Circulating Tumor DNA Guided Adjuvant Chemotherapy for Biliary Tract Carcinoma

Study Overview
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Brief Summary
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In recent years, circulating tumor DNA (ctDNA)had achieved encouraging results in monitoring recurrence and metastasis after surgery, and has potential clinical application value. The presence of ctDNA after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood.

Detailed Description
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The results of the PRODIGE-12/ACCORD-18 study showed that, with a median follow-up of 47 months, the adjuvant chemotherapy arm did not lead to a significant improvement in recurrence-free survival (RFS) and overall survival (OS). Notably, the patients with gallbladder cancer experienced adjuvant chemotherapy significantly worse RFS and OS compared to those in the monitoring arm. ctDNA risk stratifies patients to guide adjuvant treatment decisions This study aimed to demonstrate that a escalation strategy of ctDNA guided adjuvant chemotherapy is superior to standard of care treatment as measured by 2 year disease free survival (DFS) in patients with stage II- III biliary tract cancers with minimal residual disease (MRD) (ctDNA positive).

Official Title
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Circulating Tumor DNA Guided Adjuvant Chemotherapy for Biliary Tract Carcinoma: A Prospective Clinical Trial

Conditions
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Biliary Tract Cancer

Intervention / Treatment
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* Drug: S-1(Intravenous combined with oral)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Patients with pathologically confirmed BTCs according to the UICC/AJCC TNM staging system (8th edition 2017) for stage II-III tumours. Patients eligible for radical resection of BTCs. No synchronous or metastatic malignant tumour found in other organs other than the primary tumor. 2) Personal status (PS) score as over 80 or Eastern Cooperative Oncology Group (ECOG) score as 0   2. 3）With expected survival of more than 12 months. 4) Radical operation performed. Exclusion Criteria: 1) Patients with positive surgical margins and residual lesions after biliary tract tumor surgery. 2) Blood transfusion performed during operation or within 2 weeks before operation. 3) Have a history of other malignant tumors within 5 years.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Group 1: Patients testing negative for ctDNA treated using standard of care treatment<br>Postoperative ctDNA-negative patients receive oral Teysuno (S-1) for adjuvant therapy。 | |
| Experimental: Group 2: Patients with a positive ctDNA test are treated with an escalation strategy<br>Postoperative ctDNA-positive patients receive intravenous combined oral Teysuno (S-1) for adjuvant therapy。 | Drug: S-1(Intravenous combined with oral)<br>* Oral combined with intravenous S-1 for ctDNA-positive patients (escalating treatment strategy)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ctDNA guided adjuvant chemotherapy versus Translational sub study | To demonstrate the superiority of an escalation strategy of ctDNA-guided adjuvant chemotherapy over standard-of-care treatment, 2-year disease-free survival (DFS) was measured as 2-year Disease-Free Survival (DFS) in high-risk stage II-III BTC patients with no evidence of minimal residual disease (ctDNA-negative). | Up to 60 months | 
| Sensitivity of postoperative ctDNA in monitoring recurrence and metastasis | Number of patients with ctDNA positive and imaging confirmed recurrence or metastasis / number of all imaging confirmed recurrence or metastasis | Up to 60 months | 
| Specificity of postoperative ctDNA in monitoring recurrence and metastasis | Number of patients with ctDNA negative and no recurrence and metastasis confirmed by imaging / number of patients with no recurrence and metastasis confirmed by imaging | Up to 60 months | 
| Accuracy of postoperative ctDNA in monitoring recurrence and metastasis | True positive/ctDNA-positive samples | Up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival (OS) | Overall survival of included patients | From date of randomization until the date of first documented date of death from any cause, assessed up to 60 months. | 
| ctDNA clearance rate | The rate of ctDNA positive before chemotherapy that turns negative after adjuvant chemotherapy | Up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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S-1, circulating tumor DNA (ctDNA)