aminotransferase (ALT) ≤ 3 x ULN; ≤ 5 x ULN if liver metastasis adequate renal function: creatinine clearance rate (CCr) ≥ 50 mL/min ((based upon Cockroft-Gault formula or 24-hour urine collection); < Cockroft-Gault formula > Male: ((140 - age) × weight [kg])/(72 × serum creatinine[mg/dL]) Female: 0.85 x estimate for male age of 20 years or above; ECOG performance status 0-1; life expectancy of at least 12 weeks; patients with childbearing potential shall have effective contraception for both the patient and his or her partner during the study. ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: other malignancy within the past 5 years except for adequately treated basal or squamous cell skin cancer or cervical cancer in situ; history or known presence of brain metastasis; presence of grade 2 or above ascites or pleural effusion; presence of grade 2 or above diarrhea; presence of mental disease or psychotic manifestation; active or uncontrolled infection; significant medical conditions that is contraindicated to study medication or render patient at high risk from treatment complications based on investigator's discretion; pregnant women or nursing mothers, or positive pregnancy test for women of childbearing potential. History of active autoimmune disease within 3 years or long-term use of steroid more than prednisolone 10mg/day.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Advanced Biliary Tract Cancer
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NGS<br>Eligible patients will receive Nivolumab 240mg on day 1, gemcitabine 800 mg/m2/day on day 1 and S-1 orally 80-120 mg/day (depending on patient's body surface area (BSA)) on day 1 to 10 in a 2-week cycle. BSA < 1.25 m2: 80 mg/day 1.25 m2 ≤ BSA < 1.5 m2: 100 mg/day BSA ≥ 1.5 m2: 120 mg/day The treatment will be administered until disease progression, intolerable toxicity, or consent withdrawal during any time of the study. | Drug: TS-1<br>* Intervention is administered to patients in this Arm.<br>Drug: Gemcitabine<br>* Intervention is administered to patients in this Arm.<br>Drug: Nivolumab<br>* Intervention is administered to patients in this Arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | To evaluate disease objective response rate (ORR) of nivolumab in combination with gemcitabine and TS1 in patients with advanced biliary tract cancer | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Biliary Tract Cancer, Nivolumab, Phase 2