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

NCT ID: NCT04172402

Last Updated: 2025-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-27
• Study Completion Date: 2024-12-31

Brief Summary

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

Detailed Description

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.

Conditions

Advanced Biliary Tract Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NGS

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.

Group Type: EXPERIMENTAL

TS-1

Intervention Type: DRUG

Intervention is administered to patients in this Arm.

Gemcitabine

Intervention Type: DRUG

Intervention is administered to patients in this Arm.

Nivolumab

Intervention Type: DRUG

Intervention is administered to patients in this Arm.

Interventions

TS-1

Intervention is administered to patients in this Arm.

Intervention Type: DRUG

Gemcitabine

Intervention is administered to patients in this Arm.

Intervention Type: DRUG

Nivolumab

Intervention is administered to patients in this Arm.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. histologically confirmed locally advanced or metastatic biliary tract carcinoma (including intrahepatic bile duct, extrahepatic bile duct, gallbladder and ampulla of vater);

2. 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.

3. 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;

4. adequate hematopoietic function which is defined as below:

1. hemoglobin level ≥ 9 g/dL;

2. absolute neutrophil count (ANC) ≥ 1,500/mm3;

3. platelet count ≥ 100,000/mm3;

5. adequate hepatic function which is defined as below:

1. total bilirubin < 2 mg/dL;

2. Alanine aminotransferase (ALT) ≤ 3 x ULN; ≤ 5 x ULN if liver metastasis

6. 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

7. age of 20 years or above;

8. ECOG performance status 0-1;

9. life expectancy of at least 12 weeks;

10. patients with childbearing potential shall have effective contraception for both the patient and his or her partner during the study.

11. ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

1. other malignancy within the past 5 years except for adequately treated basal or squamous cell skin cancer or cervical cancer in situ;

2. history or known presence of brain metastasis;

3. presence of grade 2 or above ascites or pleural effusion;

4. presence of grade 2 or above diarrhea;

5. presence of mental disease or psychotic manifestation;

6. active or uncontrolled infection;

7. significant medical conditions that is contraindicated to study medication or render patient at high risk from treatment complications based on investigator's discretion;

8. pregnant women or nursing mothers, or positive pregnancy test for women of childbearing potential.

9. History of active autoimmune disease within 3 years or long-term use of steroid more than prednisolone 10mg/day.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taipei Veterans General Hospital, Taiwan

OTHER_GOV

Sponsor Role: collaborator

Chang Gung Memorial Hospital

OTHER

Sponsor Role: collaborator

China Medical University Hospital

OTHER

Sponsor Role: collaborator

National Cheng-Kung University Hospital

OTHER

Sponsor Role: collaborator

Kaohsiung Medical University Chung-Ho Memorial Hospital

OTHER

Sponsor Role: collaborator

National Taiwan University Hospital

OTHER

Sponsor Role: collaborator

National Health Research Institutes, Taiwan

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chen Ming-Huang, MD

Role: STUDY_CHAIR

Taipei Veterans General Hospital, Taipei, TAIWAN

Chiang Nai-Jung, MD

Role: PRINCIPAL_INVESTIGATOR

National Health Research Institutes, Taiwan

Locations

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Chang Gung Memorial Hospital

Linkou District, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Countries

Taiwan

References

Chiang NJ, Tang CY, Bai LY, Chang PC, Chen WM, Kang ST, Chen SC, Chen MH, Hsieh JC. Circulating miRNAs as potentially predictive biomarkers for chemoimmunotherapy in advanced biliary tract cancer: a post-hoc analysis of the phase II T1219 study. NPJ Precis Oncol. 2025 Aug 30;9(1):307. doi: 10.1038/s41698-025-01099-x.

Reference Type: DERIVED

PMID: 40885799 (View on PubMed)

Other Identifiers

T1219

Identifier Type: -

Identifier Source: org_study_id