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

Phase 2

Active, not recruiting

• Conditions: Advanced Biliary Tract Cancer
• Interventions: Drug: TS-1; Drug: Gemcitabine; Drug: Nivolumab

• Registration Number: NCT04172402
• Lead Sponsor: National Health Research Institutes, Taiwan

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-11-18
• Study First Submitted QC: 2019-11-19
• Study First Posted: 2019-11-21
• Study Start: 2019-12-27
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-26
• Last Update Posted: 2024-09-30
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 48

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NGS	Nivolumab	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.
NGS	TS-1	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.
NGS	Gemcitabine	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.

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	1 year	To evaluate disease objective response rate (ORR) of nivolumab in combination with gemcitabine and TS1 in patients with advanced biliary tract cancer

Trial Locations

Locations (6)

Chang Gung Memorial Hospital; 🇨🇳 Linkou, Taiwan

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan